Patent Publication Number: US-2020291120-A1

Title: Anti-clec2d antibodies and methods of use thereof

Description:
RELATED APPLICATION 
     This application claims priority to and the benefit of Indian Provisional Patent Application No. 201941005395, filed on Feb. 11, 2019, the entire contents of which are incorporated herein by reference. 
     INCORPORATION-BY-REFERENCE OF SEQUENCE LISTING 
     The contents of the text file named ZMTR-001_001US Seq_List_ST25 which was created on Apr. 21, 2020, and is 3.518 megabytes in size, are incorporated herein by reference in their entirety. 
     TECHNICAL FIELD 
     The present disclosure relates to immunology, especially immune-oncology. Particularly, this disclosure relates to novel antibody molecules against CLEC2D antigen. This disclosure also relates to multiple formats and amino acid compositions of the disclosed antibody molecules, variable regions of the heavy and light chains of the antibody molecules, and CDR composition and length distribution against CLEC2D antigen. The compositions of this disclosure can be used either as monotherapies or in combination with other antibody molecules or any other therapeutic agents that are relevant for the treatment or prevention of diseases, such as cancer. 
     BACKGROUND 
     Modulation of immune cell checkpoint receptors via antibody-based/directed therapeutic approaches has been gaining constant interest over the last decade. Many of these receptors are involved in T cell checkpoint modulation. However, B cell, natural killer (NK) cell, and myeloid cell checkpoint modulation is attracting attention. 
     NK cells are part of the innate immunity which recognize and induce cytotoxicity against a wide range of target cells, such as tumor cells or virus infected cells. In addition, NK cells participate in the initiation and progress of the adaptive immune response through the production of various cytokines. Usually, these responses are regulated by the interaction of a wide array of activating and inhibitory receptors with ligands on the surface of the target cells and immune cells. 
     The NK cell receptors are divided into two main structural classes: the immunoglobulin and C-type lectin-like (CTL) superfamilies. The NKR-P1 receptors (e.g., CD161) are a family of C-type lectin-like transmembrane molecules that are important immuno-regulatory genes and are expressed on various cell types, including spleen dendritic cells, subsets of T cells and granulocytes. The Lectin-Like Transcript 1 (LLT1) or C-Type Lectin Domain Family 2 Member D (CLEC2D) or osteoclast inhibitory lectin (OCIL) molecule is a ligand for the CD161 receptor and this interaction differentially regulates the NK cell and T cell function. There are six splice variants of CLEC2D, isoform 1 being the canonical sequence which is expressed on NK cells, T cells, monocytes/macrophages, activated B cells and dendritic cells, and functions as a human NK cell activating receptor. The polypeptide chain of CLEC2D can be divided into the N-terminal cytoplasmic part, trans-membrane and stalk regions and C-terminal CTL ectodomain with two predicted N-glycosylation sites. 
     CLEC2D and CD161 interaction leads to escape from the host defense in several disease scenarios, including various cancers. Such immune escape has been reported in human glioblastoma and other diseases. Moreover, CLEC2D expression on B cells is thought to regulate cross-talk between NK cells and antigen presenting cells (APC). Blocking CLEC2D-CD161 interaction therefore provides a new therapeutic option for the treatment of various cancers. 
     The downstream signaling of CLEC2D-CD161 interactions is poorly understood. The interaction of CLEC2D/CD161 inhibits NK cell functions and stimulates T cell proliferation and secretion of cytokines. Hence, the effects of CLEC2D/CD161 interaction could be reversed by using monoclonal antibodies specifically binding to CLEC2D, and disrupting the interaction between CLEC2D and its known receptor CD161 or other unknown cellular mechanisms. 
     SUMMARY 
     The disclosure provides an isolated antibody or antigen-binding fragment thereof comprising a heavy chain and a light chain, wherein the heavy chain comprises a sequence selected from the group consisting of: (a) a sequence that is at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, at least 99.9% or 100% identical to a sequence selected from SEQ ID NO: 46, SEQ ID NO: 65, SEQ ID NO: 59, and SEQ ID NO: 99; (b) a sequence that is at least 80%, at least 81%, at least 82%, at least 83%, at least 84%, at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, at least 99.9% or 100% identical to a sequence selected from SEQ ID NO: 57, SEQ ID NO: 91, SEQ ID NO: 98, SEQ ID NO: 84, SEQ ID NO: 58, SEQ ID NO: 88, SEQ ID NO: 96, SEQ ID NO: 47, SEQ ID NO: 17, and SEQ ID NO: 8; (c) a sequence that is at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, at least 99.9% or 100% identical to a sequence selected from SEQ ID NO: 93, SEQ ID NO: 53, SEQ ID NO: 95, SEQ ID NO: 23, SEQ ID NO: 103, and SEQ ID NO: 7; (d) a sequence that is at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, at least 99.9% or 100% identical to a sequence selected from SEQ ID NO: 45, SEQ ID NO: 15, SEQ ID NO: 51, SEQ ID NO: 44, SEQ ID NO: 73, SEQ ID NO: 36, SEQ ID NO: 77, SEQ ID NO: 50, and SEQ ID NO: 6; (e) a sequence that is at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5% or at least 99.9% identical or 100% identical to a sequence selected from SEQ ID NO: 97, SEQ ID NO: 16, SEQ ID NO: 76, SEQ ID NO: 9, SEQ ID NO: 89, SEQ ID NO: 107, SEQ ID NO: 68, SEQ ID NO: 29, SEQ ID NO: 67, SEQ ID NO: 74, SEQ ID NO: 32, SEQ ID NO: 81, SEQ ID NO: 106, SEQ ID NO: 31, SEQ ID NO: 62, SEQ ID NO: 48, SEQ ID NO: 75, SEQ ID NO: 12, SEQ ID NO: 102, SEQ ID NO: 54, SEQ ID NO: 80, SEQ ID NO: 26, SEQ ID NO: 30, SEQ ID NO: 92, SEQ ID NO: 108, and SEQ ID NO: 79; (f) a sequence that is at least 45%, at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5% or at least 99.9% identical or 100% identical to a sequence selected from SEQ ID NO: 105, SEQ ID NO: 101, SEQ ID NO: 4, SEQ ID NO: 72, SEQ ID NO: 28, SEQ ID NO: 64, SEQ ID NO: 25, SEQ ID NO: 60, SEQ ID NO: 55, SEQ ID NO: 52, SEQ ID NO: 27, SEQ ID NO: 43, SEQ ID NO: 70, SEQ ID NO: 71, SEQ ID NO: 14, SEQ ID NO: 85, SEQ ID NO: 13, SEQ ID NO: 61, SEQ ID NO: 42, SEQ ID NO: 39, SEQ ID NO: 10, SEQ ID NO: 49, SEQ ID NO: 24, SEQ ID NO: 40, SEQ ID NO: 63, SEQ ID NO: 78, SEQ ID NO: 2, SEQ ID NO: 94, and SEQ ID NO: 5; (g) a sequence that is at least 40%, at least 45%, at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5% or at least 99.9% identical or 100% identical to a sequence selected from SEQ ID NO: 11, SEQ ID NO: 35, SEQ ID NO: 86, SEQ ID NO: 22, SEQ ID NO: 69, SEQ ID NO: 41, SEQ ID NO: 3, SEQ ID NO: 66, SEQ ID NO: 37, SEQ ID NO: 56, SEQ ID NO: 21, SEQ ID NO: 38, SEQ ID NO: 90, SEQ ID NO: 100, SEQ ID NO: 18, SEQ ID NO: 20, SEQ ID NO: 83, SEQ ID NO: 1, and SEQ ID NO: 19; and (h) a sequence that is at least 35%, at least 40%, at least 45%, at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5% or at least 99.9% identical or 100% identical to a sequence selected from SEQ ID NO: 33, SEQ ID NO: 34, SEQ ID NO: 87, SEQ ID NO: 82, and SEQ ID NO: 104, wherein the antibody or antigen-binding fragment thereof binds to C-Type Lectin Domain Family 2 Member D (CLEC2D). 
     The disclosure provides isolated antibodies or antigen-binding fragments thereof comprising a heavy chain and a light chain, wherein the light chain comprises a sequence selected from the group consisting of: (a) sequence that is at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, at least 99.9% or 100% identical to a sequence selected from SEQ ID NO: 218, SEQ ID NO: 249, SEQ ID NO: 230, SEQ ID NO: 279, SEQ ID NO: 316, SEQ ID NO: 237, SEQ ID NO: 322, SEQ ID NO: 225, SEQ ID NO: 318, SEQ ID NO: 233, SEQ ID NO: 305, SEQ ID NO: 280, SEQ ID NO: 283, SEQ ID NO: 242, SEQ ID NO: 286, SEQ ID NO: 297, SEQ ID NO: 309, and SEQ ID NO: 246; (b) a sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, at least 99.9% or 100% identical to a sequence selected from SEQ ID NO: 222, SEQ ID NO: 258, SEQ ID NO: 219, SEQ ID NO: 313, SEQ ID NO: 294, SEQ ID NO: 303, SEQ ID NO: 317, SEQ ID NO: 273, SEQ ID NO: 266, SEQ ID NO: 315, SEQ ID NO: 257, SEQ ID NO: 288, SEQ ID NO: 301, SEQ ID NO: 221, SEQ ID NO: 240, SEQ ID NO: 299, SEQ ID NO: 247, SEQ ID NO: 263, and SEQ ID NO: 274; (c) a sequence that is at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, at least 99.9% or 100% identical to a sequence selected from SEQ ID NO: 231, SEQ ID NO: 250, SEQ ID NO: 260, SEQ ID NO: 226, SEQ ID NO: 271, SEQ ID NO: 256, SEQ ID NO: 272, SEQ ID NO: 278, SEQ ID NO: 302, SEQ ID NO: 320, SEQ ID NO: 295, SEQ ID NO: 292, SEQ ID NO: 229, SEQ ID NO: 264, SEQ ID NO: 252, SEQ ID NO: 267, SEQ ID NO: 304, SEQ ID NO: 300, SEQ ID NO: 311, and SEQ ID NO: 324; (d) a sequence that is at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, at least 99.9% or 100% identical to a sequence selected from SEQ ID NO: 259, SEQ ID NO: 239, SEQ ID NO: 281, SEQ ID NO: 228, SEQ ID NO: 217, SEQ ID NO: 227, and SEQ ID NO: 251; (e) a sequence that is at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, at least 99.9% or 100% identical to a sequence selected from SEQ ID NO: 307, SEQ ID NO: 262, SEQ ID NO: 253, SEQ ID NO: 276, SEQ ID NO: 323, SEQ ID NO: 234, SEQ ID NO: 261, SEQ ID NO: 312, and SEQ ID NO: 290; (f) a sequence that is at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, at least 99.9% or 100% identical to a sequence selected from SEQ ID NO: 254, SEQ ID NO: 289, SEQ ID NO: 238, SEQ ID NO: 268, SEQ ID NO: 248, SEQ ID NO: 284, SEQ ID NO: 244, SEQ ID NO: 310, SEQ ID NO: 243, SEQ ID NO: 285, SEQ ID NO: 220, SEQ ID NO: 255, SEQ ID NO: 293, SEQ ID NO: 298, SEQ ID NO: 235, SEQ ID NO: 319, SEQ ID NO: 245, SEQ ID NO: 224, SEQ ID NO: 291, SEQ ID NO: 277, and SEQ ID NO: 232; and (g) a sequence that is at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, at least 99.9% or 100% identical to a sequence selected from SEQ ID NO: 282, SEQ ID NO: 308, SEQ ID NO: 287, SEQ ID NO: 321, SEQ ID NO: 236, SEQ ID NO: 265, SEQ ID NO: 270, SEQ ID NO: 275, SEQ ID NO: 306, SEQ ID NO: 296, SEQ ID NO: 241, SEQ ID NO: 314, and SEQ ID NO: 223; wherein the antibody or antigen-binding fragment thereof binds to CLEC2D. 
     The disclosure provides isolated antibodies or antigen-binding fragments thereof, comprising: (a) a heavy chain comprising a sequence selected from: (i) a sequence that is at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, at least 99.9% or 100% identical to a sequence selected from SEQ ID NO: 46, SEQ ID NO: 65, SEQ ID NO: 59, and SEQ ID NO: 99; (ii) a sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, at least 99.9% or 100% identical to a sequence selected from SEQ ID NO: 57, SEQ ID NO: 91, SEQ ID NO: 98, SEQ ID NO: 84, SEQ ID NO: 58, SEQ ID NO: 88, SEQ ID NO: 96, SEQ ID NO: 47, SEQ ID NO: 17, and SEQ ID NO: 8; (iii) a sequence that is at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, at least 99.9% or 100% identical to a sequence selected from SEQ ID NO: 93, SEQ ID NO: 53, SEQ ID NO: 95, SEQ ID NO: 23, SEQ ID NO: 103, and SEQ ID NO: 7; (iv) a sequence that is at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, at least 99.9% or 100% identical to a sequence selected from SEQ ID NO: 45, SEQ ID NO: 15, SEQ ID NO: 51, SEQ ID NO: 44, SEQ ID NO: 73, SEQ ID NO: 36, SEQ ID NO: 77, SEQ ID NO: 50, and SEQ ID NO: 6; (v) a sequence that is at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, at least 99.9% or 100% identical to a sequence selected from SEQ ID NO: 97, SEQ ID NO: 16, SEQ ID NO: 76, SEQ ID NO: 9, SEQ ID NO: 89, SEQ ID NO: 107, SEQ ID NO: 68, SEQ ID NO: 29, SEQ ID NO: 67, SEQ ID NO: 74, SEQ ID NO: 32, SEQ ID NO: 81, SEQ ID NO: 106, SEQ ID NO: 31, SEQ ID NO: 62, SEQ ID NO: 48, SEQ ID NO: 75, SEQ ID NO: 12, SEQ ID NO: 102, SEQ ID NO: 54, SEQ ID NO: 80, SEQ ID NO: 26, SEQ ID NO: 30, SEQ ID NO: 92, SEQ ID NO: 108, and SEQ ID NO: 79; (vi) a sequence that is at least 45%, at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, at least 99.9% or 100% identical to a sequence selected from SEQ ID NO: 105, SEQ ID NO: 101, SEQ ID NO: 4, SEQ ID NO: 72, SEQ ID NO: 28, SEQ ID NO: 64, SEQ ID NO: 25, SEQ ID NO: 60, SEQ ID NO: 55, SEQ ID NO: 52, SEQ ID NO: 27, SEQ ID NO: 43, SEQ ID NO: 70, SEQ ID NO: 71, SEQ ID NO: 14, SEQ ID NO: 85, SEQ ID NO: 13, SEQ ID NO: 61, SEQ ID NO: 42, SEQ ID NO: 39, SEQ ID NO: 10, SEQ ID NO: 49, SEQ ID NO: 24, SEQ ID NO: 40, SEQ ID NO: 63, SEQ ID NO: 78, SEQ ID NO: 2, SEQ ID NO: 94, and SEQ ID NO: 5; (vii) a sequence that is at least 40%, at least 45%, at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, at least 99.9% or 100% identical to a sequence selected from SEQ ID NO: 11, SEQ ID NO: 35, SEQ ID NO: 86, SEQ ID NO: 22, SEQ ID NO: 69, SEQ ID NO: 41, SEQ ID NO: 3, SEQ ID NO: 66, SEQ ID NO: 37, SEQ ID NO: 56, SEQ ID NO: 21, SEQ ID NO: 38, SEQ ID NO: 90, SEQ ID NO: 100, SEQ ID NO: 18, SEQ ID NO: 20, SEQ ID NO: 83, SEQ ID NO: 1, and SEQ ID NO: 19; and (viii) a sequence that is at least 35%, at least 40%, at least 45%, at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, at least 99.9% or 100% identical to a sequence selected from SEQ ID NO: 33, SEQ ID NO: 34, SEQ ID NO: 87, SEQ ID NO: 82, and SEQ ID NO: 104; and (b) a light chain comprising a sequence selected from: (i) a sequence that is at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, at least 99.9% or 100% identical to a sequence selected from SEQ ID NO: 218, SEQ ID NO: 249, SEQ ID NO: 230, SEQ ID NO: 279, SEQ ID NO: 316, SEQ ID NO: 237, SEQ ID NO: 322, SEQ ID NO: 225, SEQ ID NO: 318, SEQ ID NO: 233, SEQ ID NO: 305, SEQ ID NO: 280, SEQ ID NO: 283, SEQ ID NO: 242, SEQ ID NO: 286, SEQ ID NO: 297, SEQ ID NO: 309, and SEQ ID NO: 246; (ii) a sequence that is at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, at least 99.9% or 100% identical to a sequence selected from SEQ ID NO: 222, SEQ ID NO: 258, SEQ ID NO: 219, SEQ ID NO: 313, SEQ ID NO: 294, SEQ ID NO: 303, SEQ ID NO: 317, SEQ ID NO: 273, SEQ ID NO: 266, SEQ ID NO: 315, SEQ ID NO: 257, SEQ ID NO: 288, SEQ ID NO: 301, SEQ ID NO: 221, SEQ ID NO: 240, SEQ ID NO: 299, SEQ ID NO: 247, SEQ ID NO: 263, and SEQ ID NO: 274; (iii) a sequence that is at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, at least 99.9% or 100% identical to a sequence selected from SEQ ID NO: 231, SEQ ID NO: 250, SEQ ID NO: 260, SEQ ID NO: 226, SEQ ID NO: 271, SEQ ID NO: 256, SEQ ID NO: 272, SEQ ID NO: 278, SEQ ID NO: 302, SEQ ID NO: 320, SEQ ID NO: 295, SEQ ID NO: 292, SEQ ID NO: 229, SEQ ID NO: 264, SEQ ID NO: 252, SEQ ID NO: 267, SEQ ID NO: 304, SEQ ID NO: 300, SEQ ID NO: 311, and SEQ ID NO: 324; (iv) a sequence that is at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, at least 99.9% or 100% identical to a sequence selected from SEQ ID NO: 259, SEQ ID NO: 239, SEQ ID NO: 281, SEQ ID NO: 228, SEQ ID NO: 217, SEQ ID NO: 227, and SEQ ID NO: 251; (v) a sequence that is at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, at least 99.9% or 100% identical to a sequence selected from SEQ ID NO: 307, SEQ ID NO: 262, SEQ ID NO: 253, SEQ ID NO: 276, SEQ ID NO: 323, SEQ ID NO: 234, SEQ ID NO: 261, SEQ ID NO: 312, and SEQ ID NO: 290; (vi.) a sequence that is at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, at least 99.9% or 100% identical to a sequence selected from SEQ ID NO: 254, SEQ ID NO: 289, SEQ ID NO: 238, SEQ ID NO: 268, SEQ ID NO: 248, SEQ ID NO: 284, SEQ ID NO: 244, SEQ ID NO: 310, SEQ ID NO: 243, SEQ ID NO: 285, SEQ ID NO: 220, SEQ ID NO: 255, SEQ ID NO: 293, SEQ ID NO: 298, SEQ ID NO: 235, SEQ ID NO: 319, SEQ ID NO: 245, SEQ ID NO: 224, SEQ ID NO: 291, SEQ ID NO: 277, and SEQ ID NO: 232; and (vii) a sequence that is at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, at least 99.9% or 100% identical to a sequence selected from SEQ ID NO: 282, SEQ ID NO: 308, SEQ ID NO: 287, SEQ ID NO: 321, SEQ ID NO: 236, SEQ ID NO: 265, SEQ ID NO: 270, SEQ ID NO: 275, SEQ ID NO: 306, SEQ ID NO: 296, SEQ ID NO: 241, SEQ ID NO: 314, and SEQ ID NO: 223; wherein the antibody or antigen-binding fragment thereof binds to CLEC2D. 
     The disclosure provides isolated antibodies or antigen-binding fragments thereof comprising a heavy chain and a light chain, wherein the heavy chain comprises a sequence selected from any one of SEQ ID NOs: 1-108. 
     The disclosure provides isolated antibodies or antigen-binding fragments thereof comprising a heavy chain and a light chain, wherein the light chain comprises a sequence selected from any one of SEQ ID NOs: 217-324. 
     The disclosure provides isolated antibodies or antigen-binding fragments thereof comprising a heavy chain and a light chain, wherein the heavy chain comprises a sequence selected from any one of SEQ ID NOs: 1-108, and the light chain comprises a sequence selected from any one of SEQ ID NOs: 217-324. 
     The disclosure provides isolated antibodies or antigen-binding fragments thereof comprising a heavy chain and a light chain, wherein the heavy chain comprises: (i) a heavy chain (HC) CDR1 comprising a sequence selected from SEQ ID NOs: 433-485; (ii) an HC CDR2 comprising a sequence selected from SEQ ID NOs: 486-546; and (iii) an HC CDR3 comprising a sequence selected from SEQ ID NOs: 547-653, wherein the antibody or antigen-binding fragment thereof binds to CLEC2D. 
     The disclosure provides isolated antibodies or antigen-binding fragments thereof comprising a heavy chain and a light chain, wherein the light chain comprises: (i) a light chain (LC) CDR1 comprising a sequence selected from SEQ ID NOs: 654-726; (ii) an LC CDR2 comprising a sequence selected from SEQ ID NOs: 727-783; and (iii) an LC CDR3 comprising a sequence selected from SEQ ID NOs: 784-885; wherein the antibody or antigen-binding fragment thereof binds to CLEC2D. 
     The disclosure provides isolated antibodies or antigen-binding fragments thereof, comprising: a heavy chain comprising an HC CDR1 sequence selected from SEQ ID NOs: 433-485, an HC CDR2 sequence selected from SEQ ID NOs: 486-546, and an HC CDR3 sequence selected from SEQ ID NOs: 547-653; a light chain comprising a LC CDR1 sequence selected from SEQ ID NOs: 654-726, a LC CDR2 sequence selected from SEQ ID NOs: 727-783, and a LC CDR3 sequence selected from SEQ ID NOs: 784-885; or a combination thereof. 
     In some embodiments of the antibodies or antigen binding fragments thereof of the disclosure, the antibody or antigen-binding fragment thereof binds to: a human CLEC2D polypeptide comprising a sequence selected from SEQ ID NOs: 886-909; a human CLEC2D polypeptide comprising a sequence selected from SEQ ID NOs: 930-1003; a cynomolgus CLEC2D polypeptide comprising a sequence selected from SEQ ID NOs: 918-920; a mouse CLEC2D polypeptide comprising a sequence selected from SEQ ID NOs: 911-915; a rat CLEC2D polypeptide comprising a sequence of SEQ ID NO: 910; and/or a dog CLEC2D polypeptide comprising a sequence selected from SEQ ID NOs: 916-917. 
     The disclosure provides an isolated antibody or antigen-binding fragment thereof, comprising a heavy chain and a light chain, wherein the heavy chain comprises a heavy chain complementarity determining region (CDRH) 1, CDRH2 and CDRH3 amino acid sequence of an anti-CLEC2D antibody selected from the group consisting of: A1, B1, E1, P1, U1, Y1, E2, I2 and L2, as disclosed in Table 9A, and wherein the light chain comprises a light chain complementarity determining region (CDRL)1, CDRL2 and CDRL3 amino acid sequence of an anti-CLEC2D antibody selected from the group consisting of: A1, B1, E1, P1, U1, Y1, E2, I2 and L2, as disclosed in Table 9A. 
     The disclosure provides an isolated antibody or antigen-binding fragment thereof, comprising a heavy chain and a light chain, wherein the heavy chain comprises a variable heavy chain amino acid sequence of an anti-CLEC2D antibody selected from the group consisting of: A1, B1, E1, P1, U1, Y1, E2, I2 and L2, as disclosed in Table 9A, and wherein the light chain comprises a variable light chain amino acid sequence of an anti-CLEC2D antibody selected from the group consisting of: A1, B1, E1, P1, U1, Y1, E2, I2 and L2, as disclosed in Table 9A. 
     The disclosure provides an isolated antibody or antigen-binding fragment thereof, comprising a heavy chain and a light chain, wherein the heavy chain comprises a heavy chain frame work region sequence of a Germline family of an anti-CLEC2D antibody selected from the group consisting of: A1, B1, E1, P1, U1, Y1, E2, I2 and L2, of Table 9B, as disclosed herein, and wherein the light chain comprises a frame work region sequence of a light chain Germline family of an anti-CLEC2D antibody selected from the group consisting of: A1, B1, E1, P1, U1, Y1, E2, I2 and L2, of Table 9B, as disclosed herein. 
     In some embodiments of the antibodies or antigen binding fragments thereof of the disclosure, the antibody or antigen-binding fragment thereof is a monoclonal antibody. 
     In some embodiments of the antibodies or antigen binding fragments thereof of the disclosure, the antibody or antigen-binding fragment thereof blocks binding of CLEC2D to a receptor. In some embodiments, the receptor comprises a CD161 receptor, and the CD161 receptor comprises a sequence selected from SEQ ID NOs: 921-929. 
     In some embodiments of the antibodies or antigen binding fragments thereof of the disclosure, the antibody or antigen-binding fragment thereof is human, murine or chimeric. In some embodiments, the antigen-binding fragment is selected from the group consisting of Fv, Fav, F(ab′)2, Fab′, dsFv, scFv, sc(Fv)2, scFv-CH3, scFv-Fc, and diabody fragments. In some embodiments, the antibody or antigen-binding fragment thereof binds to human CLEC2D with an affinity (KD) of less than 100 nM. 
     The disclosure provides pharmaceutical compositions comprising peptides (e.g., antibodies or antigen-binding fragments thereof) or nucleic acids described in the disclosure. 
     The disclosure provides pharmaceutical compositions comprising antibodies or antigen-binding fragments thereof of the disclosure. 
     The disclosure provides pharmaceutical compositions comprising nucleic acids encoding the antibodies or antigen-binding fragments thereof of the disclosure. 
     In some embodiments of the pharmaceutical compositions of the disclosure, the pharmaceutical composition further comprises at least one of a buffer, a pharmaceutically acceptable diluent, a carrier, a solubilizer, an emulsifier, and a preservative. 
     The disclosure provides isolated nucleic acids comprising a polynucleotide sequence that encodes an amino acid heavy chain sequence selected from SEQ ID NOs: 109-216. 
     The disclosure provides isolated nucleic acids comprising a polynucleotide sequence that encodes an amino acid light chain sequence selected from SEQ ID NOs: 325-432. 
     The disclosure provides an isolated nucleic acid, comprising a polynucleotide sequence that encodes a heavy chain comprising a CDRH1, CDRH2 and CDRH3 amino acid sequence according to the CDRH1, CDRH2 and CDRH3 amino acid sequence respectively, of an anti-CLEC2D antibody selected from the group consisting of: A1, B1, E1, P1, U1, Y1, E2, I2 and L2, of Table 9A, as disclosed herein. 
     The disclosure provides an isolated nucleic acid, comprising a polynucleotide sequence that encodes a light chain comprising a CDRL1, CDRL2 and CDRL3 amino acid sequence according to the CDRL1, CDRL2 and CDRL3 amino acid sequence respectively, of an anti-CLEC2D antibody selected from the group consisting of: A1, B1, E1, P1, U1, Y1, E2, I2 and L2, of Table 9A, as disclosed herein. 
     The disclosure provides an isolated nucleic acid, comprising a polynucleotide sequence that encodes a heavy chain amino acid sequence according to variable heavy chain amino acid sequence of an anti-CLEC2D antibody antibody selected from the group consisting of: A1, B1, E1, P1, U1, Y1, E2, I2 and L2, of Table 9A, as disclosed herein. 
     The disclosure provides an isolated nucleic acid, comprising a polynucleotide sequence that encodes a light chain amino acid sequence according to variable light chain amino acid sequence of an anti-CLEC2D antibody selected from the group consisting of: A1, B1, E1, P1, U1, Y1, E2, I2 and L2, of Table 9A, as disclosed herein. 
     The disclosure provides an isolated nucleic acid, comprising a polynucleotide sequence that encodes a heavy chain comprising a framework region amino acid sequence according to heavy chain framework region amino acid sequence of an anti-CLEC2D antibody selected from the group consisting of: A1, B1, E1, P1, U1, Y1, E2, I2 and L2, of Table 9B, as disclosed herein. 
     The disclosure provides an isolated nucleic acid comprising a polynucleotide sequence that encodes a light chain comprising a framework region amino acid sequence according to light chain framework region amino acid sequence of an anti-CLEC2D antibody selected from the group consisting of: A1, B1, E1, P1, U1, Y1, E2, I2 and L2, of Table 9B, as disclosed herein. 
     The disclosure provides isolated nucleic acids comprising a polynucleotide sequence that encodes a heavy chain amino acid sequence of an antibody or antigen binding fragment thereof of the disclosure. 
     The disclosure provides isolated nucleic acids comprising a polynucleotide sequence that encodes a light chain amino acid sequence of an antibody or antigen binding fragment thereof of the disclosure. 
     The disclosure provides compositions comprising a first nucleic acid that encodes a polypeptide selected from SEQ ID NOs: 109-216 and a second nucleic acid that encodes a polypeptide selected from SEQ ID NOs: 325-432. 
     The disclosure provides vectors comprising the nucleic acids of the disclosure. 
     The disclosure provides cells comprising the nucleic acids, nucleic acid compositions or vectors of the disclosure. In some embodiments, the cell is a eukaryotic cell. In some embodiments, the eukaryotic cell is a mammalian cell. In some embodiments, the mammalian cell is selected from the group consisting of a CHO cell, a 293 cell, an NSO cell, a PER.C6 cell, and a B cell. In some embodiments, the mammalian cell is a 293-6E cell or a DG44 cell. In some embodiments, the cells express the antibodies or antigen binding fragments thereof of the disclosure. In some embodiments, the cell is a germline cell. 
     The disclosure provides cells producing the antibodies or antigen-binding fragments thereof of the disclosure 
     The disclosure provides a method of treating a disease in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of the antibodies or antigen-binding fragments thereof of the disclosure. 
     The disclosure provides a composition for use in treating a disease in a subject in need thereof, comprising a therapeutically effective amount of the antibodies or antigen-binding fragments thereof of the disclosure or the nucleic acids encoding the antibodies or antigen-binding fragments thereof of the disclosure. 
     The disclosure provides a composition for use in the manufacture of a medicament for the prevention or treatment of a disease in a subject in need thereof, comprising a therapeutically effective amount of the antibodies or antigen-binding fragments thereof of the disclosure or the nucleic acids encoding the antibodies or antigen-binding fragments thereof of the disclosure. 
     In some embodiments of the methods or compositions for use of the disclosure, the disease is rheumatoid arthritis. In some embodiments, the subject exhibits bone loss as a result of having rheumatoid arthritis. In some embodiments, administration of a therapeutically effective amount of the antibody or antigen-binding fragment thereof slows or reverses the bone loss in the subject. 
     In some embodiments of the methods or compositions for use of the disclosure, the disease is a cancer. In some embodiments, the cancer is selected from the group consisting of breast cancer, prostate cancer, endometrial cancer, uterine cancer, bladder cancer, kidney cancer, esophageal cancer, squamous cell carcinoma, uveal melanoma, glioma, glioblastoma, myeloma, pheochromocytoma, paraganglioma, follicular lymphoma, renal cell carcinoma, cendcal cancer, ovarian cancer, cervical cancer, lung cancer, colorectal cancer, brain cancer, pancreatic cancer, gastric cancer, intestinal cancer, testicular cancer, skin cancer, thyroid cancer, thymoma, head and neck cancer, liver cancer, pharynx cancer, adrenocortical cancer, cholangiocarcinoma, mesothelioma, sarcoma, leukemia, lymphoma, Hodgkin&#39;s disease, multiple myeloma, melanoma, astrocytoma, stomach cancer, and pulmonary adenocarcinoma. In some embodiments, a cell of the cancer expresses CLEC2D on the cell surface. In some embodiments, administration of a therapeutically effective amount of the antibodies or antigen-binding fragments thereof results in an anti-tumor response in the subject. 
     In some embodiments of the methods or compositions for use of the disclosure, the antibodies or antigen-binding fragments thereof are administered as a monotherapy. In some embodiments, the antibodies or antigen-binding fragments thereof are administered in combination with at least one of a T cell targeted immunomodulatory agent, a second immunomodulatory agent, a cancer vaccine, an adoptive cell therapy, an oncolytic virus, a second antibody therapy, a radiotherapy, an antibody drug conjugate, a small interfering RNA, a chemotherapy, an immunotherapy, an immune checkpoint inhibitor, a mitotic inhibitor, or a combination thereof. In some embodiments, the adoptive cell therapy comprises a CAR-T therapy. In some embodiments, administration of a therapeutically effective amount of the antibody or antigen-binding fragment thereof alleviates a sign or a symptom of the disease. 
     The disclosure provides an antibody library comprising at least about 108 unique monoclonal antibody clones, wherein at least about 80% of the antibody clones detectably and specifically bind a CLEC2D antigen. 
     In some embodiments of the antibody library of the disclosure, the CLEC2D antigen comprises an amino acid sequence selected from SEQ ID NOs: 886-920 and SEQ ID NOs: 930-1003. In some embodiments of the antibody library of the disclosure, the CLEC2D antigen comprises an amino acid sequence selected from SEQ ID NOs: 886-909 and SEQ ID NOs: 930-1003. In some embodiments, the CLEC2D antigen comprises a CLEC2D antigen expressed on a tumor cell surface, a variant of the CLEC2D antigen, or a homolog of the CLEC2D antigen. In some embodiments, the variant of the CLEC2D antigen comprises a fragment of the CLEC2D protein. In some embodiments, the homolog of the CLEC2D antigen comprises a human, a mouse, a dog, a rat or a cynomolgus CLEC2D. 
     The disclosure provides a method of modulating immunity in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of the antibodies or antigen-binding fragments of the disclosure or the nucleic acids encoding the antibodies or antigen-binding fragments thereof of the disclosure. 
     The disclosure provides a method of modulating (e.g., increasing) innate immunity in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of the antibodies or antigen-binding fragments of the disclosure or the nucleic acids encoding the antibodies or antigen-binding fragments thereof of the disclosure. 
     The disclosure provides a method of increasing the cytotoxicity of a natural killer cell in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of the antibodies or antigen-binding fragments thereof of the disclosure or the nucleic acids encoding the antibodies or antigen-binding fragments thereof of the disclosure. 
     The disclosure provides a method of modulating (e.g., increasing) adaptive immunity in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of the antibodies or antigen-binding fragments of the disclosure or the nucleic acids encoding the antibodies or antigen-binding fragments thereof of the disclosure. 
     The disclosure provides methods of screening a high diversity antibody gene library for antibodies that to a CLEC2D antibody comprising: (a) inserting a library of antibody genes into a phage protein gene and transforming a plurality of phages to produce a phage library, wherein the phages in the phage library display the library of antibody genes on the surface of the phage; (b) panning the phage library with a CLEC2D antigen for individual phages that bind to the CLEC2D antigen, thereby producing an enriched phage library that is enriched for antibody genes that encode antibodies that bind to the CLEC2D antigen; (c) repeating step (b) at least once or at least twice; (d) transferring the antibody genes from the enriched phage library to a yeast surface display library; (e) isolating individual yeast cells that bind to the CLEC2D antigen from the yeast surface display library; (f) culturing the isolated individual yeast cells that bind to the CLEC2D antigen to produce yeast surface display library clones; and (g) sequencing the yeast surface display library clones; thereby isolating antibody genes that bind to the CLEC2D antigen. 
     In some embodiments of the methods of screening of the disclosure, the panning step (b) comprises panning the phage library with CLEC2D coated magnetic beads. In some embodiments, the transferring step (d) comprises cloning the antibody genes into a yeast expression vector and transforming yeast cells. In some embodiments, the methods further comprise analyzing the surface expression of the antibody genes with a FLAG tag, a c-Myc tag, a polyhistidine tag or a V5 tag. In some embodiments, the testing step (e) comprises isolating yeast cells expressing antibody genes that bind to the CLEC2D antigen with flow cytometry. In some embodiments, the method further comprises repeating the flow cytometry isolation at least 1×, at least 2×, at least 3×, at least 4× or at least 5×. In some embodiments, the method further comprises cloning the antibody genes that bind to CLEC2D into a mammalian expression vector. 
     The disclosure provides methods of making a composition comprising anti-CLEC2D antibodies or antigen binding fragments thereof, comprising (a) transforming mammalian cells with a vector comprising a sequence encoding a promoter and a sequence encoding an anti-CLEC2D antibody or antibody fragment, wherein the sequence encoding the promoter and the anti-CLEC2D antibody or antibody fragment are operably linked; (b) culturing the mammalian cells under conditions suitable for the expression of the anti-CLEC2D antibody or antibody fragment; (c) centrifuging the cultured mammalian cells to produce a supernatant; (d) filtering the supernatant; and (e) purifying the filtered supernatant using liquid chromatography. 
     In some embodiments of the methods of the disclosure, the filtration step (d) comprises a 3 μm-30 μm filter. In some embodiments, the filtration step (d) further comprises a 0.22 μm filter. In some embodiments, the purifying step (e) comprises a Protein A column. In some embodiments, the protein A column is treated with a high salt wash buffer to remove host cell proteins. In some embodiments, the anti-CLEC2D antibody of fragment thereof is eluted using 30 mM Phosphate buffer at pH. 3.0-4.0. In some embodiments, the purifying step (e) further comprises an anion exchange chromatography (AEX) step. In some embodiments, the AEX step comprises a Q Sepharose column. In some embodiments, the Q Sepharose is pre-equilibrated in a pre-equilibration buffer comprising 10-100 mM Histidine. In some embodiments, the pre-equilibration buffer further comprises citrate, phosphate 2-(N-morpholino)ethanesulfonic acid (MES), acetate or a combination thereof. In some embodiments, the pre-equilibration buffer comprises a pH of 4.5-6.5. In some embodiments, the anti-CLEC2D antibody is eluted at step (e) with an elution buffer comprising 200-1000 mM NaC1, KCl or a combination thereof. In some embodiments, the elution buffer comprises a pH of 4.5-6.5. 
     In one aspect, this disclosure relates to the isolation of novel monoclonal antibodies that bind specifically to a CLEC2D antigen. The novel antibodies modulate (e.g., inhibit) the interaction of CD161 and CLEC2D to modify NK cell/immune cell mediated cytotoxicity and/or cytokine production. 
     In another aspect, this disclosure relates to cancer cells expressing CLEC2D are specifically recognized by these novel antibodies which may kill the tumor cells via ADCC (antibody dependent cellular cytotoxicity) and/or CDC (complement dependent cytotoxicity) and/or ADCP (antibody dependent cellular phagocytosis). 
     In a related aspect, this disclosure relates to methods of making an anti-CLEC2D antibody, comprising selecting from a high diversity antibody gene library an anti-CLEC2D antibody. In one embodiment, the high diversity antibody gene library is displayed through phage and/or yeast surface display. In one embodiment, the phage- and/or yeast-displayed high diversity antibody gene library is selected using purified CLEC2D antigen as a target. In one embodiment, the selected anti-CLEC2D antibody genes are expressed in a mammalian cell (e.g., Chinese hamster ovary (CHO) cell). In one embodiment, a single cell clone expressing an anti-CLEC2D antibody is expanded into a cell line and verified for anti-CLEC2D antibody expression. In one embodiment, overexpression of selected antibody clones is achieved through defined culture media, supplements, and specific bioreactor processes cumulatively described herein as upstream process development. In one embodiment, the anti-CLEC2D antibodies expressed from the cell line are purified to homogeneity, for example, through various filtration and chromatography, referred to herein as downstream purification processes. 
     The disclosure provides a method of treating a disease in a subject in need thereof, comprising: determining a level of CLEC2D protein in the subject; and administering a therapeutically effective amount of an anti-CLEC2D antibody to the subject. 
     In some embodiments of the methods of the disclosure, the disease is a cancer. In some embodiments, the cancer comprises breast cancer, prostate cancer, endometrial cancer, uterine cancer, bladder cancer, kidney cancer, esophageal cancer, squamous cell carcinoma, uveal melanoma, glioma, glioblastoma, myeloma, pheochromocytoma, paraganglioma, follicular lymphoma, renal cell carcinoma, cendcal cancer, ovarian cancer, cervical cancer, lung cancer, colorectal cancer, brain cancer, pancreatic cancer, gastric cancer, intestinal cancer, testicular cancer, skin cancer, thyroid cancer, thymoma, head and neck cancer, liver cancer, pharynx cancer, adrenocortical cancer, cholangiocarcinoma, mesothelioma, sarcoma, leukemia, lymphoma, Hodgkin&#39;s disease, multiple myeloma, melanoma, astrocytoma, stomach cancer, pulmonary adenocarcinoma, adenocarcinoma, acinic cell adenocarcinoma, adrenal cortical carcinomas, alveoli cell carcinoma, anaplastic carcinoma, basaloid carcinoma, basal cell carcinoma, bronchiolar carcinoma, bronchogenic carcinoma, renaladinol carcinoma, embryonal carcinoma, anometroid carcinoma, fibrolamolar liver cell carcinoma, follicular carcinomas, giant cell carcinomas, hepatocellular carcinoma, intraepidermal carcinoma, intraepithelial carcinoma, leptomanigio carcinoma, medullary carcinoma, melanotic carcinoma, menigual carcinoma, mesometonephric carcinoma, oat cell carcinoma, squamal cell carcinoma, sweat gland carcinoma, transitional cell carcinoma, tubular cell carcinoma, ameloblastic sarcoma, angiolithic sarcoma, botryoid sarcoma, endometrial stroma sarcoma, ewing sarcoma, fascicular sarcoma, giant cell sarcoma, granulositic sarcoma, immunoblastic sarcoma, juxaccordial osteogenic sarcoma, coppices sarcoma, leukocytic sarcoma (leukemia), lymphatic sarcoma (lympho sarcoma), medullary sarcoma, myeloid sarcoma (granulocitic sarcoma), austiogenci sarcoma, periosteal sarcoma, reticulum cell sarcoma (histiocytic lymphoma), round cell sarcoma, spindle cell sarcoma, synovial sarcoma, telangiectatic audiogenic sarcoma, Burkitt&#39;s lymphoma, NPDL, NML, NH, diffuse lymphomas, Hodgkin&#39;s lymphoma, non-Hodgkin&#39;s lymphoma, B-cell lymphoma, T-cell lymphoma, diffuse large B-cell lymphoma, acute myeloid lymphoma, chronic lymphocytic leukemia, chronic myeoloid leukemia, mantle cell lymphoma, and follicular lymphoma. In some embodiments, a cancer cell of the subject has an elevated level of CLEC2D protein when compared to a normal cell that does not have cancer. In some embodiments, an increased level of CLEC2D is associated with a poor prognostic outcome. 
     In some embodiments of the methods of the disclosure, the disease is an autoimmune or inflammatory disorder. In some embodiments, the autoimmune or inflammatory disorder is type I diabetes, rheumatoid arthritis, lupus, inflammatory bowel diseases, celiac disease, Crohn disease, ulcerative Colitis, psoriasis, or multiple Sclerosis. 
     In some embodiments of the methods of the disclosure, the disease is an autoimmune or inflammatory disorder. In some embodiments, the autoimmune disorder is type I diabetes, rheumatoid arthritis, lupus, inflammatory bowel diseases, celiac disease, Crohn disease, ulcerative Colitis, psoriasis, or multiple Sclerosis. 
     In some embodiments of the methods of the disclosure, the disease is infectious disease. In some embodiments, the disease is HIV infection, human Cytomegalovirus infection, Hepatitis B infection, Hepatitis C infection, Ebola virus infection, Dengue, Yellow fever, Listeriosis, Tuberculosis, Cholera, Malaria, Leishmaniasis, or Trypanosoma infection. 
     In another aspect, multiple in vitro and in vivo assays are used to characterize the novel antibodies produced from CHO cell lines which include, various biophysical parameters, antigen recognition, tumor cell surface binding, tumor cell death, production of cytokines, and analysis of downstream genes to define mode of action. These monoclonal antibodies are also tested for long term stability, various formulations relevant for therapeutic, prognostic and diagnostic uses in cancer, infectious diseases, autoimmune and chronic diseases. In another aspect, in vivo tumor suppression assays are carried out to establish anti-tumor activity of selected antibodies as monotherapy or in combination with other therapeutic products. 
     In one aspect, this disclosure further relates to the isolation of novel and unique monoclonal antibodies that bind specifically to CLEC2D antigen. In some aspect, the novel antibodies influence the interaction of CD161 and CLEC2D to modify immune cell (e.g., NK cell, B-cell, or T-cell) mediated cytotoxicity and/or cytokine production. In some aspects, various cancer cells, expressing CLEC2D, are recognized by these novel antibodies and have revealed cytotoxic effects through various means including, ADCC (antibody dependent cellular cytotoxicity) and/or CDC (Complement dependent cytotoxicity and/or ADCP (Antibody dependent cellular phagocytosis). In one aspect, the disclosure provides emphasis and postulates on the role of CLEC2D in cross-talk between lymphocytes and immune tolerance. In another aspect, in the realm of approved therapeutics or those in pre-clinical or clinical testing, the methods for identifying novel antibody molecules and related compositions provided herein comprise pharmaceutical features amenable to manufacturability/developability. 
     In one aspect, this disclosure relates to a method of treating a disease or disorder in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of the antibody or antigen-binding fragment thereof of, wherein the antibody is an anti-CLEC2D antibody selected from the group consisting of: A1, B1, E1, P1, U1, Y1, E2, I2 and L2, of Table 9A and B, as disclosed herein. 
     In one aspect, this disclosure relates to a method of modulating immunity in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of the antibody or antigen-binding fragment, wherein the antibody is an anti-CLEC2D antibody selected from the group consisting of: A1, B1, E1, P1, U1, Y1, E2, I2 and L2, of Table 9A and B, as disclosed herein. 
     In one aspect, this disclosure relates to a method of modulating (e.g., increasing) innate immunity in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of the antibody or antigen-binding fragment, wherein the antibody is an anti-CLEC2D antibody selected from the group consisting of: A1, B1, E1, P1, U1, Y1, E2, I2 and L2, of Table 9A and B, as disclosed herein. 
     In one aspect, this disclosure relates to a method of modulating (e.g., increasing) adaptive immunity in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of the antibody or antigen-binding fragment, wherein the antibody is an anti-CLEC2D antibody selected from the group consisting of: A1, B1, E1, P1, U1, Y1, E2, I2 and L2, of Table 9A and B, as disclosed herein. 
     In one aspect, this disclosure relates to a method of increasing the cytotoxicity of a natural killer cell in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of the antibody or antigen-binding fragment, wherein the antibody is an anti-CLEC2D antibody selected from the group consisting of: A1, B1, E1, P1, U1, Y1, E2, I2 and L2, of Table 9A and B, as disclosed herein. 
    
    
     
       BRIEF DESCRIPTION OF THE FIGURES 
       The features of the present disclosure will become fully apparent from the following description taken in conjunction with the accompanying figures. The patent or application file contains at least one drawing executed in color. Copies of this patent or patent application publication with color drawings will be provided by the Office upon request and payment of the necessary fee. With the understanding that the figures depict only several embodiments in accordance with the disclosure and are not to be considered limiting its scope, the disclosure will be described further through use of the accompanying figures. 
         FIGS. 1A-1C  illustrate present disclosure in a schematic format in:  FIG. 1A , scenario wherein CLEC2D and CD161 interacts resulting in tumor cells escaping immune cells;  FIG. 1B , scenario wherein interaction between CLEC2D and CD161 is blocked using an anti-CLEC2D antibody, resulting in lysis signal followed by killing of tumor cells; and  FIG. 1C , scenario wherein ligation of CLEC2D antigen with anti-CLEC2D antibody resulting in activation of NK cell and in elevation of cytokine expression followed by enhanced target cell clearance either by direct killing or by involving other immune cells 
         FIGS. 2  A- 2 F illustrate expression and purification of CLEC2D antigen in mammalian cell in:  FIG. 2A , generation of mammalian expression plasmids to express CLEC2D ecto-domain as soluble antigen. The construct was generated through gene synthesis followed by confirmation through restriction digestion and Sanger sequencing;  FIG. 2B , IMAC chromatography profile displaying purification of a soluble CLEC2D (Q72-V191), with inset showing elution profile of the CLEC2D antigen;  FIG. 2C , SDS-PAGE profile of load, wash and final eluted CLEC2D protein, demonstrating that the purified CLEC2D protein was homogenous and pure, and suitable for further downstream experimentation;  FIG. 2D , western blot of the purified CLEC2D protein, probed with a commercially available antibody against CLEC2D antigen;  FIG. 2E , ELISA assay showing the binding specificity of a commercial antibody against different concentrations of the purified CLEC2D antigen; and  FIG. 2F , SDS-PAGE analysis of the purified CLEC2D antigen incubated with PNGase enzyme under reducing conditions for 3 hrs or 6 hrs revealed deglycosylation of CLEC2D antigen. 
         FIG. 3  illustrates a schematic depiction of an antibody library screening strategy: the naïve antibody library screened against the target CLEC2D antigen using phage and yeast surface display systems. 
         FIGS. 4A-4E  illustrate phage panning of antibody library with CLEC2D antigen coated on magnetic beads in:  FIG. 4A , estimation of magnetic bead conjugation efficiency by flow cytometry;  FIG. 4B , restriction enzyme digestion of independent heavy chain clones after panning of Fab library;  FIG. 4C , restriction enzyme digestion of independent kappa light chain clones after panning of Fab library;  FIG. 4D , restriction enzyme digestion of independent heavy chain clones after panning of ScFv library; and  FIG. 4E , restriction enzyme digestion of independent kappa light chain clones after panning of ScFv library. 
         FIGS. 5A-5H  illustrate screening of antibody against CLEC2D using yeast surface display in:  FIG. 5A , plate images depicting yeast colony towards generation of ScFv antibody library through electroporation;  FIG. 5B , plate images depicting generation of haploid heavy and light chain antibody libraries;  FIG. 5C , plate images showing mating efficiency of haploid yeast strains containing heavy or light chain antibody libraries, wherein mating efficiency was estimated to be ˜29%;  FIG. 5D , representative flow cytometric analysis of binding of antibody molecules expressed on the yeast cell surface with CLEC2D antigen, the ScFv libraries were sorted multiple times to enrich high affinity yeast clones;  FIG. 5E , representative flow cytometric analysis of binding of antibody molecules expressed on the yeast cell surface with CLEC2D antigen, the Fab libraries were sorted multiple times to enrich high affinity yeast clones;  FIG. 5F , representative data on enrichment of yeast clones after multiple rounds of sorting, both in terms of expression and antigen recognition;  FIG. 5G , the individual yeast clones were separated and tested with CLEC2D antigen to identify yeast cell lines expressing high affinity antibody clones; and  FIG. 5H , representative flow cytometry data to show the percentage binding of a soluble CLEC2D antigen with monoclonal antibody clones. At least about 80% of the clones detectably and specifically bound to the CLEC2D antigen. 
         FIGS. 6A-6D  illustrate the peer group sequence analysis of clones screened through yeast display platform in:  FIG. 6A , bar graph showing the CDRH3 length distribution of selected molecules;  FIG. 6B , bar graph displaying relative amino acid frequency distribution for heavy chain CDRH3 (Kabat nomenclature);  FIG. 6C , pie chart exhibiting heavy chain consensus family distribution; and  FIG. 6D , pie chart exhibiting light chain consensus family distribution. 
         FIGS. 7A-7B  illustrate the mammalian expression constructs used to generate full-length monoclonal antibody in:  FIG. 7A , the vector designed to clone selected antibody variable heavy chain genes after screening through phage and yeast display platforms; and  FIG. 7B , the vector designed to clone selected antibody variable light chain (kappa) genes after screening through phage and yeast display platforms. Constructs were generated through gene synthesis followed by confirmation through restriction digestion and Sanger sequencing. 
         FIGS. 8A-8C  illustrate mammalian expression system to express full-length CLEC2D on the cell surface, as shown in:  FIG. 8A , CLEC2D gene expression construct was generated through gene synthesis followed by confirmation through restriction digestion and Sanger sequencing; and  FIG. 8B , flow cytometry with commercially available anti-CLEC2D antibody (4C7) showing expression of CLEC2D on transfected CHO cell surface (C4548); and  FIG. 8C , the surface expression of CLEC2D as monitored with anti-CLEC2D (4C7) antibody on fixed and non-permeabilized cells by confocal microscopy (60×). Binding of anti-CLEC2D antibody was observed on C4548 cells whereas no binding was observed in un-transfected CHO cells. The nucleus was counterstained with DAPI (blue). Scale bar is 10 μm. 
         FIGS. 9A-9C  illustrate anti-CLEC2D monoclonal antibody clones purified from transiently transfected CHO cell. Antibody was purified using protein A column chromatography, as shown in:  FIG. 9A , SDS-PAGE profile of representative Anti-CLEC2D antibodies. The purified antibodies were subjected to SDS-PAGE analysis in both non-reducing and reducing conditions. Anti-CLEC2D Antibody clone purified from C3566 was shown in lane 9, upper panel of reducing and non-reducing gels. All clones from lower panels, except clone in lane 4 revealed good profiles in reducing and non-reducing gels. Clones showing degraded products were not considered for further studies. Similar criteria was employed for other clones as described in example section;  FIG. 9B , the interaction of purified anti-CLEC2D antibody with CLEC2D antigen expressed on CHO cell surface through flow cytometry; Representative antibody clones, as exemplified by, C4577, C2907, C3566, C5582, C5397, were evaluated for CLEC2D binding on CHO cell lines either untransfected or transfected with full length CLEC2D construct. Shift in MFI towards right indicated binding of respective clones towards surface expressed CLEC2D antigen; and  FIG. 9C , representative images of interaction of anti-CLEC2D antibodies with CLEC2D antigen expressed on PC3 tumor cells. As shown in Table 22 a qualitative rating of binding was carried out, “+” indicating low binding to “+++” indicating very high binding. As exemplified, surface binding was not detected with antibody C4252, whereas with antibody C0610, low binding was observed thereby rated as (+) while other clones have showed differential yet significant surface binding. The nucleus was counterstained with DAPI (violet). Scale bar is 10 μm. 
         FIGS. 10A-10E  illustrate stable CHO cell line development expressing Anti-CLEC2D antibody, as shown in:  FIG. 10A , the binding studies carried out with surface expressed CLEC2D as monitored using supernatant obtained from CHO mini-pool samples transfected with Anti-CLEC2D antibody expression plasmid, using flow cytometry. Histogram represents extent of binding against surface CLEC2D antigen expressed on C4548 cell, as observed for various clones. Fold change in MFI has been plotted against individual mini-pools binding. Higher fold change indicating higher binding of anti-CLEC2D antibody to CLEC2D antigen;  FIG. 10B , single cell clone screening—Anti CLED2D antibody expressed from single cell clonal lines was purified and used for flow cytometry experiments. Higher fold change in fluorescence signal indicates stronger binding of anti-CLEC2D antibody binding to CLEC2D antigen;  FIG. 10C , flow cytometric analysis of monoclonal antibody producing stable CHO cell lines—anti-CLED2D antibody expressed from single cell clonal lines was purified and used for flow cytometry experiments. Multiple monoclonal cell lines expressing the Anti-CLEC2D antibodies were (such as C4608, C5093, C5511, C6481, C6726, C7720, C9103, C5848 and C3452) were tested for binding to CHO cell surface expressed CLEC2D antigen by flow cytometry. Fold increase in median fluorescence intensity was estimated and was observed to be in the range of 3-10 fold for multiple stable clones;  FIG. 10D , representative images of interaction of anti-CLED2D monoclonal antibodies produced from clonal CHO cell lines with the CLEC2D antigen expressed on PC3 tumor cell line. As depicted herein, various anti-CLEC2D antibodies showed differential yet significant surface binding to CLEC2D antigen on PC3 cell surface. The nucleus was counterstained with DAPI (violet). Scale bar is 10 μm; and  FIG. 10E , quantitative RT PCR performed on of anti-CLEC2D antibody-stable cell clones C4608 and C5511 to confirm stable integration of antibody heavy chain and light chain genes. GAPDH house-keeping gene was used as internal normalizer. The study was carried out for 60 generations of CHO monoclonal lines expressing the Anti-CLEC2D antibodies. 
         FIGS. 11A-11F  illustrate functional characterization of monoclonal anti-CLEC2D antibodies, as shown in:  FIG. 11A , the binding of anti-CLEC2D antibodies, C4608, C5511, C6481, C2438, C3452, C0949 on surface expressed CLEC2D on prostate cancer cell line, PC3. Shift in MFI towards right indicated binding of antibody to surface expressed CLEC2D antigen on PC3 cell line; and  FIG. 11B , representative flow cytometric analysis of cytotoxicity assay performed on PC3 target cells using PBMC as effector cells, at a ratio of 1:5 at a fixed concentration of 100 ug/mL of Anti-CLEC2D antibodies. Clones assessed for functionality herein were C5511, C4608 and C6481 with PBMC from Donor 1, while antibodies purified from clones C5392 and C3452 were tested with PBMC from Donor 2. The percentage of PC3 live cells is indicated by APC (eFluor 670) positive cells and dead cells indicates Sytox green-positive cells. Respective single cell clones have been labelled against each plot;  FIG. 11C , representative flow cytometry analysis of cytotoxicity assay performed on PC3 target cells using PBMC as effector cells (1:5), with increasing concentrations of anti-CLEC2D antibody (C5511) from 10 μg/mL to 200 ug/mL revealed increased dose dependent tumor cell cytotoxicity;  FIG. 11D , representative flow cytometric analysis of cytotoxicity assay performed on PC3 target cells using PBMC as effector cells at fixed concentration of anti-CLEC2D antibody C5511. The tumor to effector cell ratio (T:E) was increased from 1:5 to 1:10. The data revealed with increasing proportion of effector cells leads to higher levels of tumor cell cytotoxicity; and  FIG. 11E , end point cytotoxicity assay revealed significant cytotoxicity of tumor cells at 10 μg/mL. The assay also determines optimum concentration of anti-CLEC2D antibody to kill target cells using confocal microscopy. Upper panel indicates all control treatments where no cytotoxicity was observed as expected, and lower panel indicates the enhanced PC3 tumour cell death when treated with increasing the concentration of anti-CLEC2D antibody (C6726) in presence of PBMC (T:E=1:5). The maximum cell death were observed at concentration of 50 ug/ml of Anti-CLEC2D antibody. PC3 tumor cells—Green; PBMC—red; Dead cells—Blue; and  FIG. 11F , end point cytotoxicity assay using selected anti-CLEC2D antibody to kill target cells using confocal microscopy. No cytotoxicity observed in control treatments like PC3 tumor cell alone, PBMC alone, PBMC with isotype human IgG1 antibody. PC3 tumor cell cytotoxicity was observed when Anti-CLEC2D antibody (C6726, C5848, C4608, C5511 and C6481) clones were used. Size enhanced images revealed PC3 tumor cells were surrounded by effector cells inducing tumor cell death. PC3 tumor cells—Green; PBMC—red; Dead cells—Blue. 
         FIGS. 12A-12D  illustrate NK cell mediated cytotoxicity of tumor cells with anti-CLEC2D antibody, a shown in:  FIG. 12A , cytotoxicity of PC3 tumor cells when treated with purified NK cells and anti-CLEC2D antibodies (C6481 &amp; C5511) at 100 ug/ml. The data revealed 86% NK cell mediated cytotoxicity of PC3 tumor cells at T:E of 1:1. The percentage of PC3 dead cells indicates Sytox green-positive cells;  FIG. 12B , no target cell death was observed when incubated with either isotype control (human IgG1 antibody) or with only NK cells increasing T:E ratio starting from 1:0.5 to 1:10; Scale bar is 10 μm and  FIG. 12C , anti-CLEC2D antibody alone cannot induce cytotoxicity of PC3 tumor cell; Scale bar is 10 μm and  FIG. 12D  anti-CLEC2D antibody C5511 (at 50 ug/mL) revealed increasing PC3 tumor cell death with increasing T:E ratio starting from 1:0.5, 1:5 and 1:10 C5511. Scale bar is 10 μm. 
         FIG. 13  illustrates cytotoxicity of PC3 tumor cells treated with isolated T cells and anti-CLEC2D antibodies (C5511 &amp; C6481) at 100 ug/ml. The percentage of dead PC3 tumor cells indicated by Sytox green-positive cells. 
         FIGS. 14A-14B  illustrate live cell imaging with Anti-CLEC2D antibody dependent cytotoxicity of PC3 tumor cells, a shown in:  FIG. 14A , live cell imaging revealed cytotoxicity of PC3 tumor cells over a period of incubation with human PBMC cells and Anti-CLEC2D antibody at 200 μg/ml. The assay was carried out for 20 hrs in a humidifier maintained at 37° C. and 5% CO2 during the image acquisition. On the contrary, incubation with Control human IgG1 antibody (200 μg/ml) did not cause tumor cell cytotoxicity. Live PC3 tumor cells—Green; PBMC—Red; Dead cells—Blue; Scale bar is 20 μm and  FIG. 14B , live cell imaging revealed cytotoxicity of PC3 tumor cells over a period of incubation with human NK cells and Anti-CLEC2D antibody at 200 μg/ml. The assay was carried out for 20 hrs in a humidifier maintained at 37° C. and 5% CO2 during the image acquisition. On the contrary, incubation with Control human IgG1 antibody (200 μg/ml) did not cause tumor cell cytotoxicity. Live PC3 tumor cells—Green; NK cells—Red; Dead cells—Blue. Scale bar is 20 μm. 
         FIGS. 15A-15G  illustrate predictive models of anti-CLEC2D antibodies, as shown in:  FIG. 15A , cartoon representation of epitope recognition (Chain A—Dark Blue, Chain B—Cyan) &amp; CD161 (Chain C—Orange red, Chain D—Purple) complex PDB ID 5MGT;  FIG. 15B , the red selections denote residues within 6 Å of NKR-P1&#39;s chains;  FIG. 15C , ribbon representation of refined anti-CLEC2D antibody structures; respective clones for specific anti-CLEC2D monoclonal antibodies have been labelled appropriately. Variable light chain is depicted in darker shade while heavy chain variable region is shown in white;  FIG. 15D , represents selected conformations following PIZSA scoring and conformation clustering principle, belonging to C4608, contributed to one of the clusters interacting against CLEC2D (darker shade);  FIG. 15E , a visualization of the residues selected for mutation to determine if the G00001-G00004-G00007-G00010-G00015 cluster combination from C4608 contains the binding site towards CLEC2D antigen;  FIG. 15F , represents selected conformations following PIZSA scoring and conformation clustering principle, belonging to C5511, contributed to one of the clusters interacting against CLEC2D (darker shade); and  FIG. 15G , a visualization of the residues selected for mutation to determine if the G00001-G00005-G00011-G00019-G00020 cluster combination from C5511 contains the binding site towards CLEC2D antigen. 
         FIGS. 16A-16G  illustrate on identified epitope patch on CLEC2D antigen against anti-CLEC2D antibody clones C4608 and C5511;  FIG. 16A , surface representation of anti-CLEC2D antibody C4608 contact points on CLEC2D antigen;  FIG. 16B , anti-CLEC2D antibody C4608 contact points on CLEC2D antigen that are overlapping with CD161 binding regions on CLEC2D;  FIG. 16C , surface representation of anti-CLEC2D antibody C5511 contact points on CLEC2D antigen;  FIG. 16D , anti-CLEC2D antibody C5511 contact points with CLEC2D antigen that are overlapping with CD161 binding regions on CLEC2D; In all depictions darker shade indicates the interacting residue locations on CLEC2D antigen;  FIG. 16E , anti-CLEC2D antibody mediated disruption of CLEC2D and CD161 interaction-monitoring of CLEC2D antigen bead conjugation efficiency check;  FIG. 16F , binding of CD161-FC to CLEC2D antigen was observed on magnetic beads in concentration depend manner;  FIG. 16G , flow cytometric monitoring of CD161 binding in the absence and presence of Anti-CLEC2D antibody as compared with control, as a measure of disruption of CD161 and CLEC2D binding, as indicated by the solid black arrow. 
         FIGS. 17A-17B  illustrate NK cell activation with anti-CLEC2D antibody, as shown in:  FIG. 17A , anti-CLE2D antibody C5511 induces CD69 expression indicating NK cell activation towards becoming cytotoxic. Respective experimental conditions have been mentioned against each plot. IL2 treatment was carried out as positive control of CD69 overexpression; and  FIG. 17B , anti-CLEC2D antibody mediated CD69 expression is higher compared to PC3 cell primed CD69 expression level on NK cells. 
         FIGS. 18A-18D  illustrate effects of anti-CLEC2D antibody C5511 on cytokine expression by effector cells, as shown in:  FIG. 18A , anti-CLEC2D antibody C5511 was used at concentrations of 10 μg/mL and 100 μg/mL to monitor elevation in IFNγ expression level;  FIG. 18B , anti-CLEC2D antibody C5511 was used at concentration of 100 ug/mL in the presence or absence of PC3 cells (E:T=10:1). IFNγ expression was monitored in the CD3+ve gated population;  FIG. 18C , anti-CLEC2D antibody C5511 was used at concentration of 100 ug/mL in the presence or absence of PC3 cells (E:T=10:1). IFNγ expression was monitored in the CD3-ve gated population; and  FIG. 18D , anti-CLEC2D antibody C5511 was used as at concentrations of 100 μg/mL in the presence or absence of isolated NK cell. IFNγ overexpression was observed with anti-CLEC2D antibody C5511. 
         FIGS. 19A-19G  illustrate mammalian expression constructs used to generate full-length monoclonal antibody. Constructs were generated through gene synthesis followed by confirmation through restriction digestion and Sanger sequencing, as shown in:  FIG. 19A , vector designed to clone selected antibody variable heavy chain genes in IgG4 backbone;  FIG. 19B , vector designed to clone selected antibody variable heavy chain genes in IgG1 N to A backbone;  FIG. 19C , flow cytometric analysis of binding of Anti-CLEC2D antibody with IgG4 isotype backbone (C3256 and C3276) to CLEC2D antigen expressed on surface of CHO cells. Binding was compared with un-transfected CHO cells, as estimated from peak shift towards right; FIG.  19 D, cytotoxicity of Anti-CLEC2D antibody using various antibody isotypes. IgG1 isotype (C3452 &amp; C4608) and IgG4 isotype (C3256 &amp; C3276) Anti-CLEC2D antibodies exhibited significant cytotoxicity when incubated with freshly isolated PBMC and PC3 tumor cells;  FIG. 19E , anti-CLEC2D antibody produced as afucosylated monoclonal antibodies C0613, C1301, C6268, C1699, C2437, C9832, C8900 and C7749 revealed binding to CHO cell surface expressed CLEC2D antigen by flow cytometry;  FIG. 19F , NK cell-mediated cytotoxicity of PC3 tumor cells with the afucosylated anti-CLEC2D antibody (C7749, C8800,C9832) used at  5 X lesser concentration than C5511. The data revealed afucosylated Anti-CLEC2D antibodies achieved nearly equal cell death at 5 times less concentration, indicating afucosylated Anti-CLEC2D antibodies are more cytotoxic; and  FIG. 19G , CDC mediated cytotoxicity was measured for anti-CLEC2D antibody C5511 using Ramos and PC3 tumor cell lines. Rituximab was used as positive control. 
         FIGS. 20A-20K  illustrate anti-tumor effects in cancer xenograft mouse model. HuNOG-EXL mice were used for PC3 xenograft and the tumor bearing animals were randomized and used for injecting Anti-CLEC2D antibody product, as shown in:  FIG. 20A , tumor volume vs. time plot demonstrating significant anti tumor effects observed with Anti-CLEC2D antibody alone or in combination with anti-PDL1 antibody;  FIG. 20B , images displaying immune cell infiltration through staining of CD3+ T cells in the tumor micro environment;  FIG. 20C , images of mice with the xenograft showing Alexa 647 labelled anti-CLEC2D antibody injected into the tumor over a 96-hour period;  FIG. 20D , effect of test compounds on tumor volume in humanized (huNOG-EXL) mice bearing subcutaneous PC-3 tumor xenografts (up to day 36). Each treatment group consisted of 5 animals and named as C5511 mAb group, Vehicle control IgG1 group and C6481 mAb group. Values are expressed as mean of 2-5 animals in each group. Statistical analysis was carried out by Two-way ANOVA followed by Bonferroni post-tests using Graph Pad Prism (Version 8.3.0). ** p&lt;0.01 statistically significant (Day 36) when C5511 mAb group was compared with Vehicle control IgG1 group;  FIG. 20E , effect of test compounds on tumor volume in humanized (huNOG-EXL) mice bearing subcutaneous PC-3 tumor xenografts (up to day 24). Each treatment group consisted of 5 animals and named as C5511 mAb group, Vehicle control IgG1 group and C6481 mAb group. Values are expressed as mean of 2-5 animals in each group. Statistical analysis was carried out by Two-way ANOVA followed by Bonferroni post-tests using Graph Pad Prism (Version 8.3.0). *** p&lt;0.001 and * p&lt;0.05 statistically significant (Day 24) when C5511 mAb group and C6481 mAb group, respectively were compared to Vehicle control IgG1 group;  FIG. 20F , effect of test compounds on delta tumor volume in humanized (huNOG-EXL) mice bearing subcutaneous PC-3 tumor xenografts (up to day 36). Each treatment group consisted of 5 animals and named as C5511 mAb group, Vehicle control IgG1 group and C6481 mAb group. Values are expressed as mean of 2-5 animals in each group. Statistical analysis was carried out by Two-way ANOVA followed by Bonferroni post-tests using Graph Pad Prism (Version 8.3.0). ** p&lt;0.01 statistically significant (Day 36) when C5511 mAb group was compared to Vehicle control IgG1 group;  FIG. 20G , effect of test compounds on delta tumor volume in humanized (huNOG-EXL) mice bearing subcutaneous PC-3 tumor xenografts (up to day 24). Each treatment group consisted of 5 animals and named as C5511 mAb group, Vehicle control IgG1 group and C6481 mAb group. Values are expressed as mean of 2-5 animals in each group. Statistical analysis was carried out by Two-way ANOVA followed by Bonferroni post-tests using Graph Pad Prism (Version.8.3.0). *** p&lt;0.001 and * p&lt;0.05 statistically significant (Day 24) when C5511 mAb group and C6481 mAb group, respectively were compared to Vehicle control IgG1 group;  FIG. 20H , effect of test compounds on relative tumor volume in humanized (huNOG-EXL) mice bearing subcutaneous PC-3 tumor xenografts (up to day 36). Each treatment group consisted of 5 animals and named as C5511 mAb group, Vehicle control IgG1 group and C6481 mAb group. Values are expressed as mean of 2-5 animals in each group. Statistical analysis was carried out by Two-way ANOVA followed by Bonferroni post-tests using Graph Pad Prism (Version 8.3.0). * p&lt;0.05 statistically significant (Day 36) when C5511 mAb group was compared to Vehicle control IgG1 group;  FIG. 20I , effect of test compounds on relative tumor volume in humanized (huNOG-EXL) mice bearing subcutaneous PC-3 tumor xenografts (up to day 24). Each treatment group consisted of 5 animals and named as C5511 mAb group, Vehicle control IgG1 group and C6481 mAb group. Values are expressed as mean of 2-5 animals in each group. Statistical analysis was carried out by Two-way ANOVA followed by Bonferroni post-tests using Graph Pad Prism (Version.8.3.0). *** p&lt;0.001 and * p&lt;0.05 statistically significant (Day 24) when C5511 mAb group and C6481 mAb group, respectively were compared to Vehicle control IgG1 group;  FIG. 20J , effect of test compounds on delta relative tumor volume in humanized (huNOG-EXL) mice bearing subcutaneous PC-3 tumor xenografts (up to day 36). Each treatment group consisted of 5 animals and named as C5511 mAb group, Vehicle control IgG1 group and C6481 mAb group. Values are expressed as mean of 2-5 animals in each group. Statistical analysis was carried out by Two-way ANOVA followed by Bonferroni post-tests using Graph Pad Prism (Version.8.3.0). * p&lt;0.05; and statistically significant (Day 36) when C5511 mAb group was compared to Vehicle control IgG1 group; and  FIG. 20K , effect of test compounds on delta relative tumor volume in humanized (huNOG-EXL) mice bearing subcutaneous PC-3 tumor xenografts (up to day 24). Each treatment group consisted of 5 animals and named as C5511 mAb group, Vehicle control IgG1 group and C6481 mAb group. Values are expressed as mean of 2-5 animals in each group. Statistical analysis was carried out by Two-way ANOVA followed by Bonferroni post-tests using Graph Pad Prism (Version.8.3.0). *** p&lt;0.001 and * p&lt;0.05 statistically significant (Day 24) when C5511 mAb group and C6481 mAb group, respectively were compared to Vehicle control IgG1 group. 
         FIGS. 21A-21I  illustrate characterization of purified Anti-CLEC2D antibody product, as shown in:  FIG. 21A , SDS-PAGE analysis of purified C5511 antibody in non reducing and reducing conditions;  FIG. 21B , TIC chromatogram from Intact Mass spectrometry analysis of Anti-CLEC2D antibody (3 replicates);  FIG. 21C , WCX chromatogram analysis of Anti-CLEC2D antibody;  FIG. 21D , Size Exclusion chromatogram of Anti-CLEC2D antibody;  FIG. 21E , ELISA assay development of Anti-CLEC2D antibody against CLEC2D purified biotinylated antigen. The data was fit to one site binding model to calculate Kd of Anti-CLEC2D antibody;  FIGS. 21E and 21F , CLEC2D antigen affinity based binding studies of representative Anti-CLEC2D antibody. FIG. G, Purified CLEC2D antigen ecto-domain was used as source of antigen in BIACORE studies; Response monitored has been plotted against time;  FIG. 21H , affinity based binding studies of representative Anti-CLEC2D antibody molecules with FcRn at pH 5.9; and  FIG. 21I , affinity based binding studies of representative Anti-CLEC2D antibody molecules with FcRn at at pH 7.4. 
         FIGS. 22A-22C  illustrate that anti-CLEC2D antibody for plausible diagnostic and prognostic applications, as shown in:  FIG. 22A , selection of Anti-CLEC2D antibody (C0949) based on binding characteristics. Four Anti-CLEC2D antibodies were evaluated (C2779, C2438, C0949 and C2543) for CLEC2D binding on PC3 target cells. C0949 showed excellent binding and peak median shift;  FIG. 22B , anti-CLEC2D antibody C0949 recognizes CLEC2D antigen on multiple prostate cancer cell lines; and  FIG. 22C , anti-CLEC2D antibody C0949 recognizes CLEC2D antigen on multiple tumor cell lines. Specific binding and fold change in mean fluorescence was calculated by ratio of mean FITC fluorescence between test and control. 
         FIGS. 23A-23D  illustrate that anti-CLEC2D antibody recognize CLEC2D antigen on prostate cancer tumor cells, as shown in:  FIG. 23A , expression level of CLEC2D antigen on prostate cancer disease stage after TCGA data analysis;  FIG. 23B , expression level of CLEC2D antigen on prostate cancer cell lines PC3, DU145, 22RV1 and LnCap;  FIG. 23C , expression level of CLEC2D antigen on prostate cancer cell lines PC3, LnCap, 22RV1, and DU145 with induction using LPS, Poly I:C, IFN-γ, PBMC supernatant, PBMC cells, NK cells and T cells. Upper panel with anti-CLEC2D antibody, lower panel representing the merged image; and  FIG. 23D , human tissue microarray slides stained with anti-CLEC2D antibody C2685 showing staining of tumor cells in malignant prostate cancer tissue. 
         FIGS. 24A-24D  illustrate that anti-CLEC2D antibody recognize CLEC2D antigen on various other tumor cells, as shown in:  FIG. 24A , TCGA data analysis for CLEC2D antigen expression in various cancers;  FIG. 24B , expression level of CLEC2D antigen on various tumor cell lines HepG2 (liver cancer), LN229 (Glioblastoma), SKOV3 (Ovary cancer), BT474 (Breast cancer), NCI-H929 (Myeloma), and Ramos (Lymphoma);  FIG. 24C , expression level of CLEC2D antigen on BT474 (Breast cancer), SKOV3 (Ovary cancer), LN229 (Glioblastoma), Ramos (Lymphoma), NCI-H929 (Myeloma) and HepG2 (liver cancer), upon induction with LPS, Poly I:C, IFNγ;  FIG. 24D , anti-CLEC2D antibody C5511 mediated cytotoxicity observed on SKOV3 (ovary cancer) at 100 μg/ml; and anti-CLEC2D antibodies C5511 and C6481 mediated cytotoxicity observed on HepG2 (liver cancer) cell lines at 100 m/ml. The percentage of dead cells indicated by Sytox green-positive cells. 
         FIGS. 25A-25E  illustrate lymphocyte proliferation assay with anti-CLEC2D antibody using flow cytometry analysis, as shown in:  FIG. 25A , Antibody wet-coating protocol;  FIG. 25B , Air dried antibody coating protocol;  FIG. 25C , High density pre-culture protocol;  FIG. 25D , measurement of IFNγ cytokine secretion from effector cells when PBMC are incubated with Anti-CLEC2D antibodies (C5511, C4608, C6481) for extended period. Treatment with OKT3 antibody was used as a positive control; and  FIG. 25E , measurement of IL2 cytokine secretion from effector cells when PBMC are incubated with Anti-CLEC2D antibodies (C5511, C4608, C6481) for extended period. Treatment with OKT3 antibody was used as a positive control. PBMCs were treated with anti CD3 antibody OKT3 (1 μg/ml), Anti-CLEC2D antibody C4608, C5511 and C6481 (1 μg/ml, 10 μg/ml, 50 μg/ml &amp; 100 μg/ml) and incubated for four days. The fluorescent proliferation dye status was monitored using flow cytometer. Untreated PBMC was used as a control. 
         FIG. 26  illustrates histogram overlay showing binding of anti-CLEC2D antibodies (C3566 and C5511) against CLEC2D antigen homologs from Rat, Mouse and cynomolgus monkey, expressed on CHO cell surface, using flow cytometric analysis. 
     
    
    
     DETAILED DESCRIPTION 
     Modulation of immune cell checkpoint receptors via antibody-based/directed therapeutic approaches has been gaining constant interests over the past few years. The largest efforts have been centered on T cell checkpoint modulation. However, there is an increasing attention in B cell, NK cell, and myeloid cell checkpoint modulation as well. The innate immune system includes natural killer (NK) cells, which possess the ability to recognize and induce the cytotoxicity of a wide range of target cells, such as, tumor cells or virus infected cells. NK cells do not need any prior antigen sensitization. Apart from direct cytotoxicity, NK cells also participate in the initiation and progress of the adaptive immune response through the production and secretion of cytokines. Usually, these responses are regulated by adequate balance of signals induced by the interaction of a wide array of surface-activating and surface-inhibitory receptors with ligands on the surface of target cells. Modulation of NK cell numbers and/or its relevant function through a variety of agents such as monoclonal antibodies, cytokines may result in enhanced anti-tumor activity. These agents can be offered either alone or in combination as potential therapeutics. Therefore, anti-cancer activity of NK cell can be unleashed through harnessing surface receptors, both activating and/or inhibitory kinds. 
     Blocking these interactions may be a new therapeutic option for treatment of several cancers. However, the finding, understanding and designs need to be tuned and therapeutic treatment needs to be further tailored for specific receptor as targets against various cancers, which is still unmet. 
     Unless otherwise defined herein, scientific and technical terms used in connection with the present disclosure shall have the meanings that are commonly understood by those of ordinary skill in the art. Further, unless otherwise required by context, singular terms shall include the plural and plural terms shall include the singular as is considered appropriate to the context and/or application. The various singular/plural permutations may be expressly set forth herein for the sake of clarity. Generally, nomenclatures used in connection with, and techniques of biotechnology, immunology, molecular and cellular biology, recombinant DNA technology described herein are those well known and commonly used in the art. Certain references and other documents cited herein are expressly incorporated herein by reference. In case of conflict, the present specification, including definitions, will control. The materials, methods, figures and examples are illustrative only and not intended to be limiting. 
     Furthermore, the methods, preparation and use of the antibody naïve library disclosed employ, unless otherwise indicated, conventional techniques in molecular biology, biochemistry, computational chemistry, cell culture, recombinant DNA technology, Polymerase Chain Reaction (PCR) and related fields. These techniques, their principles, and requirements are explained in the literature and known to a person skilled in the art. 
     Before the method of generating the antibody naïve library and the nucleic acids which encode the antibody naïve library and other embodiments of the present disclosure are disclosed and described, it is to be understood that the terminologies used herein are for the purpose of describing particular embodiments only and are not intended to be limiting. It must be noted that, as used in the specification and the appended claims, the singular forms “a,” “an” and “the” include plural referents unless the context clearly dictates otherwise. 
     In one embodiment, the terms “library” and “libraries” are used interchangeably within this disclosure, which relate to the product of the disclosure. In one embodiment, it refers to a collection or pool of nucleic acid sequences. In one embodiment, it refers to a collection or pool of amino acid sequences. In some embodiments, it refers to a collection or pool of organisms that comprise a collection or pool of amino acid sequences or nucleic acid sequences. In some embodiments, the organisms are bacteriophages (phages) or yeast (e.g.,  Saccharomyces cerevisiae ). 
     In one embodiment, the terms ‘pooling’, ‘pooled’, ‘pool’, and ‘pools’ in the context of the instant disclosure means combining the samples/nucleic acid sequences/nucleic acid fragments/gene clones/amplified product/antibodies obtained by employing the method of the instant disclosure from multiple donors i.e., more than one donor. 
     In one embodiment, the term “PBMC” refers to any peripheral blood cell having a round nucleus consisting of lymphocytes (T cells, B cells, NK cells) and monocytes, erythrocytes, platelet, and granulocytes (neutrophils, basophils, and eosinophils). 
     Antigens 
     As used herein, the terms “antigen” or “immunogen” refer to any foreign substance which induces an immune response in the body. In one embodiment, an antigen is a cellular protein. In one embodiment, an antigen is a cell surface protein. 
     The antigen may be isolated or derived from any species. Representative species include, but are not limited to  Homo sapiens, Mus musculus, Rattus norvegicus, Canis lupis familiaris  and  Cynomolgus Macaca fascicularis . In some embodiments, the antigen is a fragment of a wild type protein isolated or derived from  Homo sapiens, Mus musculus, Rattus norvegicus, Canis lupis familiaris  or  Cynomolgus Macaca fascicularis . In some embodiments, the antigen is a mutant variant of a protein from  Homo sapiens, Mus musculus, Rattus norvegicus, Canis lupis familiaris  or  Cynomolgus Macaca fascicularis . In some embodiments, antigens can be mutated to increase the solubility and/or stability of the antigen. For example, a CLEC2D antigens can include a mutation at H176C to introduce an additional disulphide bridge with the Cys163 amino acid to increase the stability and homogeneity of the expressed protein. 
     In some embodiments, the antigen includes an epitope tag at either the N or C terminus of the polypeptide. Exemplary tags include, but are not limited to polyHistidine tags and FLAG tags. Any epitope tag known in the art is envisaged as within the scope of the disclosure. 
     C-type lectin domain family 2 member D (CLEC2D), also referred to as CLAX, Lectin Like Transcript-1 (LLT1) and OCIL, is a member of the natural killer cell receptor C-type lectin family. CLEC2D binds to Killer Cell Lectin Like Receptor B1 (KLRB1). KLRB1 is also known as CD161, CLEC5B, NKR, NKR-P1, NKR-P1A, NKRP1A and hNKR-P1A. All orthologs and isoforms of CLEC2D and CD161 are considered to be within the scope of the present disclosure. 
     In some embodiments, a C-type lectin domain family 2 member D (CLEC2D) protein or any of its aliases or homologs, known in the art, whether from humans or other species, represents a target antigen of an antibody produced by the methods described herein. 
     In some embodiments, the antigen is a CLEC2D antigen that has at least 85%, at least 90%, at least 95%, at least 96%, at least 97% at least 98%, at least 99% or 100% identity to a CLEC2D sequence isolated or derived from  Homo sapiens, Mus musculus, Rattus norvegicus, Canis lupis familiaris  and  Cynomolgus Macaca fascicularis.    
     In some embodiments, a CD161 protein or any of its aliases or homologs, known in the art, whether from humans or other species, represents a target antigen of an antibody produced by the methods described herein. 
     In some embodiments, the CD161 antigen has at least 85%, at least 90%, at least 95%, at least 96%, at least 97% at least 98%, at least 99% or 100% identity to a CD161 sequence isolated or derived from  Homo sapiens, Mus musculus, Rattus norvegicus, Canis lupis familiaris  and  Cynomolgus Macaca fascicularis.    
     Exemplary antigens are shown in Table 1 below. 
     
       
         
           
               
             
               
                 TABLE 1 
               
             
            
               
                   
               
               
                 Representative CLEC2D and CD161 Polypeptide Sequences 
               
            
           
           
               
               
               
            
               
                 SEQ ID 
                 Description 
                 Amino Acid Sequence 
               
               
                   
               
               
                 SEQ ID 
                 Human ( Homo   
                 MHDSNNVEKDITPSELPANPGCLHSKEHSIKATLIWRLFFLIMFLTIIVCGMVAALSAIRANCHQ 
               
               
                 886 
                   sapiens ) 
                 EPSVCLQAACPESWIGFQRKCFYFSDDTKNWTSSQRFCDSQDADLAQVESFQELNFLLRYKGP 
               
               
                   
                 CLEC2D 
                 SDHWIGLSREQGQPWKWINGTEWTRQFPILGAGECAYLNDKGASSARHYTERKWICSKSDI 
               
               
                   
                 construct 1 
                 HV 
               
               
                   
               
               
                 SEQ ID 
                 Human ( Homo   
                 QAACPESWIGFQRKCFYFSDDTKNWTSSQRFCDSQDADLAQVESFQELNFLLRYKGPSDHWI 
               
               
                 887 
                   sapiens ) 
                 GLSREQGQPWKWINGTEWTRQFPILGAGECAYLNDKGASSARHYTERKWICSKSDIHVHHH 
               
               
                   
                 CLEC2D 
                 HHHHH 
               
               
                   
                 construct 2 
                   
               
               
                   
               
               
                 SEQ ID 
                 Human ( Homo   
                 QAACPESWIGFQRKCFYFSDDTKNWTSSQRFCDSQDADLAQVESFQELNFLLRYKGPSDHWI 
               
               
                 888 
                   sapiens ) 
                 GLSREQGQPWKWINGTEWTRQFPILGAGECAYLNDKGASSARCYTERKWICSKSDIHVHHH 
               
               
                   
                 CLEC2D 
                 HHHHHG 
               
               
                   
                 construct 3 
                   
               
               
                   
               
               
                 SEQ ID 
                 Human ( Homo   
                 MSFVSLLLVGILFHATQAQAACPESWIGFQRKCFYFSDDTKNWTSSQRFCDSQDADLAQVES 
               
               
                 889 
                   sapiens ) 
                 FQELNFLLRYKGPSDHWIGLSREQGQPWKWINGTEWTRQFPILGAGECAYLNDKGASSARH 
               
               
                   
                 CLEC2D 
                 YTERKWICSKSDIHVHHHHHHHH 
               
               
                   
                 construct 4 
                   
               
               
                   
               
               
                 SEQ ID 
                 Human ( Homo   
                 MMSFVSLLLVGILFHATQAQAACPESWIGFQRKCFYFSDDTKNWTSSQRFCDSQDADLAQV 
               
               
                 890 
                   sapiens ) 
                 ESFQELNFLLRYKGPSDHWIGLSREQGQPWKWINGTEWTRQFPILGAGECAYLNDKGASSAR 
               
               
                   
                 CLEC2D 
                 CYTERKWICSKSDIHVHHHHHHHHG 
               
               
                   
                 construct 5 
                   
               
               
                   
               
               
                 SEQ ID 
                 Human ( Homo   
                 MMSFVSLLLVGILFHATQAHHHHHHHHDDDDKQAACPESWIGFQRKCFYFSDDTKNWTSS 
               
               
                 891 
                   sapiens ) 
                 QRFCDSQDADLAQVESFQELNFLLRYKGPSDHWIGLSREQGQPWKWINGTEWTRQFPILGA 
               
               
                   
                 CLEC2D 
                 GECAYLNDKGASSARCYTERKWICSKSDIHV 
               
               
                   
                 construct 6 
                   
               
               
                   
               
               
                 SEQ ID 
                 Human ( Homo   
                 HHHHHHHHDDDDKQAACPESWIGFQRKCFYFSDDTKNWTSSQRFCDSQDADLAQVESFQE 
               
               
                 892 
                   sapiens ) 
                 LNFLLRYKGPSDHWIGLSREQGQPWKWINGTEWTRQFPILGAGECAYLNDKGASSARCYTER 
               
               
                   
                 CLEC2D 
                 KWICSKSDIHV 
               
               
                   
                 construct 7 
                   
               
               
                   
               
               
                 SEQ ID 
                 Human ( Homo   
                 MMSFVSLLLVGILFHATQAQAACPESWIGFQRKCFYFSDDTKNWTSSQRFCDSQDADLAQV 
               
               
                 893 
                   sapiens ) 
                 ESFQELNFLLRYKGPSDHWIGLSREQGQPWKWINGTEWTRQFPILGAGECAYLNDKGASSAA 
               
               
                   
                 CLEC2D 
                 CAAAAAWICSKSDIHVHHHHHHHH 
               
               
                   
                 construct 8 
                   
               
               
                   
               
               
                 SEQ ID 
                 Human ( Homo   
                 MQLLRCFSIFSVIASVLAQAACPESWIGFQRKCFYFSDDTKNWTSSQRFCDSQDADLAQVESF 
               
               
                 894 
                   sapiens ) 
                 QELNFLLRYKGPSDHWIGLSREQGQPWKWINGTEWTRQFPILGAGECAYLNDKGASSAACA 
               
               
                   
                 CLEC2D 
                 AAAAWICSKSDIHVEFEQKLISEEDLDYKDDDDKENLYFQGLQASGGGGSGGGGSGGGGSQE 
               
               
                   
                 construct 9 
                 LTTICEQIPSPTLESTPYSLSTTTILANGKAMQGVFEYYKSVTFVSNCGSHPSTTSKGSPINTQYV 
               
               
                   
                   
                 F 
               
               
                   
               
               
                 SEQ ID 
                 Human ( Homo   
                 QAACPESWIGFQRKCFYFSDDTKNWTSSQRFCDSQDADLAQVESFQELNFLLRYKGPSDHWI 
               
               
                 895 
                   sapiens ) 
                 GLSREQGQPWKWINGTEWTRQFPILGAGECAYLNDKGASSAACAAAAAWICSKSDIHVEFE 
               
               
                   
                 CLEC2D 
                 QKLISEEDLDYKDDDDKENLYFQGLQASGGGGSGGGGSGGGGSQELTTICEQIPSPTLESTPYS 
               
               
                   
                 construct 10 
                 LSTTTILANGKAMQGVFEYYKSVTFVSNCGSHPSTTSKGSPINTQYVF 
               
               
                   
               
               
                 SEQ ID 
                 Human ( Homo   
                 QAACPESWIGFQRKCFYFSDDTKNWTSSQRFCDSQDADLAQVESFQELNFLLRYKGPSDHWI 
               
               
                 896 
                   sapiens ) 
                 GLSREQGQPWKWINGTEWTRQFPILGAGECAYLNDKGASSAACAAAAAWICSKSDIHVHHH 
               
               
                   
                 CLEC2D 
                 HHHHH 
               
               
                   
                 construct 11 
                   
               
               
                   
               
               
                 SEQ ID 
                 Human ( Homo   
                 MMSFVSLLLVGILFHATQAQAACPESWIGFQRKCFYFSDDTKNWTSSQRFCDSQDADLAQV 
               
               
                 897 
                   sapiens ) 
                 ESFQELNFLLRYKGPSDHWIGLSREQGQPWKWINGTEWTRQFPILGAGECAALADKGASSAR 
               
               
                   
                 CLEC2D 
                 CYTERKWICSKSDIHVHHHHHHHH 
               
               
                   
                 construct 12 
                   
               
               
                   
               
               
                 SEQ ID 
                 Human ( Homo   
                 QAACPESWIGFQRKCFYFSDDTKNWTSSQRFCDSQDADLAQVESFQELNFLLRYKGPSDHWI 
               
               
                 898 
                   sapiens ) 
                 GLSREQGQPWKWINGTEWTRQFPILGAGECAALADKGASSARCYTERKWICSKSDIHVHHH 
               
               
                   
                 CLEC2D 
                 HHHHH 
               
               
                   
                 construct 13 
                   
               
               
                   
               
               
                 SEQ ID 
                 Human ( Homo   
                 MQLLRCFSIFSVIASVLAQAACPESWIGFQRKCFYFSDDTKNWTSSQRFCDSQDADLAQVESF 
               
               
                 899 
                   sapiens ) 
                 QELNFLLRYKGPSDHWIGLSREQGQPWKWINGTEWTRQFPILGAGECAALADKGASSARCY 
               
               
                   
                 CLEC2D 
                 TERKWICSKSDIHVEFEQKLISEEDLDYKDDDDKENLYFQGLQASGGGGSGGGGSGGGGSQE 
               
               
                   
                 construct 14 
                 LTTICEQIPSPTLESTPYSLSTTTILANGKAMQGVFEYYKSVTFVSNCGSHPSTTSKGSPINTQYV 
               
               
                   
                   
                 F 
               
               
                   
               
               
                 SEQ ID 
                 Human ( Homo   
                 QAACPESWIGFQRKCFYFSDDTKNWTSSQRFCDSQDADLAQVESFQELNFLLRYKGPSDHWI 
               
               
                 900 
                   sapiens ) 
                 GLSREQGQPWKWINGTEWTRQFPILGAGECAALADKGASSARCYTERKWICSKSDIHVEFEQ 
               
               
                   
                 CLEC2D 
                 KLISEEDLDYKDDDDKENLYFQGLQASGGGGSGGGGSGGGGSQELTTICEQIPSPTLESTPYSL 
               
               
                   
                 construct 15 
                 STTTILANGKAMQGVFEYYKSVTFVSNCGSHPSTTSKGSPINTQYVF 
               
               
                   
               
               
                 SEQ ID 
                 Human ( Homo   
                 MMSFVSLLLVGILFHATQAQAACPESWIGFQRKCFYFSDDTKNWTSSQRFCDSQDADLAQV 
               
               
                 901 
                   sapiens ) 
                 ESFQELNFLLRYKGPSDHWIGLSREQGQPWKWINGTEWTRQFPILGAGECAYLNDAGAASA 
               
               
                   
                 CLEC2D 
                 RCYTERKWICSKSDIHVHHHHHHHH 
               
               
                   
                 construct 16 
                   
               
               
                   
               
               
                 SEQ ID 
                 Human ( Homo   
                 QAACPESWIGFQRKCFYFSDDTKNWTSSQRFCDSQDADLAQVESFQELNFLLRYKGPSDHWI 
               
               
                 902 
                   sapiens ) 
                 GLSREQGQPWKWINGTEWTRQFPILGAGECAYLNDAGAASARCYTERKWICSKSDIHVHHH 
               
               
                   
                 CLEC2D 
                 HHHHH 
               
               
                   
                 construct 17 
                   
               
               
                   
               
               
                 SEQ ID 
                 Human ( Homo   
                 MQLLRCFSIFSVIASVLAQAACPESWIGFQRKCFYFSDDTKNWTSSQRFCDSQDADLAQVESF 
               
               
                 903 
                   sapiens ) 
                 QELNFLLRYKGPSDHWIGLSREQGQPWKWINGTEWTRQFPILGAGECAYLNDAGAASARCY 
               
               
                   
                 CLEC2D 
                 TERKWICSKSDIHVEFEQKLISEEDLDYKDDDDKENLYFQGLQASGGGGSGGGGSGGGGSQE 
               
               
                   
                 construct 18 
                 LTTICEQIPSPTLESTPYSLSTTTILANGKAMQGVFEYYKSVTFVSNCGSHPSTTSKGSPINTQYV 
               
               
                   
                   
                 F 
               
               
                   
               
               
                 SEQ ID 
                 Human ( Homo   
                 QAACPESWIGFQRKCFYFSDDTKNWTSSQRFCDSQDADLAQVESFQELNFLLRYKGPSDHWI 
               
               
                 904 
                   sapiens ) 
                 GLSREQGQPWKWINGTEWTRQFPILGAGECAYLNDAGAASARCYTERKWICSKSDIHVEFEQ 
               
               
                   
                 CLEC2D 
                 KLISEEDLDYKDDDDKENLYFQGLQASGGGGSGGGGSGGGGSQELTTICEQIPSPTLESTPYSL 
               
               
                   
                 construct 19 
                 STTTILANGKAMQGVFEYYKSVTFVSNCGSHPSTTSKGSPINTQYVF 
               
               
                   
               
               
                 SEQ ID 
                 Human ( Homo   
                 MHDSNNVEKDITPSELPANPGCLHSKEHSIKATLIWRLFFLIMFLTIIVCGMVAALSAIRANCHQ 
               
               
                 905 
                   sapiens ) 
                 EPSVCLQAACPESWIGFQRKCFYFSDDTKNWTSSQRFCDSQDADLAQVESFQELNFLLRYKGP 
               
               
                   
                 CLEC2D 
                 SDHWIGLSREQGQPWKWINGTEWTRQLVMKEDGANLYVAKVSQVPRMNPRPVMVSYPG 
               
               
                   
                 construct 20 
                 SRRVCLFE 
               
               
                   
               
               
                 SEQ ID 
                 Human ( Homo   
                 MHDSNNVEKDITPSELPANPGCLHSKEHSIKATLIWRLFFLIMFLTIIVCGMVAALSAIRANCHQ 
               
               
                 906 
                   sapiens ) 
                 EPSVCLQAACPESWIGFQRKCFYFSDDTKNWTSSQRFCDSQDADLAQVESFQELNFLLRYKGP 
               
               
                   
                 CLEC2D 
                 SDHWIGLSREQGQPWKWINGTEWTRQ 
               
               
                   
                 construct 21 
                   
               
               
                   
               
               
                 SEQ ID 
                 Human ( Homo   
                 MHDSNNVEKDITPSELPANPGCLHSKEHSIKATLIWRLFFLIMFLTIIVCGMVAALSAIRANCHQ 
               
               
                 907 
                   sapiens ) 
                 EPSVCLQAACPESWIGFQRKCFYFSDDTKNWTSSQRFCDSQDADLAQVESFQELVSYPGSRR 
               
               
                   
                 CLEC2D 
                 VCLFE 
               
               
                   
                 construct 22 
                   
               
               
                   
               
               
                 SEQ ID 
                 Human ( Homo   
                 MHDSNNVEKDITPSELPANPAIRANCHQEPSVCLQAACPESWIGFQRKCFYFSDDTKNWTSS 
               
               
                 908 
                   sapiens ) 
                 QRFCDSQDADLAQVESFQELNFLLRYKGPSDHWIGLSREQGQPWKWINGTEWTRQFPILGA 
               
               
                   
                 CLEC2D 
                 GECAYLNDKGASSARHYTERKWICSKSDIHV 
               
               
                   
                 construct 23 
                   
               
               
                   
               
               
                 SEQ ID 
                 Human ( Homo   
                 MHDSNNVEKDITPSELPANPAIRANCHQEPSVCLQAACPESWIGFQRKCFYFSDDTKNWTSS 
               
               
                 909 
                   sapiens ) 
                 QRFCDSQDADLAQVESFQELVSYPGSRRVCLFE 
               
               
                   
                 CLEC2D 
                   
               
               
                   
                 construct 24 
                   
               
               
                   
               
               
                 SEQ ID 
                 Rat ( Rattus   
                 MPSSAHLQDPPPLLSRTLIQNEGQTSLRQSSSCGPSAASASESLSGSTESRIPHSKMLQGKLPR 
               
               
                 910 
                   norvegicus ) 
                 NIPLEYPAGLYCCYVVIIVLSVAVVALSVALSVKKTAQISTINTYAACPRNWIGVGNKCFYFNEIP 
               
               
                   
                 CLEC2D 
                 SNWTLSQTLCKEQGAELARFDTEEELNFLRRYKGSSGYWFGLHRESSAHPWKWTDNTEYNN 
               
               
                   
                 construct 1 
                 SVSIGGDEKHGFLSDNGFSSGRGYIVRKSICRKPNSYTSQCL 
               
               
                   
               
               
                 SEQ ID 
                 Mouse ( Mus   
                 MCVTKASLPMLSPTGSPQEVEVGKILQGKRHGTISPESCAKLYCYYGVIMVLTVAVIALSVALS 
               
               
                 911 
                   Musculus ) 
                 ATKTEQIPVNKTYAACPQNWIGVENKCFYFSEYPSNWTFAQAFCMAQEAQLARFDNQDELN 
               
               
                   
                 CLEC2D 
                 FLMRYKANFDSWIGLHRESSEHPWKWTDNTEYNNTIPIRGEERFAYLNNNGISSTRIYSLRM 
               
               
                   
                 construct 1 
                 WICSKLNSYSLHCQTPFFPS 
               
               
                   
               
               
                 SEQ ID 
                 Mouse ( Mus   
                 MSFVSLLLVGILFHATQAYAACPQNWIGVENKCFYFSEYPSNWTFAQAFCMAQEAQLARFD 
               
               
                 912 
                   Musculus ) 
                 NQDELNFLMRYKANFDSWIGLHRESSEHPWKWTDNTEYNNTIPIRGEERFAYLNNNGISSTRI 
               
               
                   
                 CLEC2D 
                 YSLRMWICSKLNSYSLHCQTPFFPSHHHHHHHH 
               
               
                   
                 construct 2 
                   
               
               
                   
               
               
                 SEQ ID 
                 Mouse ( Mus   
                 YAACPQNWIGVENKCFYFSEYPSNWTFAQAFCMAQEAQLARFDNQDELNFLMRYKANFDS 
               
               
                 913 
                   Musculus ) 
                 WIGLHRESSEHPWKWTDNTEYNNTIPIRGEERFAYLNNNGISSTRIYSLRMWICSKLNSYSLHC 
               
               
                   
                 CLEC2D 
                 QTPFFPSHHHHHHHH 
               
               
                   
                 construct 3 
                   
               
               
                   
               
               
                 SEQ ID 
                 Mouse ( Mus   
                 MSFVSLLLVGILFHATQAYAACPQNWIGVENKCFYFSEYPSNWTFAQAFCMAQEAQLARFD 
               
               
                 914 
                   Musculus ) 
                 NQDELNFLMRYKANFDSWIGLHRESSEHPWKWTDNTEYNNTIPIRGEERFAYLNNNGISSTR 
               
               
                   
                 CLEC2D 
                 CYSLRMWICSKLNSYSLHCQTPFFPSHHHHHHHH 
               
               
                   
                 construct 4 
                   
               
               
                   
               
               
                 SEQ ID 
                 Mouse ( Mus   
                 YAACPQNWIGVENKCFYFSEYPSNWTFAQAFCMAQEAQLARFDNQDELNFLMRYKANFDS 
               
               
                 915 
                   Musculus ) 
                 WIGLHRESSEHPWKWTDNTEYNNTIPIRGEERFAYLNNNGISSTRCYSLRMWICSKLNSYSLH 
               
               
                   
                 CLEC2D 
                 CQTPFFPSHHHHHHHH 
               
               
                   
                 construct 5 
                   
               
               
                   
               
               
                 SEQ ID 
                 Dog ( Canis   
                 MSFVSLLLVGILFHATQAEAACPESWIGFQRKCFYFSDDIKNWTFSQRFCDSYGADLVQIETLL 
               
               
                 916 
                 
                   lupus 
                 
                 ELNFLLRYKGPYDHWIGLSRDLGQPWKWVNGTEWTNCFPIRGGGECAYLNDKGASSARRYT 
               
               
                   
                   familiaris ) 
                 ERKWICSKPDIYAQIKRQNSIHHHHHHHH 
               
               
                   
                 CLEC2D 
                   
               
               
                   
                 construct 1 
                   
               
               
                   
               
               
                 SEQ ID 
                 Dog ( Canis   
                 EAACPESWIGFQRKCFYFSDDIKNWTFSQRFCDSYGADLVQIETLLELNFLLRYKGPYDHWIGL 
               
               
                 917 
                 
                   lupus 
                 
                 SRDLGQPWKWVNGTEWTNCFPIRGGGECAYLNDKGASSARRYTERKWICSKPDIYAQIKRQ 
               
               
                   
                   familiaris ) 
                 NSIHHHHHHHH 
               
               
                   
                 CLEC2D 
                   
               
               
                   
                 construct 2 
                   
               
               
                   
               
               
                 SEQ ID 
                 Cynomolgus 
                 MVTGSKMHDSNNVEKDIAPSELPANPGYRHSKQHSGKATLIWPLFFLIMFLTIIVCGMVVALS 
               
               
                 918 
                 ( Macaca   
                 AIRANCHQKPSVCLQAACPESWIGFQRKCFYFSDDTKNWTSSQRFCDSQDAALAQVESFQEL 
               
               
                   
                   fascicularis ) 
                 NFLLRYKGPSDHWIGLSREQGQPWKWINGTEWTRQFPILGAGEYAYLNDKGASSARYYTERK 
               
               
                   
                 CLEC2D 
                 WICSKPDTYVQMVQQSPN 
               
               
                   
                 construct 1 
                   
               
               
                   
               
               
                 SEQ ID 
                 Cynomolgus 
                 MSFVSLLLVGILFHATQAQAACPESWIGFQRKCFYFSDDTKNWTSSQRFCDSQDAALAQVES 
               
               
                 919 
                 ( Macaca   
                 FQELNFLLRYKGPSDHWIGLSREQGQPWKWINGTEWTRQFPILGAGEYAYLNDKGASSARYY 
               
               
                   
                   fascicularis ) 
                 TERKWICSKPDTYVQMVQQSPNHHHHHHHH 
               
               
                   
                 CLEC2D 
                   
               
               
                   
                 construct 2 
                   
               
               
                   
               
               
                 SEQ ID 
                 Cynomolgus 
                 QAACPESWIGFQRKCFYFSDDTKNWTSSQRFCDSQDAALAQVESFQELNFLLRYKGPSDHWI 
               
               
                 920 
                 ( Macaca   
                 GLSREQGQPWKWINGTEWTRQFPILGAGEYAYLNDKGASSARYYTERKWICSKPDTYVQMV 
               
               
                   
                   fascicularis ) 
                 QQSPNHHHHHHHH 
               
               
                   
                 CLEC2D 
                   
               
               
                   
                 construct 3 
                   
               
               
                   
               
               
                 SEQ ID 
                 Human ( Homo   
                 MDQQAIYAELNLPTDSGPESSSPSSLPRDVCQGSPWHQFALKLSCAGIILLVLVVTGLSVSVTSL 
               
               
                 921 
                   sapiens ) 
                 IQKSSIEKCSVDIQQSRNKTTERPGLLNCPIYWQQLREKCLLFSHTVNPWNNSLADCSTKESSLL 
               
               
                   
                 CD161 
                 LIRDKDELIHTQNLIRDKAILFWIGLNFSLSEKNWKWINGSFLNSNDLEIRGDAKENSCISISQTS 
               
               
                   
                 construct 1 
                 VYSEYCSTEIRWICQKELTPVRNKVYPDS 
               
               
                   
               
               
                 SEQ ID 
                 Human ( Homo   
                 MSFVSLLLVGILFHATQAQKSSIEKCSVDIQQSRNKTTERPGLLNCPIYWQQLREKCLLFSHTVN 
               
               
                 922 
                   sapiens ) 
                 PWNNSLADCSTKESSLLLIRDKDELIHTQNLIRDKAILFWIGLNFSLSEKNWKWINGSFLNSNDL 
               
               
                   
                 CD161 
                 EIRGDAKENSCISISQTSVYSEYCSTEIRWICQKELTPVRNKVYPDSHHHHHHHH 
               
               
                   
                 construct 2 
                   
               
               
                   
               
               
                 SEQ ID 
                 Human ( Homo   
                 QKSSIEKCSVDIQQSRNKTTERPGLLNCPIYWQQLREKCLLFSHTVNPWNNSLADCSTKESSLLL 
               
               
                 923 
                   sapiens ) 
                 IRDKDELIHTQNLIRDKAILFWIGLNFSLSEKNW 
               
               
                   
                 CD161 
                 KWINGSFLNSNDLEIRGDAKENSCISISQTSVYSEYCSTEIRWICQKELTPVRNKVYPDSHHHHH 
               
               
                   
                 construct 3 
                 HHH 
               
               
                   
               
               
                 SEQ ID 
                 Dog ( Canis   
                 MSFVSLLLVGILFHATQAQNSSIEECRVDVQVNGNETTEKPNLLQCPVHWHLLQEKCLFFSHA 
               
               
                 924 
                 
                   lupus 
                 
                 SNTWKDSLTDCSAKESSLLLIQDQEELRLIRGLIYKKEILFWIGLNLTLSEKKWKWINGSFLNSNIL 
               
               
                   
                   familiaris ) 
                 QIAGYNKESSCVYISLTGIVSENCDAENQWICQKELKPDRNKICSKFHHHHHHHH 
               
               
                   
                 CD161 
                   
               
               
                   
                 construct 1 
                   
               
               
                   
               
               
                 SEQ ID 
                 Dog ( Canis   
                 QNSSIEECRVDVQVNGNETTEKPNLLQCPVHWHLLQEKCLFFSHASNTWKDSLTDCSAKESSL 
               
               
                 925 
                 
                   lupus 
                 
                 LLIQDQEELRLIRGLIYKKEILFWIGLNLTLSEKKWKWINGSFLNSNILQIAGYNKESSCVYISLTGI 
               
               
                   
                   familiaris ) 
                 VSENCDAENQWICQKELKPDRNKICSKFHHHHHHHH 
               
               
                   
                 CD161 
                   
               
               
                   
                 construct 2 
                   
               
               
                   
               
               
                 SEQ ID 
                 Cynomolgus 
                 MSFVSLLLVGILFHATQAQKPSIGKCSVDIQQNRTKTTERPDLLNCPIYWQQVQEKCLLFSHTV 
               
               
                 926 
                 ( Macaca   
                 NPWNNSLADCSTKESSLLLIQDKDELTRTQNLIHDKAISFWIGLNFSLSEKNWKWINGSFLSSN 
               
               
                   
                   fascicularis ) 
                 DLKITGDAKENSCVYISQTSVYSEYCSTEMKWICQKELTLVRNKVSPDSWLHHHHHHHH 
               
               
                   
                 CD161 
                   
               
               
                   
                 construct 1 
                   
               
               
                   
               
               
                 SEQ ID 
                 Cynomolgus 
                 QKPSIGKCSVDIQQNRTKTTERPDLLNCPIYWQQVQEKCLLFSHTVNPWNNSLADCSTKESSL 
               
               
                 927 
                 ( Macaca   
                 LLIQDKDELTRTQNLIHDKAISFWIGLNFSLSEKNWKWINGSFLSSNDLKITGDAKENSCVYISQ 
               
               
                   
                   fascicularis ) 
                 TSVYSEYCSTEMKWICQKELTLVRNKVSPDSWLHHHHHHHH 
               
               
                   
                 CD161 
                   
               
               
                   
                 construct 2 
                   
               
               
                   
               
               
                 SEQ ID 
                 Mouse ( Mus   
                 MSFVSLLLVGILFHATQAQKPSREKCCVFIQENLNKTTDCSVNLECPQDWLLHRDKCFHVSQV 
               
               
                 928 
                   Musculus ) 
                 SNTWEEGQADCGRKGATLLLIQDQEELRFLLDSIKEKYNSFWIGLRFTLPDMNWKWINGTTF 
               
               
                   
                 CD161 
                 NSDVLKITGVTENGSCASILGDKVTPESCASDNRWICQKELNHETPSNDSHHHHHHHH 
               
               
                   
                 construct 1 
                   
               
               
                   
               
               
                 SEQ ID 
                 Mouse ( Mus   
                 QKPSREKCCVFIQENLNKTTDCSVNLECPQDWLLHRDKCFHVSQVSNTWEEGQADCGRKGA 
               
               
                 929 
                   Musculus ) 
                 TLLLIQDQEELRFLLDSIKEKYNSFWIGLRFTLPDMNWKWINGTTFNSDVLKITGVTENGSCASI 
               
               
                   
                 CD161 
                 LGDKVTPESCASDNRWICQKELNHETPSNDSHHHHHHHH 
               
               
                   
                 construct 2 
                   
               
               
                   
               
               
                 SEQ ID 
                 Human ( Homo   
                 MSFVSLLLVGILFHATQAQAACPESWIGFQRKCFYFSDDTKNWTSSQRFC 
               
               
                 930 
                   sapiens ) 
                 DSQDADLAQVESFQELNFLLRYKGaSDHWIGLSREQGQPWKWI 
               
               
                   
                 CLEC2D 
                 NGTEWTRQFPILGAGECAYLNDKGASSARCYTERKWICSKSDIH 
               
               
                   
                 construct 25 
                 VHHHHHHHH 
               
               
                   
               
               
                 SEQ ID 
                 Human ( Homo   
                 QAACPESWIGFQRKCFYFSDDTKNWTSSQRFCDSQDADLAQVE 
               
               
                 931 
                   sapiens ) 
                 SFQELNFLLRYKGaSDHWIGLSREQGQPWKWINGTEWTRQFPIL 
               
               
                   
                 CLEC2D 
                 GAGECAYLNDKGASSARCYTERKWICSKSDIHVHHHHHHHH 
               
               
                   
                 construct 26 
                   
               
               
                   
               
               
                 SEQ ID 
                 Human ( Homo   
                 MSFVSLLLVGILFHATQAQAACPESWIGFQRKCFYFSDDTKNWTSSQRFC 
               
               
                 932 
                   sapiens ) 
                 DSQDADLAQVESFQELNFLLRYKGPaDHWIGLSREQGQPWKWI 
               
               
                   
                 CLEC2D 
                 NGTEWTRQFPILGAGECAYLNDKGASSARCYTERKWICSKSDIH 
               
               
                   
                 construct 27 
                 VHHHHHHHH 
               
               
                   
               
               
                 SEQ ID 
                 Human ( Homo   
                 QAACPESWIGFQRKCFYFSDDTKNWTSSQRFCDSQDADLAQVE 
               
               
                 933 
                   sapiens ) 
                 SFQELNFLLRYKGPaDHWIGLSREQGQPWKWINGTEWTRQFPIL 
               
               
                   
                 CLEC2D 
                 GAGECAYLNDKGASSARCYTERKWICSKSDIHVHHHHHHHH 
               
               
                   
                 construct 28 
                   
               
               
                   
               
               
                 SEQ ID 
                 Human ( Homo   
                 MSFVSLLLVGILFHATQAQAACPESWIGFQRKCFYFSDDTKNWTSSQRFC 
               
               
                 934 
                   sapiens ) 
                 DSQDADLAQVESFQELNFLLRYKGPSaHWIGLSREQGQPWKWI 
               
               
                   
                 CLEC2D 
                 NGTEWTRQFPILGAGECAYLNDKGASSARCYTERKWICSKSDIH 
               
               
                   
                 construct 29 
                 VHHHHHHHH 
               
               
                   
               
               
                 SEQ ID 
                 Human ( Homo   
                 QAACPESWIGFQRKCFYFSDDTKNWTSSQRFCDSQDADLAQVE 
               
               
                 935 
                   sapiens ) 
                 SFQELNFLLRYKGPSaHWIGLSREQGQPWKWINGTEWTRQFPIL 
               
               
                   
                 CLEC2D 
                 GAGECAYLNDKGASSARCYTERKWICSKSDIHVHHHHHHHH 
               
               
                   
                 construct 30 
                   
               
               
                   
               
               
                 SEQ ID 
                 Human ( Homo   
                 MSFVSLLLVGILFHATQAQAACPESWIGFQRKCFYFSDDTKNWTSSQRFC 
               
               
                 936 
                   sapiens ) 
                 DSQDADLAQVESFQELNFLLRYKGPSDHWIGLSREaGQPWKWI 
               
               
                   
                 CLEC2D 
                 NGTEWTRQFPILGAGECAYLNDKGASSARCYTERKWICSKSDIH 
               
               
                   
                 construct 31 
                 VHHHHHHHH 
               
               
                   
               
               
                 SEQ ID 
                 Human ( Homo   
                 QAACPESWIGFQRKCFYFSDDTKNWTSSQRFCDSQDADLAQVE 
               
               
                 937 
                   sapiens ) 
                 SFQELNFLLRYKGPSDHWIGLSREaGQPWKWINGTEWTRQFPIL 
               
               
                   
                 CLEC2D 
                 GAGECAYLNDKGASSARCYTERKWICSKSDIHVHHHHHHHH 
               
               
                   
                 construct 32 
                   
               
               
                   
               
               
                 SEQ ID 
                 Human ( Homo   
                 MSFVSLLLVGILFHATQAQAACPESWIGFQRKCFYFSDDTKNWTSSQRFC 
               
               
                 938 
                   sapiens ) 
                 DSQDADLAQVESFQELNFLLRYKGPSDHWIGLSREQGQPWKWI 
               
               
                   
                 CLEC2D 
                 NGTEWTRQFPILGAGaCAYLNDKGASSARCYTERKWICSKSDIH 
               
               
                   
                 construct 33 
                 VHHHHHHHH 
               
               
                   
               
               
                 SEQ ID 
                 Human ( Homo   
                 QAACPESWIGFQRKCFYFSDDTKNWTSSQRFCDSQDADLAQVE 
               
               
                 939 
                   sapiens ) 
                 SFQELNFLLRYKGPSDHWIGLSREQGQPWKWINGTEWTRQFPIL 
               
               
                   
                 CLEC2D 
                 GAGaCAYLNDKGASSARCYTERKWICSKSDIHVHHHHHHHH 
               
               
                   
                 construct 34 
                   
               
               
                   
               
               
                 SEQ ID 
                 Human ( Homo   
                 MSFVSLLLVGILFHATQAQAACPESWIGFQRKCFYFSDDTKNWTSSQRFC 
               
               
                 940 
                   sapiens ) 
                 DSQDADLAQVESFQELNFLLRYKGPSDHWIGLSREQGQPWKWI 
               
               
                   
                 CLEC2D 
                 NGTEWTRQFPILGAGECAaLNDKGASSARCYTERKWICSKSDIH 
               
               
                   
                 construct 35 
                 VHHHHHHHH 
               
               
                   
               
               
                 SEQ ID 
                 Human ( Homo   
                 QAACPESWIGFQRKCFYFSDDTKNWTSSQRFCDSQDADLAQVE 
               
               
                 941 
                   sapiens ) 
                 SFQELNFLLRYKGPSDHWIGLSREQGQPWKWINGTEWTRQFPIL 
               
               
                   
                 CLEC2D 
                 GAGECAaLNDKGASSARCYTERKWICSKSDIHVHHHHHHHH 
               
               
                   
                 construct 36 
                   
               
               
                   
               
               
                 SEQ ID 
                 Human ( Homo   
                 MSFVSLLLVGILFHATQAQAACPESWIGFQRKCFYFSDDTKNWTSSQRFC 
               
               
                 942 
                   sapiens ) 
                 DSQDADLAQVESFQELNFLLRYKGPSDHWIGLSREQGQPWKWI 
               
               
                   
                 CLEC2D 
                 NGTEWTRQFPILGAGECAYLNDaGASSARCYTERKWICSKSDIHV 
               
               
                   
                 construct 37 
                 HHHHHHHH 
               
               
                   
               
               
                 SEQ ID 
                 Human ( Homo   
                 QAACPESWIGFQRKCFYFSDDTKNWTSSQRFCDSQDADLAQVE 
               
               
                 943 
                   sapiens ) 
                 SFQELNFLLRYKGPSDHWIGLSREQGQPWKWINGTEWTRQFPIL 
               
               
                   
                 CLEC2D 
                 GAGECAYLNDaGASSARCYTERKWICSKSDIHVHHHHHHHH 
               
               
                   
                 construct 38 
                   
               
               
                   
               
               
                 SEQ ID 
                 Human ( Homo   
                 MSFVSLLLVGILFHATQAQAACPESWIGFQRKCFYFSDDTKNWTSSQRFC 
               
               
                 944 
                   sapiens ) 
                 DSQDADLAQVESFQELNFLLRYKGPSDHWIGLSREQGQPWKWI 
               
               
                   
                 CLEC2D 
                 NGTEWTRQFPILGAGECAYLNDKGASaARCYTERKWICSKSDIH 
               
               
                   
                 construct 39 
                 VHHHHHHHH 
               
               
                   
               
               
                 SEQ ID 
                 Human ( Homo   
                 QAACPESWIGFQRKCFYFSDDTKNWTSSQRFCDSQDADLAQVE 
               
               
                 945 
                   sapiens ) 
                 SFQELNFLLRYKGPSDHWIGLSREQGQPWKWINGTEWTRQFPIL 
               
               
                   
                 CLEC2D 
                 GAGECAYLNDKGASaARCYTERKWICSKSDIHVHHHHHHHH 
               
               
                   
                 construct 40 
                   
               
               
                   
               
               
                 SEQ ID 
                 Human ( Homo   
                 MSFVSLLLVGILFHATQAQAACPESWIGFQRKCFYFSDDTKNWTSSQRFC 
               
               
                 946 
                   sapiens ) 
                 DSQDADLAQVESFQELNFLLRYKGPSDHWIGLSREQGQPWKWI 
               
               
                   
                 CLEC2D 
                 NGTEWTRQFPILGAGECAYLNDKGASSAaCYTERKWICSKSDIHV 
               
               
                   
                 construct 41 
                 HHHHHHHH 
               
               
                   
               
               
                 SEQ ID 
                 Human ( Homo   
                 QAACPESWIGFQRKCFYFSDDTKNWTSSQRFCDSQDADLAQVE 
               
               
                 947 
                   sapiens ) 
                 SFQELNFLLRYKGPSDHWIGLSREQGQPWKWINGTEWTRQFPIL 
               
               
                   
                 CLEC2D 
                 GAGECAYLNDKGASSAaCYTERKWICSKSDIHVHHHHHHHH 
               
               
                   
                 construct 42 
                   
               
               
                   
               
               
                 SEQ ID 
                 Human ( Homo   
                 MSFVSLLLVGILFHATQAQAACPESWIGFQRKCFYFSDDTKNWTSSQRFC 
               
               
                 948 
                   sapiens ) 
                 DSQDADLAQVESFQELNFLLRYKGPSDHWIGLSREQGQPWKWI 
               
               
                   
                 CLEC2D 
                 NGTEWTRQFPILGAGECAYLNDKGASSARCaTERKWICSKSDIH 
               
               
                   
                 construct 43 
                 VHHHHHHHH 
               
               
                   
               
               
                 SEQ ID 
                 Human ( Homo   
                 QAACPESWIGFQRKCFYFSDDTKNWTSSQRFCDSQDADLAQVE 
               
               
                 949 
                   sapiens ) 
                 SFQELNFLLRYKGPSDHWIGLSREQGQPWKWINGTEWTRQFPIL 
               
               
                   
                 CLEC2D 
                 GAGECAYLNDKGASSARCaTERKWICSKSDIHVHHHHHHHH 
               
               
                   
                 construct 44 
                   
               
               
                   
               
               
                 SEQ ID 
                 Human ( Homo   
                 MSFVSLLLVGILFHATQAQAACPESWIGFQRKCFYFSDDTKNWTSSQRFC 
               
               
                 950 
                   sapiens ) 
                 DSQDADLAQVESFQELNFLLRYKGPSDHWIGLSREQGQPWKWI 
               
               
                   
                 CLEC2D 
                 NGTEWTRQFPILGAGECAYLNDKGASSARCYaERKWICSKSDIH 
               
               
                   
                 construct 45 
                 VHHHHHHHH 
               
               
                   
               
               
                 SEQ ID 
                 Human ( Homo   
                 QAACPESWIGFQRKCFYFSDDTKNWTSSQRFCDSQDADLAQVE 
               
               
                 951 
                   sapiens ) 
                 SFQELNFLLRYKGPSDHWIGLSREQGQPWKWINGTEWTRQFPIL 
               
               
                   
                 CLEC2D 
                 GAGECAYLNDKGASSARCYaERKWICSKSDIHVHHHHHHHH 
               
               
                   
                 construct 46 
                   
               
               
                   
               
               
                 SEQ ID 
                 Human ( Homo   
                 MSFVSLLLVGILFHATQAQAACPESWIGFQRKCFYFSDDTKNWTSSQRFC 
               
               
                 952 
                   sapiens ) 
                 DSQDADLAQVESFQELNFLLRYKGPSDHWIGLSREQGQPWKWI 
               
               
                   
                 CLEC2D 
                 NGTEWTRQFPILGAGECAYLNDKGASSARCYTaRKWICSKSDIH 
               
               
                   
                 construct 47 
                 VHHHHHHHH 
               
               
                   
               
               
                 SEQ ID 
                 Human ( Homo   
                 QAACPESWIGFQRKCFYFSDDTKNWTSSQRFCDSQDADLAQVE 
               
               
                 953 
                   sapiens ) 
                 SFQELNFLLRYKGPSDHWIGLSREQGQPWKWINGTEWTRQFPIL 
               
               
                   
                 CLEC2D 
                 GAGECAYLNDKGASSARCYTaRKWICSKSDIHVHHHHHHHH 
               
               
                   
                 construct 48 
                   
               
               
                   
               
               
                 SEQ ID 
                 Human ( Homo   
                 MSFVSLLLVGILFHATQAQAACPESWIGFQRKCFYFSDDTKNWTSSQRFC 
               
               
                 954 
                   sapiens ) 
                 DSQDADLAQVESFQELNFLLRYKGPSDHWIGLSREQGQPWKWI 
               
               
                   
                 CLEC2D 
                 NGTEWTRQFPILGAGECAYLNDKGASSARCYTEaKWICSKSDIHV 
               
               
                   
                 construct 49 
                 HHHHHHHH 
               
               
                   
               
               
                 SEQ ID 
                 Human ( Homo   
                 QAACPESWIGFQRKCFYFSDDTKNWTSSQRFCDSQDADLAQVE 
               
               
                 955 
                   sapiens ) 
                 SFQELNFLLRYKGPSDHWIGLSREQGQPWKWINGTEWTRQFPIL 
               
               
                   
                 CLEC2D 
                 GAGECAYLNDKGASSARCYTEaKWICSKSDIHVHHHHHHHH 
               
               
                   
                 construct 50 
                   
               
               
                   
               
               
                 SEQ ID 
                 Human ( Homo   
                 MSFVSLLLVGILFHATQAQAACPESWIGFQRKCFYFSDDTKNWTSSQRFC 
               
               
                 956 
                   sapiens ) 
                 DSQDADLAQVESFQELNFLLRYKGPSDHWIGLSREQGQPWKWI 
               
               
                   
                 CLEC2D 
                 NGTEWTRQFPILGAGECAYLNDKGASSARCYTERaWICSKSDIHV 
               
               
                   
                 construct 51 
                 HHHHHHHH 
               
               
                   
               
               
                 SEQ ID 
                 Human ( Homo   
                 QAACPESWIGFQRKCFYFSDDTKNWTSSQRFCDSQDADLAQVE 
               
               
                 957 
                   sapiens ) 
                 SFQELNFLLRYKGPSDHWIGLSREQGQPWKWINGTEWTRQFPIL 
               
               
                   
                 CLEC2D 
                 GAGECAYLNDKGASSARCYTERaWICSKSDIHVHHHHHHHH 
               
               
                   
                 construct 52 
                   
               
               
                   
               
               
                 SEQ ID 
                 Human ( Homo   
                 MSFVSLLLVGILFHATQAQAACPESWIGFQRKCFYFSDDTKNWTSSQRFC 
               
               
                 958 
                   sapiens ) 
                 DSQDADLAQVESFQELNFLLRYKGPSDHWIGLSREQGQPWKWI 
               
               
                   
                 CLEC2D 
                 NGTEWTRQFPILGAGECAALADaGAaSARCYTERKWICSKSDIH 
               
               
                   
                 construct 53 
                 VHHHHHHH 
               
               
                   
               
               
                 SEQ ID 
                 Human ( Homo   
                 QAACPESWIGFQRKCFYFSDDTKNWTSSQRFCDSQDADLAQVE 
               
               
                 959 
                   sapiens ) 
                 SFQELNFLLRYKGPSDHWIGLSREQGQPWKWINGTEWTRQFPIL 
               
               
                   
                 CLEC2D 
                 GAGECAALADaGAaSARCYTERKWICSKSDIHVHHHHHHH 
               
               
                   
                 construct 54 
                   
               
               
                   
               
               
                 SEQ ID 
                 Human ( Homo   
                 MSFVSLLLVGILFHATQAQAACPESWIGFQRKCFYFSDDTKNWTSSQRFC 
               
               
                 960 
                   sapiens ) 
                 DSQDADLAQVESFQELNFLLRYKGPSDHWIGLSREQGQPWKWI 
               
               
                   
                 CLEC2D 
                 NGTEWTRQFPILGAGECAaLaDAGAASARCYTERKWICSKSDIH 
               
               
                   
                 construct 55 
                 VHHHHHHH 
               
               
                   
               
               
                 SEQ ID 
                 Human ( Homo   
                 QAACPESWIGFQRKCFYFSDDTKNWTSSQRFCDSQDADLAQVE 
               
               
                 961 
                   sapiens ) 
                 SFQELNFLLRYKGPSDHWIGLSREQGQPWKWINGTEWTRQFPIL 
               
               
                   
                 CLEC2D 
                 GAGECAaLaDAGAASARCYTERKWICSKSDIHVHHHHHHH 
               
               
                   
                 construct 56 
                   
               
               
                   
               
               
                 SEQ ID 
                 Human ( Homo   
                 MSFVSLLLVGILFHATQAQAACPESWIGFQRKCFYFSDDTKNWTSSQaFC 
               
               
                 962 
                   sapiens ) 
                 DSQDADLAQVESFQELNFLLRYKGPSDHWIGLSREQGQPWKWI 
               
               
                   
                 CLEC2D 
                 NGTEWTRQFPILGAGECAYLNDKGASSARCYTERKWICSKSDIH 
               
               
                   
                 construct 57 
                 VHHHHHHHH 
               
               
                   
               
               
                 SEQ ID 
                 Human ( Homo   
                 QAACPESWIGFQRKCFYFSDDTKNWTSSQaFCDSQDADLAQVES 
               
               
                 963 
                   sapiens ) 
                 FQELNFLLRYKGPSDHWIGLSREQGQPWKWINGTEWTRQFPILG 
               
               
                   
                 CLEC2D 
                 AGECAYLNDKGASSARCYTERKWICSKSDIHVHHHHHHHH 
               
               
                   
                 construct 58 
                   
               
               
                   
               
               
                 SEQ ID 
                 Human ( Homo   
                 MSFVSLLLVGILFHATQAQAACPESWIGFQRKCFYFSDDTKNWTSSQRFC 
               
               
                 964 
                   sapiens ) 
                 DSQDADLAQVESFQELNFLLRYKGPSDHWIGLSREQGaPWKWI 
               
               
                   
                 CLEC2D 
                 NGTEWTRQFPILGAGECAYLNDKGASSARCYTERKWICSKSDIH 
               
               
                   
                 construct 59 
                 VHHHHHHHH 
               
               
                   
               
               
                 SEQ ID 
                 Human ( Homo   
                 QAACPESWIGFQRKCFYFSDDTKNWTSSQRFCDSQDADLAQVE 
               
               
                 965 
                   sapiens ) 
                 SFQELNFLLRYKGPSDHWIGLSREQGaPWKWINGTEWTRQFPIL 
               
               
                   
                 CLEC2D 
                 GAGECAYLNDKGASSARCYTERKWICSKSDIHVHHHHHHHH 
               
               
                   
                 construct 60 
                   
               
               
                   
               
               
                 SEQ ID 
                 Human ( Homo   
                 MSFVSLLLVGILFHATQAQAACPESWIGFQRKCFYFSDDTKNWTSSQRFC 
               
               
                 966 
                   sapiens ) 
                 DSQDADLAQVESFQELNFLLRYKGPSDHWIGLSREQGQPWKWI 
               
               
                   
                 CLEC2D 
                 NGTEWTaQFPILGAGECAYLNDKGASSARCYTERKWICSKSDIHV 
               
               
                   
                 construct 61 
                 HHHHHHHH 
               
               
                   
               
               
                 SEQ ID 
                 Human ( Homo   
                 QAACPESWIGFQRKCFYFSDDTKNWTSSQRFCDSQDADLAQVE 
               
               
                 967 
                   sapiens ) 
                 SFQELNFLLRYKGPSDHWIGLSREQGQPWKWINGTEWTaQFPIL 
               
               
                   
                 CLEC2D 
                 GAGECAYLNDKGASSARCYTERKWICSKSDIHVHHHHHHHH 
               
               
                   
                 construct 62 
                   
               
               
                   
               
               
                 SEQ ID 
                 Human ( Homo   
                 MSFVSLLLVGILFHATQAQAACPESWIGFQRKCFYFSDDTKNWTSSQRFC 
               
               
                 968 
                   sapiens ) 
                 DSQDADLAQVESFQELNFLLRYKGPSDHWIGLSREQGQPWKWI 
               
               
                   
                 CLEC2D 
                 NGTEWTRQFPILGAGECAYLNDKGASSARCYTERKWICSKaDIH 
               
               
                   
                 construct 63 
                 VHHHHHHHH 
               
               
                   
               
               
                 SEQ ID 
                 Human ( Homo   
                 QAACPESWIGFQRKCFYFSDDTKNWTSSQRFCDSQDADLAQVE 
               
               
                 969 
                   sapiens ) 
                 SFQELNFLLRYKGPSDHWIGLSREQGQPWKWINGTEWTRQFPIL 
               
               
                   
                 CLEC2D 
                 GAGECAYLNDKGASSARCYTERKWICSKaDIHVHHHHHHHH 
               
               
                   
                 construct 64 
                   
               
               
                   
               
               
                 SEQ ID 
                 Human ( Homo   
                 MSFVSLLLVGILFHATQAQAACPESWIGFQRKCFYFSDDTKNWTSSQRFC 
               
               
                 970 
                   sapiens ) 
                 DSQDADLAQVESFQELNFLLRYKGPSDHWIGLSREQGQPWKWI 
               
               
                   
                 CLEC2D 
                 NGTEWIRQFPILGAGECAYLNDKGASSARCYTERKWICSKSDIaV 
               
               
                   
                 construct 65 
                 HHHHHHHH 
               
               
                   
               
               
                 SEQ ID 
                 Human ( Homo   
                 QAACPESWIGFQRKCFYFSDDTKNWTSSQRFCDSQDADLAQVE 
               
               
                 971 
                   sapiens ) 
                 SFQELNFLLRYKGPSDHWIGLSREQGQPWKWINGTEWTRQFPIL 
               
               
                   
                 CLEC2D 
                 GAGECAYLNDKGASSARCYTERKWICSKSDIaVHHHHHHHH 
               
               
                   
                 construct 66 
                   
               
               
                   
               
               
                 SEQ ID 
                 Human ( Homo   
                 MSFVSLLLVGILFHATQAQAACPESWIGFQRKCFYFSDDTKNWTSSQRFC 
               
               
                 972 
                   sapiens ) 
                 DSQDADLAQVESFQELNFLLRYKGPSDHWIGLSREQGQPWKWI 
               
               
                   
                 CLEC2D 
                 NGTEWTRQFPILGAGECAYLNDKGASSAaCaTaRKWICSKSDIHV 
               
               
                   
                 construct 67 
                 HHHHHHHH 
               
               
                   
               
               
                 SEQ ID 
                 Human ( Homo   
                 QAACPESWIGFQRKCFYFSDDTKNWTSSQRFCDSQDADLAQVE 
               
               
                 973 
                   sapiens ) 
                 SFQELNFLLRYKGPSDHWIGLSREQGQPWKWINGTEWTRQFPIL 
               
               
                   
                 CLEC2D 
                 GAGECAYLNDKGASSAaCaTaRKWICSKSDIHVHHHHHHHH 
               
               
                   
                 construct 68 
                   
               
               
                   
               
               
                 SEQ ID 
                 Human ( Homo   
                 MSFVSLLLVGILFHATQAQAACPESWIGFQaKCFYFSDDTKNWTSSQRFC 
               
               
                 974 
                   sapiens ) 
                 DSQDADLAQVESFQELNFLLRYKGPSDHWIGLSREQGQPWKWI 
               
               
                   
                 CLEC2D 
                 NGTEWIRQFPILGAGECAYLNDKGASSARCYTERKWICSKSDIaV 
               
               
                   
                 construct 69 
                 HHHHHHHH 
               
               
                   
               
               
                 SEQ ID 
                 Human ( Homo   
                 QAACPESWIGFQaKCFYFSDDTKNWTSSQRFCDSQDADLAQVES 
               
               
                 975 
                   sapiens ) 
                 FQELNFLLRYKGPSDHWIGLSREQGQPWKWINGTEWTRQFPILG 
               
               
                   
                 CLEC2D 
                 AGECAYLNDKGASSARCYTERKWICSKSDIaVHHHHHHHH 
               
               
                   
                 construct 70 
                   
               
               
                   
               
               
                 SEQ ID 
                 Human ( Homo   
                 MSFVSLLLVGILFHATQAQAACPESWIGFQRKCFYFSDDTKNWTSSQRFC 
               
               
                 976 
                   sapiens ) 
                 DSQDADLAQVESFQELNFLLRYKGPSDHWIGLSREQGQPWKWI 
               
               
                   
                 CLEC2D 
                 NGTaWaaaFPILGAGECAYLNDKGASSARCYTERKWICSKSDIHV 
               
               
                   
                 construct 71 
                 HHHHHHHH 
               
               
                   
               
               
                 SEQ ID 
                 Human ( Homo   
                 QAACPESWIGFQRKCFYFSDDTKNWTSSQRFCDSQDADLAQVE 
               
               
                 977 
                   sapiens ) 
                 SFQELNFLLRYKGPSDHWIGLSREQGQPWKWINGTaWaaaFPIL 
               
               
                   
                 CLEC2D 
                 GAGECAYLNDKGASSARCYTERKWICSKSDIHVHHHHHHHH 
               
               
                   
                 construct 72 
                   
               
               
                   
               
               
                 SEQ ID 
                 Human ( Homo   
                 MSFVSLLLVGILFHATQAQAACPESWIGFQRKCFYFSDDTKNWTSSQaFC 
               
               
                 978 
                   sapiens ) 
                 DaQDADLAQVESFQELNFLLRYKGPSDHWIGLSREQGQPWKWI 
               
               
                   
                 CLEC2D 
                 NGTEWTRQFPILGAGECAYLNDKGASSARCYTERKWICSKSDIH 
               
               
                   
                 construct 73 
                 VHHHHHHHH 
               
               
                   
               
               
                 SEQ ID 
                 Human ( Homo   
                 QAACPESWIGFQRKCFYFSDDTKNWTSSQaFCDaQDADLAQVES 
               
               
                 979 
                   sapiens ) 
                 FQELNFLLRYKGPSDHWIGLSREQGQPWKWINGTEWTRQFPILG 
               
               
                   
                 CLEC2D 
                 AGECAYLNDKGASSARCYTERKWICSKSDIHVHHHHHHHH 
               
               
                   
                 construct 74 
                   
               
               
                   
               
               
                 SEQ ID 
                 Human ( Homo   
                 MSFVSLLLVGILFHATQAQAACPESWIGFQRKCFYFSDDTKNWTSSQRFC 
               
               
                 980 
                   sapiens ) 
                 DSQaADLAQVESFQELNFLLRYKGPSDHWIGLSREQGQPWKWI 
               
               
                   
                 CLEC2D 
                 NGTEWIRQFPILGAGECAYLNDKGASSARCYTERKWICSKSDIaV 
               
               
                   
                 construct 75 
                 HHHHHHHH 
               
               
                   
               
               
                 SEQ ID 
                 Human ( Homo   
                 QAACPESWIGFQRKCFYFSDDTKNWTSSQRFCDSQaADLAQVES 
               
               
                 981 
                   sapiens ) 
                 FQELNFLLRYKGPSDHWIGLSREQGQPWKWINGTEWTRQFPILG 
               
               
                   
                 CLEC2D 
                 AGECAYLNDKGASSARCYTERKWICSKSDIaVHHHHHHHH 
               
               
                   
                 construct 76 
                   
               
               
                   
               
               
                 SEQ ID 
                 Human ( Homo   
                 MSFVSLLLVGILFHATQAQAACPESWIGFQRKCFYFSDDTKNWTSSQRFC 
               
               
                 982 
                   sapiens ) 
                 DSQDADLAQVESFQELNFLLRYKGPSDHWIGLSREQGaPWKWI 
               
               
                   
                 CLEC2D 
                 NGTEWTaQFPILGAGECAYLNDKGASSARCYTERKWICSKSDIHV 
               
               
                   
                 construct 77 
                 HHHHHHHH 
               
               
                   
               
               
                 SEQ ID 
                 Human ( Homo   
                 QAACPESWIGFQRKCFYFSDDTKNWTSSQRFCDSQDADLAQVE 
               
               
                 983 
                   sapiens ) 
                 SFQELNFLLRYKGPSDHWIGLSREQGaPWKWINGTEWTaQFPIL 
               
               
                   
                 CLEC2D 
                 GAGECAYLNDKGASSARCYTERKWICSKSDIHVHHHHHHHH 
               
               
                   
                 construct 78 
                   
               
               
                   
               
               
                 SEQ ID 
                 Human ( Homo   
                 MSFVSLLLVGILFHATQAQAACPESWIGFQRKCFYFSDaaaNWTSSQRFC 
               
               
                 984 
                   sapiens ) 
                 DSQDADLAQVESFQELNFLLRYKGPSDHWIGLSREQGQPWKWI 
               
               
                   
                 CLEC2D 
                 NGTEWTRQFPILGAGECAYLNDKGASSARCYTERKWICSKSDIH 
               
               
                   
                 construct 79 
                 VHHHHHHHH 
               
               
                   
               
               
                 SEQ ID 
                 Human ( Homo   
                 QAACPESWIGFQRKCFYFSDaaaNWTSSQRFCDSQDADLAQVES 
               
               
                 985 
                   sapiens ) 
                 FQELNFLLRYKGPSDHWIGLSREQGQPWKWINGTEWTRQFPILG 
               
               
                   
                 CLEC2D 
                 AGECAYLNDKGASSARCYTERKWICSKSDIHVHHHHHHHH 
               
               
                   
                 construct 80 
                   
               
               
                   
               
               
                 SEQ ID 
                 Human ( Homo   
                 MSFVSLLLVGILFHATQAQAACPESWIGFQRKCFYFSDDTKNWTSSQRFC 
               
               
                 986 
                   sapiens ) 
                 DSQDADLAQVESFQELNFLLRYKGPSDHWIGLSREQGaPWaWIN 
               
               
                   
                 CLEC2D 
                 GTEWTRQFPILGAGECAYLNDKGASSARCYTERKWICSKSDIHV 
               
               
                   
                 construct 81 
                 HHHHHHHH 
               
               
                   
               
               
                 SEQ ID 
                 Human ( Homo   
                 QAACPESWIGFQRKCFYFSDDTKNWTSSQRFCDSQDADLAQVE 
               
               
                 987 
                   sapiens ) 
                 SFQELNFLLRYKGPSDHWIGLSREQGaPWaWINGTEWTRQFPIL 
               
               
                   
                 CLEC2D 
                 GAGECAYLNDKGASSARCYTERKWICSKSDIHVHHHHHHHH 
               
               
                   
                 construct 82 
                   
               
               
                   
               
               
                 SEQ ID 
                 Human ( Homo   
                 MSFVSLLLVGILFHATQAQAACPESWIGFQRKCFYFSDDTKNWTSSQRFC 
               
               
                 988 
                   sapiens ) 
                 DSQDADLAQVESFQELNFLLRYKGPSDHWIGLSRaQGQPWKWI 
               
               
                   
                 CLEC2D 
                 NGTEWTRQFPILGAGECAYLNDKGASSARaYTERKWICSKSDIHV 
               
               
                   
                 construct 83 
                 HHHHHHHH 
               
               
                   
               
               
                 SEQ ID 
                 Human ( Homo   
                 QAACPESWIGFQRKCFYFSDDTKNWTSSQRFCDSQDADLAQVE 
               
               
                 989 
                   sapiens ) 
                 SFQELNFLLRYKGPSDHWIGLSRaQGQPWKWINGTEWTRQFPIL 
               
               
                   
                 CLEC2D 
                 GAGECAYLNDKGASSARaYTERKWICSKSDIHVHHHHHHHH 
               
               
                   
                 construct 84 
                   
               
               
                   
               
               
                 SEQ ID 
                 Human ( Homo   
                 MSFVSLLLVGILFHATQAQAACPESWIGFQRKCFYFSDDTKNWTSSQRFC 
               
               
                 990 
                   sapiens ) 
                 DSQDADLAQVESFQELNFLLRYKGPSDHWIGLSRaaGaPWKWIN 
               
               
                   
                 CLEC2D 
                 GTEWTRQFPILGAGECAYLNDKGASSAaCYTERKWICSKSDIHVH 
               
               
                   
                 construct 85 
                 HHHHHHH 
               
               
                   
               
               
                 SEQ ID 
                 Human ( Homo   
                 QAACPESWIGFQRKCFYFSDDTKNWTSSQRFCDSQDADLAQVE 
               
               
                 991 
                   sapiens ) 
                 SFQELNFLLRYKGPSDHWIGLSRaaGaPWKWINGTEWTRQFPIL 
               
               
                   
                 CLEC2D 
                 GAGECAYLNDKGASSAaCYTERKWICSKSDIHVHHHHHHHH 
               
               
                   
                 construct 86 
                   
               
               
                   
               
               
                 SEQ ID 
                 Human ( Homo   
                 MSFVSLLLVGILFHATQAQAACPESWIGFQRKCFYFSDaTKNWTSSQRFC 
               
               
                 992 
                   sapiens ) 
                 DSQDADLAQVESFQELNFLLRYKGPSDHWIGLSREQGQPWKWI 
               
               
                   
                 CLEC2D 
                 NGTEWTRQFPILGAGECAYLNDKGASSARCaTERaWICSKSDIHV 
               
               
                   
                 construct 87 
                 HHHHHHHH 
               
               
                   
               
               
                 SEQ ID 
                 Human ( Homo   
                 QAACPESWIGFQRKCFYFSDaTKNWTSSQRFCDSQDADLAQVES 
               
               
                 993 
                   sapiens ) 
                 FQELNFLLRYKGPSDHWIGLSREQGQPWKWINGTEWTRQFPILG 
               
               
                   
                 CLEC2D 
                 AGECAYLNDKGASSARCaTERaWICSKSDIHVHHHHHHHH 
               
               
                   
                 construct 88 
                   
               
               
                   
               
               
                 SEQ ID 
                 Human ( Homo   
                 MSFVSLLLVGILFHATQAQAACPESWIGFQRKCFYFSDDTKNWTSSQRFC 
               
               
                 994 
                   sapiens ) 
                 DSQDADLAQVESaQELNFLLRYKGPSDHWIGLSREQGQPWKWI 
               
               
                   
                 CLEC2D 
                 NGTEWTaQFPILGAGECAYLNDKGASSARCYTERKWICSKSDIHV 
               
               
                   
                 construct 89 
                 HHHHHHHH 
               
               
                   
               
               
                 SEQ ID 
                 Human ( Homo   
                 QAACPESWIGFQRKCFYFSDDTKNWTSSQRFCDSQDADLAQVE 
               
               
                 995 
                   sapiens ) 
                 SaQELNFLLRYKGPSDHWIGLSREQGQPWKWINGTEWTaQFPIL 
               
               
                   
                 CLEC2D 
                 GAGECAYLNDKGASSARCYTERKWICSKSDIHVHHHHHHHH 
               
               
                   
                 construct 90 
                   
               
               
                   
               
               
                 SEQ ID 
                 Human ( Homo   
                 MSFVSLLLVGILFHATQAQAACPESWIGFQRKCFYFSDDaKaWTSSQRFC 
               
               
                 996 
                   sapiens ) 
                 DSQDADLAQVESFQELNFLLRYKGPSDHWIGLSREQGQPWKWI 
               
               
                   
                 CLEC2D 
                 NGTEWTRQFPILGAGECAYLNDKGASSARCYTERKWICSKSDIH 
               
               
                   
                 construct 91 
                 VHHHHHHHH 
               
               
                   
               
               
                 SEQ ID 
                 Human ( Homo   
                 QAACPESWIGFQRKCFYFSDDaKaWTSSQRFCDSQDADLAQVES 
               
               
                 997 
                   sapiens ) 
                 FQELNFLLRYKGPSDHWIGLSREQGQPWKWINGTEWTRQFPILG 
               
               
                   
                 CLEC2D 
                 AGECAYLNDKGASSARCYTERKWICSKSDIHVHHHHHHHH 
               
               
                   
                 construct 92 
                   
               
               
                   
               
               
                 SEQ ID 
                 Human ( Homo   
                 MSFVSLLLVGILFHATQAQAACPESWIGFQRKCFYFSDDaKNWTSSQRFC 
               
               
                 998 
                   sapiens ) 
                 DSQDADLAQVESFQELNFLLRYKGPSDHWIGLSREQGQPWKWI 
               
               
                   
                 CLEC2D 
                 NGTEWTRQFPILGAGECAYLNDKGASSARCaTaRKWICSKSDIH 
               
               
                   
                 construct 93 
                 VHHHHHHHH 
               
               
                   
               
               
                 SEQ ID 
                 Human ( Homo   
                 QAACPESWIGFQRKCFYFSDDaKNWTSSQRFCDSQDADLAQVE 
               
               
                 999 
                   sapiens ) 
                 SFQELNFLLRYKGPSDHWIGLSREQGQPWKWINGTEWTRQFPIL 
               
               
                   
                 CLEC2D 
                 GAGECAYLNDKGASSARCaTaRKWICSKSDIHVHHHHHHHH 
               
               
                   
                 construct 94 
                   
               
               
                   
               
               
                 SEQ ID 
                 Human ( Homo   
                 MSFVSLLLVGILFHATQAQAACPESWIGFQRKCFYFSDDTaNWTSSQaFC 
               
               
                 1000 
                   sapiens ) 
                 DSQDADLAQVESFQELNFLLRYKGPSDHWIGLSREQGQPWKWI 
               
               
                   
                 CLEC2D 
                 NGTEWTRQFPILGAGECAYLNDKGASSARCYTaRKWICSKSDIH 
               
               
                   
                 construct 95 
                 VHHHHHHHH 
               
               
                   
               
               
                 SEQ ID 
                 Human ( Homo   
                 QAACPESWIGFQRKCFYFSDDTaNWTSSQaFCDSQDADLAQVES 
               
               
                 1001 
                   sapiens ) 
                 FQELNFLLRYKGPSDHWIGLSREQGQPWKWINGTEWTRQFPILG 
               
               
                   
                 CLEC2D 
                 AGECAYLNDKGASSARCYTaRKWICSKSDIHVHHHHHHHH 
               
               
                   
                 construct 96 
                   
               
               
                   
               
               
                 SEQ ID 
                 Human ( Homo   
                 MSFVSLLLVGILFHATQAQAACPESWIGFQRKCFYFSDDTKNWTSSQRFC 
               
               
                 1002 
                   sapiens ) 
                 DSQDADLAQVESFQELNFLLRYKGPSDHWIGLSREQGQPWKWI 
               
               
                   
                 CLEC2D 
                 NGTEWTRQFPILGAGECAYLNDKGASSAaCaTEaKWICSKSDIHV 
               
               
                   
                 construct 97 
                 HHHHHHHH 
               
               
                   
               
               
                 SEQ ID 
                 Human ( Homo   
                 QAACPESWIGFQRKCFYFSDDTKNWTSSQRFCDSQDADLAQVE 
               
               
                 1003 
                   sapiens ) 
                 SFQELNFLLRYKGPSDHWIGLSREQGQPWKWINGTEWTRQFPIL 
               
               
                   
                 CLEC2D 
                 GAGECAYLNDKGASSAaCaTEaKWICSKSDIHVHHHHHHHH 
               
               
                   
                 construct 98 
               
               
                   
               
            
           
         
       
     
     Antibodies 
     In one embodiment, the term “antibody” refers to an immunoglobulin, which may be derived from natural sources or synthetically produced, in whole or in part. The terms “antibody” and “immunoglobulin” are used synonymously throughout the specification unless otherwise stated. 
     In one embodiment, the term “antibody” includes both polyclonal and monoclonal antibody preparations and also includes the following: chimeric antibody molecules, F(ab′)2 and F(ab) fragments, Fv molecules, single chain Fv molecules (ScFv), dimeric and trimeric antibody fragments, bispecific antibody, minibodies, humanized monoclonal antibody molecules, human antibodies, fusion proteins comprising Fc region of antibody and any functional fragments arising out of these molecules, where derivative molecules retain immunological functionality of the parent antibody molecule. The antibody according to this disclosure is a human antibody, humanized antibody, chimeric antibody, or further genetically engineered antibody as long as the characteristic properties according to this disclosure are retained. 
     “Native antibodies and immunoglobulins” are usually heterotetrameric glycoproteins of about 150,000 daltons, composed of two identical light (L) chains and two identical heavy (H) chains. Each light chain is linked to a heavy chain by one covalent disulfide bond, while the number of disulfide linkages varies between the heavy chains of different immunoglobulin isotypes. Each heavy and light chain also has regularly spaced intrachain disulfide bridges. Each heavy chain has at one end a variable domain (VH) followed by a number of constant domains. Each light chain has a variable domain at one end (VL) and a constant domain at its other end; the constant domain of the light chain is aligned with the first constant domain of the heavy chain, and the light chain variable domain is aligned with the variable domain of the heavy chain. Particular amino acid residues are believed to form an interface between the light- and heavy-chain variable domains (Clothia et al., J. Mol. Biol. 186:651 (1985); Novotny and Haber, Proc. Natl. Acad. Sci. U.S.A. 82:4592 (1985)). 
     The term “antigen-binding site,” or “binding portion” refers to the part of the immunoglobulin molecule that participates in antigen binding. The antigen binding site is formed by amino acid residues of the N-terminal variable (“V”) regions of the heavy (“H”) and light (“L”) chains. Three highly divergent stretches within the V regions of the heavy and light chains, referred to as “hypervariable regions,” are interposed between more conserved flanking stretches known as “framework regions,” or “FRs”. Thus, the term “FR” refers to amino acid sequences which are naturally found between, and adjacent to, hypervariable regions in immunoglobulins. In an antibody molecule, the three hypervariable regions of a light chain and the three hypervariable regions of a heavy chain are disposed relative to each other in three dimensional space to form an antigen-binding surface. The antigen-binding surface is complementary to the three-dimensional surface of a bound antigen, and the three hypervariable regions of each of the heavy and light chains are referred to as “complementarity-determining regions,” or “CDRs.” 
     The term “variable” refers to the fact that certain portions of the variable domains differ extensively in sequence among antibodies and are used in the binding and specificity of each particular antibody for its particular antigen. However, the variability is not evenly distributed throughout the variable domains of antibodies. It is concentrated in three segments called complementarity-determining regions (CDRs) or hypervariable regions both in the light-chain and the heavy-chain variable domains. The more highly conserved portions of variable domains are called the framework (FR). The variable domains of native heavy and light chains each comprise four FR regions, largely adopting a β-sheet configuration, connected by three CDRs, which form loops connecting, and in some cases forming part of, the β-sheet structure. The CDRs in each chain are held together in close proximity by the FR regions and, with the CDRs from the other chain, contribute to the formation of the antigen-binding site of antibodies (see Kabat et al., Sequences of Proteins of Immunological Interest, Fifth Edition, National Institute of Health, Bethesda, Md. (1991)). The constant domains are not involved directly in binding an antibody to an antigen, but exhibit various effector functions, such as participation of the antibody in antibody-dependent cellular toxicity. 
     “Antibody fragments” comprise a portion of a full length antibody, preferably the variable domain thereof, or at least the antigen binding site thereof scFv antibodies are, e.g., described in Huston, J. S., Methods in Enzymol. 203 (1991) 46-88. In one embodiment, “antibody fragment” is a portion of a whole antibody which retains the ability to exhibit antigen binding activity. In addition, antibody fragments comprise single chain polypeptides having the characteristics of a VH domain, namely being able to assemble together with a VL domain, or of a VL domain binding to the respective antigen being able to assemble together with a VH domain to a functional antigen binding site and thereby providing the properties of an antibody according to this disclosure. 
     Papain digestion of antibodies produces two identical antigen-binding fragments, called “Fab” fragments, each with a single antigen-binding site, and a residual “Fc” fragment, whose name reflects its ability to crystallize readily. Pepsin treatment yields an F(ab′)2 fragment that has two antigen-combining sites and is still capable of cross-linking antigen. 
     “Fv” is the minimum antibody fragment which contains a complete antigen-recognition and binding site. This region consists of a dimer of one heavy- and one light-chain variable domain in tight, non-covalent association. It is in this configuration that the three CDRs of each variable domain interact to define an antigen-binding site on the surface of the VH-VL dimer. Collectively, the six CDRs confer antigen-binding specificity to the antibody. However, even a single variable domain (or half of an Fv comprising only three CDRs specific for an antigen) has the ability to recognize and bind antigen, although at a lower affinity than the entire binding site. 
     A single chain Fv (“scFv”) polypeptide molecule is a covalently linked VH:VL heterodimer, which can be expressed from a gene fusion including VH- and VL-encoding genes linked by a peptide-encoding linker. A number of methods have been described to discern chemical structures for converting the naturally aggregated, but chemically separated, light and heavy polypeptide chains from an antibody V region into an scFv molecule, which will fold into a three dimensional structure substantially similar to the structure of an antigen-binding site. See, e.g., U.S. Pat. Nos. 5,091,513; 5,132,405; and 4,946,778. 
     The Fab fragment also contains the constant domain of the light chain and the first constant domain (CH1) of the heavy chain. Fab′ fragments differ from Fab fragments by the addition of a few residues at the carboxy terminus of the heavy chain CH1 domain including one or more cysteines from the antibody hinge region. Fab′-SH is the designation herein for Fab′ in which the cysteine residue(s) of the constant domains bear a free thiol group. F(ab′)2 antibody fragments originally were produced as pairs of Fab′ fragments which have hinge cysteines between them. Other chemical couplings of antibody fragments are also known. 
     The “light chains” of antibodies (immunoglobulins) from any vertebrate species can be assigned to one of two clearly distinct types, called kappa (k) and lambda (l), based on the amino acid sequences of their constant domains. 
     As used herein, the terms “immunological binding” and “immunological binding properties” refer to the non-covalent interactions of the type which occur between an immunoglobulin molecule and an antigen for which the immunoglobulin is specific. The strength, or affinity of immunological binding interactions can be expressed in terms of the dissociation constant (Kd) of the interaction, wherein a smaller Kd represents a greater affinity. Immunological binding properties of selected polypeptides can be quantified using methods well known in the art. One such method entails measuring the rates of antigen-binding site/antigen complex formation and dissociation, wherein those rates depend on the concentrations of the complex partners, the affinity of the interaction, and geometric parameters that equally influence the rate in both directions. Thus, both the “on rate constant” (Kon) and the “off rate constant” (Koff) can be determined by calculation of the concentrations and the actual rates of association and dissociation. The ratio of Koff/Kon enables the cancellation of all parameters not related to affinity, and is equal to the dissociation constant Kd. In some embodiments, an antibody of the present disclosure binds to CLEC2D at a Kd≤10 μM, preferably ≤1 μM, more preferably ≤100 nM, for example, ≤90 nM, ≤80 nM, ≤70 nM, ≤60 nM, ≤50 nM, ≤40 nM, ≤30 nM, ≤20 nM, ≤10 nM, ≤5 nM, or ≤1 nM, as measured by assays such as radioligand binding assays or similar assays known to those skilled in the art. In some embodiment, the binding affinity of the antibody of this disclosure is within the range of 10 −5 M to 10 −12  M. For example, the binding affinity of the antibody of this disclosure is from 10 −6 M to 10 −12  M, from 10 −7 M to 10 −12  M, from 10 −8 M to 10 −12  M, from 10 −9 M to 10 −12  M, from 10 −5  M to 10 −11  M, from 10 −6 M to 10 −11 M, from 10 −7  M to 10 −11  M, from 10 −8 M to 10 −11 M, from 10 −9 M to 10 −11  M, from 10 −10  M to 10 −11 M, from 10 −5 M to 10 −10  M, from 10 −6 M to 10 −10 , from 10 −7  M to 10 −10  M, from 10 −8 M to 10 −10 , from 10 −9  M to 10 −10  M, from 10 −5  M to 10 −9  M, from 10 −6  M to 10 −9  M, from 10 −7 M to 10 −9  M, from 10 −8  M to 10 −9 M, from 10 −5  M to 10 −8 M, from 10 −6  M to 10 −8 M, from 10 −7 M to 10 −8 M, from 10 −5  M to 10 −7  M, from 10 −6 M to 10 −7 M or from 10 −5  M to 10 −6 M. 
     The present disclosure also features antibodies that have a specified percentage identity or similarity to the amino acid or nucleotide sequences of the CLEC2D antibodies described herein. For example, the antibodies may have at least 30%, 40%, 50%, 60%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or higher identity when compared a specified region or the full length of any one of the CLEC2D antibodies described herein. Preferably, the antibodies may have at least 60%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or higher identity when compared a specified region or the full length of any one of the CLEC2D antibodies described herein. More preferably, the antibodies may have at least 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or higher identity when compared a specified region or the full length of any one of the CLEC2D antibodies described herein. Even more preferably, the antibodies may have at least 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or higher identity when compared a specified region or the full length of any one of the CLEC2D antibodies described herein. Sequence identity or similarity to the nucleic acids and proteins of the present disclosure can be determined by sequence comparison and/or alignment by methods known in the art. For example, sequence comparison algorithms (i.e., BLAST or BLAST 2.0), manual alignment or visual inspection can be utilized to determine percent sequence identity or similarity for the nucleic acids and proteins of the present disclosure. 
     As to amino acid sequences, one of skill in the art will readily recognize that individual substitutions, deletions or additions to a nucleic acid, peptide, polypeptide, or protein sequence which alters, adds, deletes, or substitutes a single amino acid or a small percentage of amino acids in the encoded sequence is collectively referred to herein as a “conservatively modified variant”. In some embodiments, the alteration results in the substitution of an amino acid with a chemically similar amino acid. Conservative substitution tables providing functionally similar amino acids are well known in the art. 
     Depending on the amino acid sequence of the constant domain of their heavy chains, immunoglobulins can be assigned to different classes. There are five major classes of immunoglobulins: IgA, IgD, IgE, IgG, and IgM, and several of these can be further divided into subclasses (isotypes), e.g., IgG1, IgG2, IgG3, IgG4, IgA1, and IgA2. The heavy-chain constant domains that correspond to the different classes of immunoglobulins are called α, ∂, ε, γ, and μ, respectively. The subunit structures and three-dimensional configurations of different classes of immunoglobulins are well known. 
     In one embodiment, a humanized antibody may be used in the compositions and methods provided herein. In some embodiments, the term “humanized antibody” or “humanized version of an antibody” refers to antibodies in which the framework or “complementarity determining regions” (CDR) have been modified to comprise the CDR of an immunoglobulin of different specificity as compared to that of the parent immunoglobulin. In other embodiments, the CDRs of the VH and VL are grafted into the framework region of human antibody to prepare the “humanized antibody.” See e.g., Riechmann, L., et al, Nature 332 (1988) 323-327; and Neuberger, M. S., et al, Nature 314 (1985) 268-270. The heavy and light chain variable framework regions can be derived from the same or different human antibody sequences. The human antibody sequences can be the sequences of naturally occurring human antibodies. Human heavy and light chain variable framework regions are listed e.g., in Lefranc, M.-P., Current Protocols in Immunology (2000)—Appendix IP A.1P.1-A.1P.37 and are accessible via IMGT, the international ImMunoGeneTics information System® (http://imgt.cines.fr) or via http://vbase.mrc-cpe.cam.ac.uk. Optionally the framework region can be modified by further mutations. Particularly preferred CDRs correspond to those representing sequences recognizing the antigens noted above for chimeric antibodies. The term “humanized antibody” as used herein also comprises such antibodies which are modified in the constant region to generate the properties according to this disclosure, especially in regard to Clq binding and/or FcR binding, e.g., by “class switching” i.e., change or mutation of Fc parts (e.g., from IgG1 to IgG4 and/or IgG1/IgG4 mutation). The term “human antibody”, as used herein, is intended to include antibodies having variable and constant regions derived from human germ line immunoglobulin sequences. Human antibodies are well-known in the state of the art (van Dijk, M. A., and van de Winkel, J. G., Curr. Opin. Chem. Biol. 5 (2001) 368-374). Human antibodies can also be produced in transgenic animals (e.g., mice) that are capable, upon immunization, of producing a full repertoire or a selection of human antibodies in the absence of endogenous immunoglobulin production. Transfer of the human germ-line immunoglobulin gene array in such germ-line mutant mice will result in the production of human antibodies upon antigen challenge (see, e.g., Jakobovits, A., et al, Proc. Natl. Acad. Sci. USA 90 (1993) 2551-2555; Jakobovits, A., et al, Nature 362 (1993) 255-258; Brueggemann, M. D., et al., Year Immunol. 7 (1993) 33-40). Human antibodies can also be produced in phage display libraries (Hoogenboom, H. R., and Winter, G., J. Mol. Biol. 227 (1992) 381-388; Marks, J. D., et al, J. Mol. Biol. 222 (1991) 581-597). The techniques of Cole, A., et al. and Boerner, P., et al. are also available for the preparation of human monoclonal antibodies (Cole, A., et al., Monoclonal Antibodies and Cancer Therapy, Liss, A. L., p. 77 (1985); and Boerner, P., et al, J. Immunol. 147 (1991) 86-95). As already mentioned for humanized antibodies according to this disclosure the term “human antibody” as used herein also comprises such antibodies which are modified in the constant region to generate the properties according to this disclosure. 
     In one embodiment, the term “monoclonal antibody” refers to an antibody composition having a homogeneous antibody population. The antibody is not limited to the species or source of the antibody or by the manner in which it is made. In another embodiment, the term encompasses whole immunoglobulins as well as fragments such as Fab, F(ab′)2, Fv, and other fragments, as well as chimeric and humanized homogeneous antibody populations that exhibit immunological binding properties of the parent monoclonal antibody molecule. In another embodiment, the terms “monoclonal antibody” or “monoclonal antibody composition” as used herein refer to a preparation of antibody molecules of a single amino acid composition. In another embodiment, the terms Fab or ScFv are used as antibody fragments with specific mention. 
     In some embodiments, a chimeric antibody may be used in the compositions and methods provided herein. In one embodiment, the term “chimeric antibody” refers to a monoclonal antibody comprising a variable region, i.e., binding region, from one species (e.g., a mouse or rat) and at least a portion of a constant region derived from a different source or species (e.g., human), usually prepared by recombinant DNA techniques. Chimeric antibodies comprising a mouse variable region and a human constant region are especially preferred. Such chimeric antibodies are the product of expressed immunoglobulin genes comprising DNA segments encoding immunoglobulin variable regions from one species and DNA segments encoding immunoglobulin constant regions for a different species. Other forms of “chimeric antibodies” encompassed by the present disclosure are those in which the class or subclass has been modified or changed from that of the original antibody. Such “chimeric” antibodies are also referred to as “class-switched antibodies.” Methods for producing chimeric antibodies involve conventional recombinant DNA and gene transfection techniques now well known in the art. See, e.g., Morrison, S. L., et al, Proc. Natl. Acad Sci. USA 81 (1984) 6851-6855; U.S. Pat. Nos. 5,202,238 and 5,204,244. 
     In one embodiment, “antibody display library” refers to a platform(s) expressing antibodies on the surface of a cell or cell-free suited for a screening methodology against target antigens. Herein, phage display library and yeast display library are used with accurate specification unless indicated otherwise. 
     In one embodiment, the term “naïve library” refers to a collection of nucleic acid sequences encoding a naturally occurring VH repertoire from a non-immunized source. 
     In one embodiment, the term “VH” refers to the single heavy chain variable domain of antibody of the type that can be found in mammals which are naturally devoid of light chains or parts of the same; Naive VH can be understood accordingly. 
     In one embodiment, the term “VL” refers to single light chain variable domain of the antibody; they are found in two types based on the constant domain sequence. Vk (with kappa constant region) and V1 (lambda constant region) are understood accordingly. 
     In one embodiment, the term “CDR” refers to complementary determining region of the antibody structure. 
     In one embodiment, the term “repertoire,” means a collection, indicating genetic diversity. 
     In one embodiment, the term “framework region” is used herein to refer to the nucleic acid sequence regions of an antibody molecule that encode the structural elements of the molecule. 
     In another embodiment, the term “vector” refers to a DNA related to a cloning or expression system to accommodate antibody genes in specific designated restriction sites. Phagemid vectors (applicable to phage display systems) or yeast vectors (applicable to yeast display systems) are understood accordingly or mammalian expression vectors (applicable to mammalian expression systems). 
     The disclosure provides antibodies and antibody fragments that bind to a CLEC2D antigen of the disclosure. 
     The disclosure provides VH and VL domains of antibodies or antibody fragments that bind to a CLEC2D antigen or an epitope of CLEC2D as described in the disclosure. 
     The disclosure provides sequences of CDR1, CDR2 and CDR3 of the VH domain and CDR1, CDR2 and CD3 of the VL domain of antibodies that bind to a CLEC2D antigen or an epitope of CLEC2D as described in the disclosure. 
     Any combinations of VH and VL sequences of the disclosure are considered within the scope of this disclosure. Any combinations of the CDR1, CDR2 and CDR3 sequences of the VH domains, or the CDR1, CDR2 and CD3 sequences of the VL domains are considered within the scope of this disclosure. 
     Those skilled in the art will recognize that it is possible to determine, without undue experimentation, if a monoclonal antibody has the same specificity as a monoclonal antibody of the disclosure by ascertaining whether the former prevents the latter from binding to CLEC2D. If the monoclonal antibody being tested competes with the monoclonal antibody of the disclosure, as shown by a decrease in binding by the monoclonal antibody of the disclosure, then it is likely that the two monoclonal antibodies bind to the same, or to a closely related, epitope. 
     Another way to determine whether a monoclonal antibody has the specificity of a monoclonal antibody of the disclosure is to pre-incubate the monoclonal antibody of the disclosure with the CLEC2D protein, with which it is normally reactive, and then add the monoclonal antibody being tested to determine if the monoclonal antibody being tested is inhibited in its ability to bind CLEC2D. If the monoclonal antibody being tested is inhibited then, in all likelihood, it has the same, or functionally equivalent, epitopic specificity as the monoclonal antibody of the disclosure. Screening of monoclonal antibodies of the disclosure can be also carried out by utilizing CLEC2D and determining whether the test monoclonal antibody is able to neutralize CLEC2D. 
     Various procedures known within the art may be used for the production of polyclonal or monoclonal antibodies directed against a protein of the disclosure, or against derivatives, fragments, analogs homologs or orthologs thereof. (See, for example, Antibodies: A Laboratory Manual, Harlow E, and Lane D, 1988, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y., incorporated herein by reference). 
     Antibodies can be purified by well-known techniques, such as affinity chromatography using protein A or protein G, which provide primarily the IgG fraction of immune serum. Subsequently, or alternatively, the specific antigen which is the target of the immunoglobulin sought, or an epitope thereof, may be immobilized on a column to purify the immune specific antibody by immunoaffinity chromatography. Purification of immunoglobulins is discussed, for example, by D. Wilkinson (The Scientist, published by The Scientist, Inc., Philadelphia Pa., Vol. 14, No. 8 (Apr. 17, 2000), pp. 25-28). 
     Monoclonal antibodies can be prepared using hybridoma methods, such as those described by Kohler and Milstein, Nature, 256:495 (1975). In a hybridoma method, a mouse, hamster, or other appropriate host animal, is typically immunized with an immunizing agent to elicit lymphocytes that produce or are capable of producing antibodies that will specifically bind to the immunizing agent. Alternatively, the lymphocytes can be immunized in vitro. 
     The immunizing agent will typically include the protein antigen, a fragment thereof or a fusion protein thereof. Generally, either peripheral blood lymphocytes are used if cells of human origin are desired, or spleen cells or lymph node cells are used if non-human mammalian sources are desired. The lymphocytes are then fused with an immortalized cell line using a suitable fusing agent, such as polyethylene glycol, to form a hybridoma cell (Goding, Monoclonal Antibodies: Principles and Practice, Academic Press, (1986) pp. 59-103). Immortalized cell lines are usually transformed mammalian cells, particularly myeloma cells of rodent, bovine and human origin. Usually, rat or mouse myeloma cell lines are employed. The hybridoma cells can be cultured in a suitable culture medium that preferably contains one or more substances that inhibit the growth or survival of the unfused, immortalized cells. For example, if the parental cells lack the enzyme hypoxanthine guanine phosphoribosyl transferase (HGPRT or HPRT), the culture medium for the hybridomas typically will include hypoxanthine, aminopterin, and thymidine (“HAT medium”), which substances prevent the growth of HGPRT-deficient cells. 
     Preferred immortalized cell lines are those that fuse efficiently, support stable high level expression of antibody by the selected antibody-producing cells, and are sensitive to a medium such as HAT medium. More preferred immortalized cell lines are murine myeloma lines, which can be obtained, for instance, from the Salk Institute Cell Distribution Center, San Diego, Calif. and the American Type Culture Collection, Manassas, Va. Human myeloma and mouse-human heteromyeloma cell lines also have been described for the production of human monoclonal antibodies. (See Kozbor, J. Immunol., 133:3001 (1984); Brodeur et al., Monoclonal Antibody Production Techniques and Applications, Marcel Dekker, Inc., New York, (1987) pp. 51-63)). 
     The culture medium in which the hybridoma cells are cultured can then be assayed for the presence of monoclonal antibodies directed against the antigen. Preferably, the binding specificity of monoclonal antibodies produced by the hybridoma cells is determined by immunoprecipitation or by an in vitro binding assay, such as radioimmunoassay (MA) or enzyme-linked immunoabsorbent assay (ELISA). Such techniques and assays are known in the art. The binding affinity of the monoclonal antibody can, for example, be determined by the Scatchard analysis of Munson and Pollard, Anal. Biochem., 107:220 (1980). Moreover, in therapeutic applications of monoclonal antibodies, it is important to identify antibodies having a high degree of specificity and a high binding affinity for the target antigen. 
     After the desired hybridoma cells are identified, the clones can be subcloned by limiting dilution procedures and grown by standard methods. (See Goding, Monoclonal Antibodies: Principles and Practice, Academic Press, (1986) pp. 59-103). Suitable culture media for this purpose include, for example, Dulbecco&#39;s Modified Eagle&#39;s Medium and RPMI-1640 medium. Alternatively, the hybridoma cells can be grown in vivo as ascites in a mammal. 
     The monoclonal antibodies secreted by the subclones can be isolated or purified from the culture medium or ascites fluid by conventional immunoglobulin purification procedures such as, for example, protein A-Sepharose, hydroxylapatite chromatography, gel electrophoresis, dialysis, or affinity chromatography. 
     Monoclonal antibodies can also be made by recombinant DNA methods, such as those described in U.S. Pat. No. 4,816,567. DNA encoding the monoclonal antibodies of the disclosure can be readily isolated and sequenced using conventional procedures (e.g., by using oligonucleotide probes that are capable of binding specifically to genes encoding the heavy and light chains of murine antibodies). In some embodiments, the hybridoma cells of the disclosure serve as a source of such DNA. In some embodiments, antibody gene sequences are isolated and cloned using the methods of the disclosure (e.g., phage and yeast library display), and serve as the source of such DNA. Once isolated, the DNA can be placed into expression vectors, which are then transfected into host cells such as simian COS cells, Chinese hamster ovary (CHO) cells, or myeloma cells that do not otherwise produce immunoglobulin protein, to obtain the synthesis of monoclonal antibodies in the recombinant host cells. The DNA also can be modified, for example, by substituting the coding sequence for human heavy and light chain constant domains in place of the homologous murine sequences (see U.S. Pat. No. 4,816,567; Morrison, Nature 368, 812-13 (1994)) or by covalently joining to the immunoglobulin coding sequence all or part of the coding sequence for a non-immunoglobulin polypeptide. Such a non-immunoglobulin polypeptide can be substituted for the constant domains of an antibody of the disclosure, or can be substituted for the variable domains of one antigen-combining site of an antibody of the disclosure to create a chimeric bivalent antibody. 
     All cell lines suitable for the expression and purification of antibodies or antibody fragments are considered to be within the scope of the disclosure. In some embodiments, the cell line is a mammalian cell line. Cell lines can be isolated or derived from any source, including human, mouse and hamster. Suitable cell lines include, but are not limited to, Chinese Hamster Ovary (CHO) cells, HEK 293 cells, HEK293T cells, BHK21 cells, NSO cells, PER.C6 cells, B cells, HEK 293-6E cells, Sp2/0-Ag14 cells and DG44 cells. In some embodiments, the cell line is a hybridoma cell line. 
     The antibody can be expressed by a vector containing a DNA segment encoding the single chain antibody described herein. 
     These can include vectors, liposomes, naked DNA, adjuvant-assisted DNA, gene gun, catheters, etc. Vectors include chemical conjugates such as described in WO 93/64701, which has targeting moiety (e.g., a ligand to a cellular surface receptor), and a nucleic acid binding moiety (e.g., polylysine), viral vector (e.g., a DNA or RNA viral vector), fusion proteins such as described in PCT/US 95/02140 (WO 95/22618) which is a fusion protein containing a target moiety (e.g., an antibody specific for a target cell) and a nucleic acid binding moiety (e.g., a protamine), plasmids, phage, etc. The vectors can be chromosomal, non-chromosomal or synthetic. 
     Preferred vectors include viral vectors, fusion proteins and chemical conjugates. Retroviral vectors include moloney murine leukemia viruses. DNA viral vectors are preferred. These vectors include pox vectors such as orthopox or avipox vectors, herpesvirus vectors such as a herpes simplex I virus (HSV) vector (see Geller, A. I. et al., J. Neurochem, 64:487 (1995); Lim, F., et al., in DNA Cloning: Mammalian Systems, D. Glover, Ed. (Oxford Univ. Press, Oxford England) (1995); Geller, A. I. et al., Proc Natl. Acad. Sci.: U.S.A. 90:7603 (1993); Geller, A. I., et al., Proc Natl. Acad. Sci USA 87:1149 (1990), Adenovirus Vectors (see LeGal LaSalle et al., Science, 259:988 (1993); Davidson, et al., Nat. Genet 3:219 (1993); Yang, et al., J. Virol. 69:2004 (1995) and Adeno-associated Virus Vectors (see Kaplitt, M. G. et al., Nat. Genet. 8:148 (1994). 
     Pox viral vectors introduce the gene into the cells cytoplasm. Avipox virus vectors result in only a short term expression of the nucleic acid. Adenovirus vectors, adeno-associated virus vectors and herpes simplex virus (HSV) vectors are preferred for introducing the nucleic acid into neural cells. The adenovirus vector results in a shorter term expression (about 2 months) than adeno-associated virus (about 4 months), which in turn is shorter than HSV vectors. The particular vector chosen will depend upon the target cell and the condition being treated. The introduction can be by standard techniques, e.g., infection, transfection, transduction or transformation. Examples of modes of gene transfer include e.g., naked DNA, CaPO4 precipitation, DEAE dextran, electroporation, protoplast fusion, lipofection, cell microinjection, and viral vectors. 
     Exemplary VH amino acid sequences of CLEC2D antibodies of the disclosure are shown in Table 2 below. VH amino acid sequences having at least 50% identity, at least 55% identity, at least 60% identity, at least 65% identity, at least 70% identity, at least 75% identity, at least 80% identity, at least 85% identity, at least 90% identity, at least 91% identity, at least 92% identity, at least 93% identity, at least 94% identity, at least 95% identity, at least 96% identity, at least 97% identity, at least 98% identity, at least 99% identity, at least 99.5% identity, at least 99.8% identity, at least 99.9% identity or 100% identity to the sequences listed in Table 2 are considered within the scope of the disclosure. 
     
       
         
           
               
             
               
                 TABLE 2 
               
             
            
               
                   
               
               
                 VH Amino Acid Sequences 
               
            
           
           
               
               
            
               
                 SEQ ID 
                 VH Amino Acid Sequence 
               
               
                   
               
               
                 SEQ ID 1 
                 EVQLVQSGAEVKKPGASVKVSCKASGYTFTSYAMHWVRQAPGQRLEWMGWINAGNGNTKYSQKFQGRVTI 
               
               
                   
                 TRDTSASTAYMELSSLRSEDTAVYYCARGSLSRSGWYAGLFDYWGQGTLVTVSS 
               
               
                   
               
               
                 SEQ ID 2 
                 QITLKESGGGVVQPGRSLRLSCAASGFTFSSYSMNWVRQAPGKGLQWVAIISDDGSKSYYADSVQGRFTISRD 
               
               
                   
                 NSRNTVFLQMNSLRAEDTAMYYCARDRGTKWNQLNDVFDMWGQGTMVTVSS 
               
               
                   
               
               
                 SEQ ID 3 
                 EVQLVQSGAEVKKPGASVKVSCKASGYTFTSYYMHWVRQAPGQGLEWMGIINPSGGSTSYAQKFQGRVTMT 
               
               
                   
                 RDTSTSTVYMELSSLRSEDTAVYYCARGRGYSSSRLYYFDYWGQGTLVTVSS 
               
               
                   
               
               
                 SEQ ID 4 
                 QVTLKESGGGLVRPGGSLRLSCEASGFTFSDPYMDWVRQAPGKGLEWVGRITNKRTGYATTYAASVKDRFTIS 
               
               
                   
                 RDDSRKSVYLQMNSLKTEDTAVYYCATDVSGSFAAYGGQGTLVTVSS 
               
               
                   
               
               
                 SEQ ID 5 
                 EVQLVQSGGGVVQPGRSLRLSCAASGFTFSSYAMHWVRQAPGQRLEWMGWINAGNGNTKYSQKFQGRVTI 
               
               
                   
                 TRDTSASTAYMELSSLRSEDTAVYYCAGEGGAVAGTVYWGQGTLVTVSS 
               
               
                   
               
               
                 SEQ ID 6 
                 QVQLVQSGGGLVKPGGSLRLSCAASGFTFSNAWMSWVRQAPGKGLEWVGRIKSKTDGGTTDYAAPVKGRFT 
               
               
                   
                 ISRDDSKNTLYLQMNSLKTEDTAVYYCTIDEYFYWGQGTLVTVSS 
               
               
                   
               
               
                 SEQ ID 7 
                 QVQLQQWGAGLLKPSETLSLTCAVYGGSFSGYYWSWIRQPPGKGLEWIGEINHSGSTNYNPSLKSRVTISVDTS 
               
               
                   
                 KNQFSLKLSSVTAADTAVYYCARVNPGSYTREVSNFDYWGQGTLVTVSS 
               
               
                   
               
               
                 SEQ ID 8 
                 QVQLQQSGPELVKPSQTLTLICGISGDSVSSNSVTWNWVRQSPSRGLEWLGRTYYRSQWYYNYAVSVKSRITI 
               
               
                   
                 SPDTSKNQFSLQLNSVTPEDTAVYYCATRGHNYGVDYWGPGTTVTVSS 
               
               
                   
               
               
                 SEQ ID 9 
                 QVQLVQSGGGLVKPGGSLRLSCAASGFTFSNAWMSWVRQAPGKGLEWVCRIKSKTDGETTDYAAPVKGRFTI 
               
               
                   
                 SRDDSKNTLYLQMNSLKTEDTAVYHCTTGVGWSPFQYWGQGTLVTVSS 
               
               
                   
               
               
                 SEQ ID 10 
                 EVQLVQSGGGLVQPGRSLRLSCTASGFTFGDYAMSWFRQAPGKGLEWVGFIRSKAYGGTTEYAASVKGRFTIS 
               
               
                   
                 RDDSKSIAYLQMNSLKTEDTAVYYCTRDDKIAAAGFTYWYFDLWGRGTLVTVSS 
               
               
                   
               
               
                 SEQ ID 11 
                 QVQLVQSGAEVKKPGASVKVSCKASGYTFAAYYLHWVRQAPGQGLEWMGRISPGNGVTSYAQKFQGRVTM 
               
               
                   
                 TGDTSINTVYMQLNNLISGDTAVYYCAREAADDPFDHWGQGALVTVSS 
               
               
                   
               
               
                 SEQ ID 12 
                 EVQLVQSGGGVVQPGRSLTLSCAASGFTFSSHLMHWVRQAPGKGLEWVAVISYDGTSKYYGDSVKGRFTISRD 
               
               
                   
                 NSKNTLYLQMNSLRAEDTAIYYCAKADYKYDWGQGTLVTVSS 
               
               
                   
               
               
                 SEQ ID 13 
                 EVQLVQSGGGLVKPGGSLRLSCTASGFTFGDYAMSWVRQAPGKGLEWVGFIRSKAYGGTTEYAASVKGRFTIS 
               
               
                   
                 RDDSKSIAYLQMNSLKTEDTAVYYCTTHRRPIYDILTGFDYWGQGTLVTVSS 
               
               
                   
               
               
                 SEQ ID 14 
                 QLQLQESGGGLVQPGRSLRLSCTASGFTFGDYAMSWVRQAPGKGLEWVGFIRSKAYGGTTEYAASVKGRFTIS 
               
               
                   
                 RDDSKSIAYLQMNSLKTEDTAVYYCTREDTMVRGVIPWGQGTLVTVSS 
               
               
                   
               
               
                 SEQ ID 15 
                 QLQLQESGSGLVKPSQTLSLTCAVSGGSISSGGYSWSWIRQPPGKGLEWIGYIYHSGSTYYNPSLKSRVTISVDRS 
               
               
                   
                 KNQFSLKLSSVTAADTAVYYCARDRRYYDSSGYYPAYYFDYWGQGTLVTVSS 
               
               
                   
               
               
                 SEQ ID 16 
                 EVQLVQSGGGLVKPGGSLRLSCAASGFTFSSYSMNWVRQAPGKGLEWVSYISSSGSYTNYADSVKGRFTISRD 
               
               
                   
                 NAKNSLYLQINSLRAEDTAIYYCARDGGYDSSGFHFDYWGQGTLVTVSS 
               
               
                   
               
               
                 SEQ ID 17 
                 QVQLQQSGPGLVKPSQTLSLTCAISGDSVSNNRAAWNWIRQSPSRGLEWLGRTYYRSKWYNEYAVSVKSRITI 
               
               
                   
                 NPDTSKNQFSLQLNSMTPEDSAVYYCAILPSSGYLQDHHYYGMDVWGQGTTVTVSS 
               
               
                   
               
               
                 SEQ ID 18 
                 EVQLVQSGAEVKKPGASVKVSCKASGYTFTSYGISWVRQAPGQGLEWMGWISAYNGNTNYAQKLQGRVTM 
               
               
                   
                 TTDTSTSTAYMELSSLRSEDTAVYYCARAAVGDGYSYGRLDWGQGTLVTVSS 
               
               
                   
               
               
                 SEQ ID 19 
                 EVQLVQSGAEVKKPGESLKISCKGSGYSFTSYWIGWVRQMPGKGLEWMGIIYPGDSDTRYSPSFQGQVTISAD 
               
               
                   
                 KSISTAYLQWSSLKASDTAMYYCARLPSYYYDSSGYFTWYFDLWGRGTLVTVSS 
               
               
                   
               
               
                 SEQ ID 20 
                 EVQLVQSGAEVKKPGASVKVSCKASGYTFTSYGISWVRQAPGQGLEWMGWIIPIFGIANYAQKFQGRVTITAD 
               
               
                   
                 KSTSTAYMELSSLRSEDTAVYYCARELYNYGSKDYFDYWGQGTLVTVSS 
               
               
                   
               
               
                 SEQ ID 21 
                 EVQLVQSGAEVKKPGESLKISCKGSGYSFTSYWIGWVRQMPGKGLEWMGIIYPGDSDTRYSPSFQGQVTISAD 
               
               
                   
                 KSISTAYLQWSSLKASDTAMYYCARGGTWDTAMVTGFDYWGQGTLVTVSS 
               
               
                   
               
               
                 SEQ ID 22 
                 EVQLVQSGAEVKKPGESLKISCKGSGYSFTSYWIAWVRQMPGKGLEWMGVIYPGDSDTRYSPSFQGQVTISAD 
               
               
                   
                 KSINTAYLQWSSLKASDTAMYYCARPHYDILTGSRAPFDYWGQGTLVTVSS 
               
               
                   
               
               
                 SEQ ID 23 
                 QVQLQQWGAGLLKPSETLSLTCAVYGGSFSGYYWSWIRQPPGKGLEWIGEINHSGSTNYNPSLKSRVTISVDTS 
               
               
                   
                 KNQFSLKLSSVTAADTAVYYCARARVESKDGYFDYWGQGTLVTVSS 
               
               
                   
               
               
                 SEQ ID 24 
                 EVQLVESGGGVVQPGRSLRLSCAASGFTFTDAWMNWVRQAPGKGLEWIGRVKNKADGETTDYAAPVKGRIT 
               
               
                   
                 ISRDDAKNTLYVQMNSLKTEDTAVYYCTADLRLSTWDAYDFWGQGTMVTVSS 
               
               
                   
               
               
                 SEQ ID 25 
                 QITLKESGGGLVQPGGSLRLSCTVSGFTFSNNWMTWVRQTPGKGLEWVANIKQDGTEKHYVDSVKGRFTISR 
               
               
                   
                 DNAENSLYLQMNSLRGEDTAVYYCARNSQRSFDYWGQGTLVTVSS 
               
               
                   
               
               
                 SEQ ID 26 
                 QVTLKESGGGVVQPGRSLRLSCAASGFTFSSYGMHWVRQAPGKGLEWVAVISYDGSNKYYADSVKGRFTISR 
               
               
                   
                 DNSKNTLYLQMNSLRAEDTAVYYCAKDLGDPRGGILNYWGQGTLVTVSS 
               
               
                   
               
               
                 SEQ ID 27 
                 EVQLVESGGGVVQPGRSLRLSCAASGFTFSSYAMHWVRQAPGKGLEWVAVISYDGSNKYYADSVKGRFTISRD 
               
               
                   
                 NSKNTLYLQMNSLRAEDTAVYYCARSSPWGELSLYQGAFDIWGQGTMVTVSS 
               
               
                   
               
               
                 SEQ ID 28 
                 QITLKESGGGLVQPGRSLRLSCAASGFTFDDYAMHWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRFTISRD 
               
               
                   
                 NSKNTLYLQMNSLRAEDTAVYYCAKDNDFWSGKVFDYWGQGTLVTVSS 
               
               
                   
               
               
                 SEQ ID 29 
                 EVQLVQSGGGLVQPGGSLRLSCAASGFTFSSYSMNWVRQAPGKGLEWVSYISSTSSTIYYADSVKGRFTISRDN 
               
               
                   
                 SKNMLFLQMNSLRAEDTAVYYCAKEGGSGWRHYFDYWGQGTLVTVSS 
               
               
                   
               
               
                 SEQ ID 30 
                 QVTLKESGGGVVQPGRSLRLSCAASGFTFSSYAMHWVRQAPGKGLEWVAVISYDGSNKYYADSVKGRFTISRD 
               
               
                   
                 NSKNTLYLQMNSLRAEDTAVYYCARDYCSSTSCQNWFDPWGQGTLVTVSS 
               
               
                   
               
               
                 SEQ ID 31 
                 QVQLVQSGGGLVQPGGSLRLSCAASGFTFSNYVMSWVRQAPGKGLEWVSAISGIGDTTYYADSVKGRFTISRD 
               
               
                   
                 NAKNTLYLQMNSLRAEDTAVYYCARGRVAGDAFDIWGQGTMVTVSS 
               
               
                   
               
               
                 SEQ ID 32 
                 QLQLQESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRFTISRD 
               
               
                   
                 NSKNTLYLQMNSLRAEDTAVYYCAKDQGAAAGTLGYFDYWGQGTLVTVSS 
               
               
                   
               
               
                 SEQ ID 33 
                 QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYDINWVRQATGQGLEWMGWMNPNSGNTGYAQKFQGRVT 
               
               
                   
                 MTRNTSISTAYMELSSLRSEDTAVYYCTRGIYDSSGSSNPFDSWGQGTLVTVSS 
               
               
                   
               
               
                 SEQ ID 34 
                 EVQLVQSGAEVKKPGASVKISCEASGYTFTDYAIHWVRQAPGQRLEWMGWINAGDGGTKSSREFQGRVTITR 
               
               
                   
                 DTSATTAYMEVSSLRSEDTAVYYCARGYCSGGSCPGTDFDYWGQGTLVTVSS 
               
               
                   
               
               
                 SEQ ID 35 
                 QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYYMHWVRQAPGQGLEWMGIINPSGGSTSYAQKFQGRVTM 
               
               
                   
                 TRDTSTSTVYMELSSLRSEDTAVYYCARDGVGGRDGYNFDYWGQGTLVTVSS 
               
               
                   
               
               
                 SEQ ID 36 
                 EVQLVQSGGGLVQPGGSLRLSCAASGFTVSSNYMSWVRQAPGKGLEWVSVIYSGGSTYYADSVKGRFTISRDN 
               
               
                   
                 SKNTLYLQMNSLRAEDTAVYYCARAPLAADGYFDYWGQGTLVTVSS 
               
               
                   
               
               
                 SEQ ID 37 
                 EVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAISWVRQAPGQGLEWMGGIIPIFGTANYAQKFQGRVTITAD 
               
               
                   
                 ESTSTAYMELSSLRSEDTAVYYCARARGLQYLIWYFDLWGRGTLVTVSS 
               
               
                   
               
               
                 SEQ ID 38 
                 QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYYMHWVRQAPGQGLEWMGIINPSGGSTSYAQKFQGRVTM 
               
               
                   
                 TRDTSTSTVYMELSSLRSEDTAVYYCASPGMVRGVITAPLDYWGQGTLVTVSS 
               
               
                   
               
               
                 SEQ ID 39 
                 EVQLVQSGGGLVKPGGSLRLSCAASGFTFSSYAISWVRQAPGQGLEWMGGIIPMYGTANYAQKFQGRVTITA 
               
               
                   
                 DESTSTAYMELSSLRSEDTALYYCAREAKWGMYYFDYWGQGTLVTVSS 
               
               
                   
               
               
                 SEQ ID 40 
                 EVQLVESGGGVVQPGRSLRLSCAASGFTFSSYAIHWVRQAPGKGLEWVAIISDDGSKSYYADSVQGRFTISRDN 
               
               
                   
                 SRNTVYLQMNSLRAEDTAMYYCARDRGTKWNQLNDVFDMWGQGTMVTVSS 
               
               
                   
               
               
                 SEQ ID 41 
                 QMQLVQSGAEVKKPGASVKVSCTASGYTFTSSDINWVRQATGQGLEWMGWMNPNSGNTGYAEKFQGRVT 
               
               
                   
                 MTSDSSISTAYMELRSLTTEDTAVYYCARGGGASYTDSWGQGTLVTVSS 
               
               
                   
               
               
                 SEQ ID 42 
                 QVQLVQSGGGLVQPGRSLRLSCTASGFTFGDYAMSWFRQAPGKGLEWVGEIRSKAYGGTTEYAASVKGRFTIS 
               
               
                   
                 RDDSKSIAYLQMNSLKTEDTAVYYCTAKGGYVGYSYGPFGGYWGQGTLVTVSS 
               
               
                   
               
               
                 SEQ ID 43 
                 QVQLVQSGGGLVQPGRSLRLSCTASGFTFGDYAMSWFRQAPGKGLEWVGEIRSKAYGGTTEYAASVKGRFTIS 
               
               
                   
                 RDDSKSIAYLQMNSLKTEDTAVYYCTRGGTMVRGFGFNYWGQGTLVTVSS 
               
               
                   
               
               
                 SEQ ID 44 
                 QVQLQQWGAGLLKPSETLSLTCAVYGGSFSGYYWSWIRQPPGKGLEWIGEINHSGSTNYNPSLKSRVTISVDTS 
               
               
                   
                 KNQFSLKLSSVTAADTAVYYCARARRAMIGPLPRLVGYFDLWGRGTLVTVSS 
               
               
                   
               
               
                 SEQ ID 45 
                 QVQLQQWGAGLLKPSETLSLTCAVYGGSFSGYYWSWIRQPPGKGLEWIGEINHSGSTNYNPSLKSRVTISVDTS 
               
               
                   
                 KNQFSLKLSSVTAADTAVYYCARGRPAPSWVKTRNWFDPWGQGTLVTVSS 
               
               
                   
               
               
                 SEQ ID 46 
                 QVQLQQSGPGLVKPSQTLSLTCAISGDSVSSNSAAWNWIRQSPSRGLEWLGRTYYRSKWYNDYAVSVKSRITI 
               
               
                   
                 NPDTSKNQFSLQLNSVTPEDTAVYYCAREASSGWNWGQGTLVTVSS 
               
               
                   
               
               
                 SEQ ID 47 
                 QVQLQESGPGLVKPSQTLSLTCAISGDSVSSNNAAWNWIRQSPSRGLEWLGRTFYRSKWYNDYAVSVKSRLTV 
               
               
                   
                 NPDTSKNQFSLRLNSVSPEDTAVYYCARGGRYTKGGYFDDWGQGTLVTVSS 
               
               
                   
               
               
                 SEQ ID 48 
                 QVTLKESGPTLVKPTQTLTLICTFSGFSLSTSGVGVGWIRQPPGKALEWLALIYWDDDKRYSPSLKSRLTITKDTS 
               
               
                   
                 KNQVVLTMTNMDPVDTATYYCAHRLDSSGRGGYFDYWGQGTLVTVSS 
               
               
                   
               
               
                 SEQ ID 49 
                 EVQLVESGGGVVQPGRSLRLSCTASGFTFSSYGMHWVRQAPGKGLEWVAVISYDGSNKYYADSVKGRFTISRD 
               
               
                   
                 NSKNTLYLQMNSLRAEDTAVYYCAKELVGTSSPYYYYYYGMDVWGQGTMVTVSS 
               
               
                   
               
               
                 SEQ ID 50 
                 QLQLQESGGGLVQPGGSLRLSCAASGFTVSSNYMSWVRQAPGKGLEWVSVIYSGGSTYYADSVKGRFTISRDN 
               
               
                   
                 SKNTLYLQMNSLRAEDTAVYYCARDYYYGSGSSPWGQGTLVTVSS 
               
               
                   
               
               
                 SEQ ID 51 
                 QVQLQQWGAGLLKPSETLSLTCAVYGGSFSGYYWSWIRQPPGKGLEWIGEINHSGSTNYNPSLKSRVTISVDTS 
               
               
                   
                 KNQFSLKLSSVTAADTAVYYCARGRPYCSSTSCYPEWFDPWGQGTLVTVSS 
               
               
                   
               
               
                 SE ID 52Q 
                 QVTLKESGGGVVQPGRSLRLSCAASGFTFSSYGMHWVRQAPGKGLEWVAVISYDGSNKYYADSVKGRFTISR 
               
               
                   
                 DNSKNTLYLQMNSLRAEDTAVYYCAKLRGIDYYDSSGYQRGFDYWGQGTLVTVSS 
               
               
                   
               
               
                 SEQ ID 53 
                 QVQLQESGPGLVKPSETLSLTCTVSGGSISSYYWSWIRQPPGKGLEWIGYIYYTGSTNYNPSLKSRVTISVDTSKN 
               
               
                   
                 QFSLKLSSVTTADTAVYYCARGGRGDGAAFDIWGQGTMVTVSS 
               
               
                   
               
               
                 SEQ ID 54 
                 QVQLVQSGGGVVQPGRSLRLSCAASGFTFSSSAMHWVRQAPGKGLEWVAMIWHDESKKYYADSVKGRFTIS 
               
               
                   
                 RDNSKNTLYLQMNSLRAEDTAVYYCARPPDGGNSGRWYFDLWGRGTLVTVSS 
               
               
                   
               
               
                 SEQ ID 55 
                 QMQLVQSGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRFTISR 
               
               
                   
                 DNSKNTLYLQMNSLRAEDTAVYYCAKDKNVRKHDYGDHPYGGYFDYWGQGTLVTVSS 
               
               
                   
               
               
                 SEQ ID 56 
                 EVQLVQSGAEVKKPGASVKVSCKASGYTFTSYAMHWVRQAPGQRLEWMGWINAGNGNTKYSQKFQGRVTI 
               
               
                   
                 TRDTSASTAYMELSSLRSEDTAVYYCARVAGATSLWYWGQGTLVTVSS 
               
               
                   
               
               
                 SEQ ID 57 
                 QVQLQQSGPGLVKPSQSLSLTCAISGDSVSSNSAAWNWIRQSPSRGLEWLGRTYYRSKWYNDYAVSVKSRITIK 
               
               
                   
                 PDTSKNQFSLQLNSVTPEDTAVYYCTRLANSDGVDVWGQGTMVTVSS 
               
               
                   
               
               
                 SEQ ID 58 
                 QVQLQQSGPGLVKPSQTLSLTCAISGDSVSSDSAVWTWIRQSPSRGLEWLGRTYYKSKWYNDYAASVKSRITIN 
               
               
                   
                 PDTSKNQFSLHLNSVTPEDTAVYYCARGVTRTFDYWGQGTTVTVSS 
               
               
                   
               
               
                 SEQ ID 59 
                 QLQLQESGPGLVKPSQTLSLTCAISGDSVSSNSAAWNWIRQSPSRGLEWLGRTYYRSKWYNDYAVSVKSRITIN 
               
               
                   
                 PDTSKNQFSLQLNSVTPEDTAVYYCAEGNGPFDPWGQGTLVTVSS 
               
               
                   
               
               
                 SEQ ID 60 
                 QITLKESGGGVVQPGRSLRLSCVASGFTFSTYPMHWVRQAPGKGLEWVAVISYDGRNEYYADSVKGRFTISRD 
               
               
                   
                 NSKNTLYLQMNSLRAEDTAVYYCATRDTPLVGVSIYWGQGTLVTVSS 
               
               
                   
               
               
                 SEQ ID 61 
                 QMQLVQSGGGLVKAGGSLRLSCSASGFTFSSYAMHWVRQAPGKGLEYVSAISSNGGSTYYADSVKGRFTISRD 
               
               
                   
                 NSKNTLYLQMSSLRAEDTAVYYCVNRAGYGDYRHFQHWGQGTLVTVSS 
               
               
                   
               
               
                 SEQ ID 62 
                 EVQLVQSGGGVVQPGGSLRLSCAASGFTFSSYGMHWVRQAPGKGLEWVAFISYDGSNKYYADSVKGRFTISR 
               
               
                   
                 DNSKNTLYLQMNSLRAEDTAVYYCATTGDRFQEFDYWGQGTLVTVSS 
               
               
                   
               
               
                 SEQ ID 63 
                 QMQLVQSGGVLLQPGRSLRLSCTASGFTFAAYNINWFRQGPGGGLEWVGEIRANADSGTTEYAASVKGRFFIS 
               
               
                   
                 RDDSRSTAYLQMTSLKTEDTAVYYCARDDRGRGDDFDYWGQGTLVTVSS 
               
               
                   
               
               
                 SEQ ID 64 
                 QVQLVQSGGGLVQPGGSLRLSCAASGFTFSSYGMTWVRQAPGKGLEWVSTISGNGVGTYYPDSVKDRFTISR 
               
               
                   
                 DSSKNTVYLQMNSLRAEDTAVYYCVKHGRAGINWYFDLWGRGTLVTVSS 
               
               
                   
               
               
                 SEQ ID 65 
                 QVQLQQSGPGLVKPSQTLSLTCAISGDSVSSNSAAWNWIRQSPSRGLEWLGRTYYRSKWYNDYAVSVKSRITI 
               
               
                   
                 NPDTSKNQFSLQLNSVTPEDTAVYYCARGGGLWAFDIWGQGTTVTVSS 
               
               
                   
               
               
                 SEQ ID 66 
                 EVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLEWMGWINPNSGGTNYAQKFQGRVT 
               
               
                   
                 MTRDTSISTAYMELSRLRSDDTAVYYCARDKIGSCPYWGQGTLVTVSS 
               
               
                   
               
               
                 SEQ ID 67 
                 QVTLKESGPTLVKPTQTLTLICTFSGFSLSTSGVGVGWIRQPPGKALEWLALIYWDDDKRYSPSLKSRLTITKDTS 
               
               
                   
                 KNQVVLTMTNMDPVDTATYYCAHRPDSSSQCFDYWGQGTLVTVSS 
               
               
                   
               
               
                 SEQ ID 68 
                 QVTLKESGGGVVQPGRSLRLSCAASGFTFSSYAMHWVRQAPGKGLEWVAVISYDGSNKYYADSVKGRFTISRD 
               
               
                   
                 NSKNTLYLQMNSLRAEDTAVYYCARSSGWSLPEDYWGQGTLVTVSS 
               
               
                   
               
               
                 SEQ ID 69 
                 QVQLVQSGAEVKKPGASVKVSCKVSGYTLTELSMHWVRQAPGKGLEWMGGFDPEDGETIYAQKFQGRVTM 
               
               
                   
                 TEDTSTDTAYMELSSLRSEDTAVYYCATDVNPELLGAGFDYWGQGTLVTVSS 
               
               
                   
               
               
                 SEQ ID 70 
                 QVTLKESGGGLVQPGGSLRLSCAASGFTFSDQYMDWVRQAPGKGLEWVGRVRNKANSYTTEYAASVKGRFTI 
               
               
                   
                 SRDDSKNSLYLQMNSLNTEDTAMYFCASSLNSGGYRCFHHWGQGTLVTVSS 
               
               
                   
               
               
                 SEQ ID 71 
                 QVQLVQSGGGLVQPGGSLRLSCSASGFTFSSYAMHWVRQAPGKGLEYVSAISSNGGSTYYADSVKGRFTISRD 
               
               
                   
                 NSKNTLYLQMSSLRAEDTAVYYCVKAPRGVVPAAMRGGYWGQGTLVTVSS 
               
               
                   
               
               
                 SEQ ID 72 
                 QVQLQESGGGLVQPGRSLRLSCTASGFTFGDYAMSWFRQAPGKGLEWVGEIRSKAYGGTTEYAASVKGRFTIS 
               
               
                   
                 RDDSKSIAYLQMNSLKTEDTAVYYCTRLVGNSGSYYPFGYWGQGTLVTVSS 
               
               
                   
               
               
                 SEQ ID 73 
                 QVQLQQWGAGLLKPSETLSLTCAVYGGSFSGYYWSWIRQPPGKGLEWIGEINHSGSTNYNPSLKSRVTISVDTS 
               
               
                   
                 KNQFSLKLSSVTAADTAVYYCARGRSLPYRGLAPRSEGGYYFDYWGQGTLVTVSS 
               
               
                   
               
               
                 SEQ ID 74 
                 QVQLQESGGGLVRPGGSLRLSCGDSGFNFSGYEMNWVRQAPGKGLEWVSYVSTSGSTRYYADSVKGRFTISR 
               
               
                   
                 DNAKNTLYLQMNSLRVEDTAVYYCARGRTHWGPQDFDYWGQGTLVTVSS 
               
               
                   
               
               
                 SEQ ID 75 
                 QVQLQESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRFTISRD 
               
               
                   
                 NSKNTLYLQMNSLRAEDTAVYYCAKGGMYYYGSGSSYFDYWGQGTLVTVSS 
               
               
                   
               
               
                 SEQ ID 76 
                 QVQLVQSGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSGISGSGGSTYYADSVKGRFTISR 
               
               
                   
                 DNSKNMLFLQMNSPRAEDTAVYYCAKKIAAAGKQPVDYWGQGTLVTVSS 
               
               
                   
               
               
                 SEQ ID 77 
                 QVQLQQWGAGLLKPSETLSLTCAVYGGSFSGYYWSWIRQPPGKGLEWIGEINHSGSTNYNPSLKSRVTISVDTS 
               
               
                   
                 KNQFSLKLSSVTAADTAVYYCARRKVYDYVWGSYRLPGSVSYYFDYWGQGTLVTVSS 
               
               
                   
               
               
                 SEQ ID 78 
                 QVQLVQSGAEVKKPGESLKISCKGSGYSFTSYWIGWVRQMPGKGLEWMGIIYPGDSDTRYSPSFQGQVTISAD 
               
               
                   
                 KSISTAYLQWSSLKASDTAMYYCARLPGRAARPDYWGQGTLVTVSS 
               
               
                   
               
               
                 SEQ ID 79 
                 QVTLKESGGGVVQPGRSLRLSCAASGFTFSSYAMHWVRQAPGKGLEWVAVISYDGSNKYYADSVKGRFTISRD 
               
               
                   
                 NSKNTLYLQMNSLRAEDTAVYYCARGPGAVAGTKPKYYFDYWGQGTLVTVSS 
               
               
                   
               
               
                 SEQ ID 80 
                 EVQLVQSGGGVVQPGRSLRLSCAASGFTFSSYAMHWVRQAPGKGLEWVAVISYDGSNKYYADSVKGRFTISR 
               
               
                   
                 DNSKNTLYLQMNSLRAEDTAVYYCARATYYYDSSGYRFDYWGQGTLVTVSS 
               
               
                   
               
               
                 SEQ ID 81 
                 EVQLVQSGGGLVEPGGSLRLSCAASRFTFSDAWMSWVRQAPGKGLEWVGRIKSKISGGTTDYAAPVQGRFTI 
               
               
                   
                 SRDDSKNTLYLQMDSLKTEDTAVYYCANRNLGYWGQGTLVTVSS 
               
               
                   
               
               
                 SEQ ID 82 
                 EVQLVQSGAEVKKPGASVKVSCKASGYTFTSYAMHWVRQAPGQRLEWMGWINAGNGNTKYSQKFQGRVT 
               
               
                   
                 MTTDTSTSTAYMELRSLRSDDTAVYYCARARYYDSSGYIAPSGYFDYWGQGTLVTVSS 
               
               
                   
               
               
                 SEQ ID 83 
                 QVQLVQSGAEVKKPGASVKVSCKASGYTFTSYAMHWVRQAPGQRLEWMGWINAGNGNTKYSQKFQGRVT 
               
               
                   
                 ITRDTSASTAYMELSSLRSEDTAVYYCARDGPAVDGAEYFQHWGQGTLVTVSS 
               
               
                   
               
               
                 SEQ ID 84 
                 QLQLQESGPGLVKPSQTLSLTCAISGDSVSSNSAAWNWIRQSPSRGLEWLGRTYYRSKWYNDYAVSLKSRITIN 
               
               
                   
                 PDTSKNQFSLQLNSVTPEDTAVYYCASLASGSPPPGDYWGQGTLVTVSS 
               
               
                   
               
               
                 SEQ ID 85 
                 QVTLKESGGGVVQPGRSLRLSCAASGFTFSTYGMHWVRQAPGKGLEWVALISYDGSKKYYANSVKGRFTISRD 
               
               
                   
                 NSKNTLYLQMKSLRAEDTAMYYCAKGPIVGATMDYWGQGALVTVSS 
               
               
                   
               
               
                 SEQ ID 86 
                 EVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAISWVRQAPGQGLEWMGWISAYNGNTNYAQKLQGRVTM 
               
               
                   
                 TTDTSTSTAYMELRSLRSDDTAVYYCARWYGDYGLDYWGQGTLVTVSS 
               
               
                   
               
               
                 SEQ ID 87 
                 EVQLVQSGAEVKKPGASVKVSCKASGYTFTSYAMHWVRQAPGQRLAWMGWINAGNGNTKYSEKFEGRVTI 
               
               
                   
                 TRDTSASTAYMELSSLRSEDTAVYYCARVAKYYYESGGYRASNWFDPWGQGTLVTVSS 
               
               
                   
               
               
                 SEQ ID 88 
                 QVQLQESGPGLVKPSQTLSLTCAISGDSVSSNSAAWNWIRQSPSRGLEWLGRTYYRSKWYNDYAVSVKSRITIN 
               
               
                   
                 PDTSKNQFSLQLNSVTPEDTAVYYCARAPPPTVGWYAPVFDYWGQGTLVTVSS 
               
               
                   
               
               
                 SEQ ID 89 
                 QLQLQESGGGLVQPGGSLRLSCSASGISFRDYWMHWIRQTPGKGLVWVSRINPDGSSTSYADSVKGRFTISRD 
               
               
                   
                 NSKNTLYLQMNSLRAEDTAVYYCAKVTGRRVGAHDYWGQGTLVTVSS 
               
               
                   
               
               
                 SEQ ID 90 
                 QVQLVQSGAEVKKPGASVKVSCKASGYTFTGYYMHWVRQAPGQGLEWMGWINPNSGGTNYAQKFQGRVT 
               
               
                   
                 MTRDTSISTAYMELSRLRSDDTAVYYCAFAQPGAETLNFDLWGRGTLVTVSS 
               
               
                   
               
               
                 SEQ ID 91 
                 QVQLQQSGPGLVKPSQTLSLTCAISGDSVSSKSAAWNWIRQSPSRGLEWLGRTYYRSKWNNDYALSVKSRITI 
               
               
                   
                 NPDTSKNQFSLQLKSVTPEDTALYYCVRQVAGGMDVWGQGTTVTVSS 
               
               
                   
               
               
                 SEQ ID 92 
                 QVQLVQSGGGLVQPGRSLRLSCTASGFTFGDYAMSWFRQAPGKGLEWVSAISGSGGSTYYADSVKGRFTISR 
               
               
                   
                 DNSKNTLYLQMNSLRAEDTAVYYCAKGSVYSGSYYMLIDYWGQGTLVTVSS 
               
               
                   
               
               
                 SEQ ID 93 
                 QVQLQQSGPGLVRPSQTLSLTCVISGDSVSSGSAAWNWIRQSPSRGLEWLGRTYYRAKWYNEYAGSVKSRITIS 
               
               
                   
                 PDTSKNQFSLQLNSVTPEDTAVYFCTRQDKDNTRYSGLGVWGQGTTVTVSS 
               
               
                   
               
               
                 SEQ ID 94 
                 EVQLVETGGGLVQPGGSLRLSCAASEFTLRNYGVSWVRQAPGKGLEWVSGMSGSGYSTYYADSVKGRFTISR 
               
               
                   
                 DSSKNTLFLQMDSLRAEDTAIYYCARGPRMWSSGIDAFDIWGHGTMVTVSS 
               
               
                   
               
               
                 SEQ ID 95 
                 QVQLQQWGAGLLKPSETLSLTCAVYGGSVSGYYWSWIRQPPGKGLEWMGEIHHSGSTNYNPSLKSRVTISLDT 
               
               
                   
                 PKNQFSLKLSSVTAADTAVYYCARRDWAGKRVWGQGTLVTVSS 
               
               
                   
               
               
                 SEQ ID 96 
                 QVQLQQSGPGLLKPSQTLSLTCAISGDSVSSNTATWNWIRQSPSRGLEWLGRTYYRSKWYKDNALSVKSRITIN 
               
               
                   
                 PDTSKNQFSLQLNSVTPEDTAVYYCAGGRAGIAAFDIWGQGTTVTVSS 
               
               
                   
               
               
                 SEQ ID 97 
                 QVQLVQSGGGLIQPGGSLRLSCAASGFTVSSNYMSWVRQAPGKGLEWVSLIYSDGRTNYADSVKGRFTISRDN 
               
               
                   
                 SKNTLYLQMNSLRAEDTAVYYCAKGALQGEWRRFDYWGQGTLVTVSS 
               
               
                   
               
               
                 SEQ ID 98 
                 QVQLQQSGPGLVKPSQTLSLTCAISGDSVSSNSAAWNWIRQSPSRGLEWLGRTYYRSKWYNDYAVSVKSRITI 
               
               
                   
                 NPDTSKNQFSLQLNSVTPEDTAVYYCTRTNQGYGGNSGVFDYWGQGTLVTVSS 
               
               
                   
               
               
                 SEQ ID 99 
                 QVQLQQSGPGLVKPSQTLSLTCAISGDSVSGNSAAWNWIRQSPSRGLEWLGRTYYRSKWYNDYAVSVKSRITI 
               
               
                   
                 NPDTSKNQFSLQLNSVTPEDTAVYYCARIVGGAVDCWGQGTLVTVSS 
               
               
                   
               
               
                 SEQ ID 100 
                 EVQLVQSGAEVKKPGASVKVSCKASGYTFTSYAMHWVRQAPGQRLEWMGWINAGNGNTKYSQKFQGRVTI 
               
               
                   
                 TRDTSASTAYMELSSLRSEDTAVYYCARVRVGATTVYDSWFDPWGQGTLVTVSS 
               
               
                   
               
               
                 SEQ ID 101 
                 QVQLVQSGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSAISGSGGSTYYADSVKGRFTISRD 
               
               
                   
                 NSKNTLYLQMNSLRAEDTAVYYCAKDGGSSPYYDSSGLLPWYFDLWGRGTLVTVSS 
               
               
                   
               
               
                 SEQ ID 102 
                 QVQLQESGGGLVQPGGSLRLSCAASGFTFSSYAMHWVRQAPGKGLEYVSAISSNGGSTYYANSVKGRFTISRD 
               
               
                   
                 NSKNTLYLQMGSLRAEDMAVYYCARAKFWTYYFDYWGQGTLVTVSS 
               
               
                   
               
               
                 SEQ ID 103 
                 QVQLQQWGAGLLKPSETLSLTCAVYGGSFSGYYWSWIRQPPGKGLEWIGEINHSGSTNYNPSLKSRVTISVDTS 
               
               
                   
                 KNQFSLKLSSVTAADTAVYYCARGGGSGSYYKRFFDYWGQGTLVTVSS 
               
               
                   
               
               
                 SEQ ID 104 
                 EVQLVQSGAEVRKPGASVKVSCKASGYTFTSYAISWVRQAPGQGLEWMGWISAYDGNTNYAQKLQGRVTM 
               
               
                   
                 TTDTSTSTAYMEVRSLRSDDTAVYYCARDGTVRRVVGATTPGNFDYRGQGTLVTVSS 
               
               
                   
               
               
                 SEQ ID 105 
                 EVQLVQSGGGVVQPGRSLRLSCAASGFTFSSYGMHWVRQAPGKGLEWVAVIWYDGSNKYYADSVKGRFTIS 
               
               
                   
                 RDNSKNTLYLQMNSLRAEDTAVYYCARDLNRGYCSGGSCFGYWGQGTLVTVSS 
               
               
                   
               
               
                 SEQ ID 106 
                 QVQLQESGGGLVQPGGSLRLSCAASGFTFSSYAMSWVRQAPGKGLEWVSYISSSGTTIYYADSVKGRFTVSRD 
               
               
                   
                 NAKNSLYLQMNSLRAEDTAVYYCARDYSSSGECFDYWGQGTLVTVSS 
               
               
                   
               
               
                 SEQ ID 107 
                 EVQLVQSGGGVVQPGRSLRLSCAASGFTFSSYGMHWVRQAPGKGLEWVAVIWYDGSNKYYADSVKGRFTIS 
               
               
                   
                 RDNSKNTLYLQMNSLRAEDTAVYYCARDQAAMVGYFDYWGQGTLVTVSS 
               
               
                   
               
               
                 SEQ ID 108 
                 QVTLKESGGGVVQPGRSLRLSCAASGFlFSNYAIHWVRQAPGKGLEWVAVISYDGSNKYYADSVKGRFTISRDN 
               
               
                   
                 SKNTLYLQMNSLRAEDTAVYYCARTFAGYSSKLGYFDLWGRGTLVTVSS 
               
               
                   
               
            
           
         
       
     
     A VH amino acid sequence of the disclosure may be encoded by a polynucleotide shown in Table 3 below. 
     
       
         
           
               
             
               
                 TABLE 3 
               
             
            
               
                   
               
               
                 VH DNA Sequences 
               
            
           
           
               
               
            
               
                 SEQ ID 
                 VH DNA Sequence 
               
               
                   
               
               
                 SEQ ID 
                 GAAGTGCAGCTGGTGCAGTCTGGGGCTGAGGTGAAGAAGCCTGGGGCCTCAGTGAAGG 
               
               
                 109 
                 TTTCCTGCAAGGCTTCTGGATACACCTTCACTAGCTATGCTATGCATTGGGTGCGCCAGG 
               
               
                   
                 CCCCCGGACAAAGGCTTGAGTGGATGGGATGGATCAACGCTGGCAATGGTAACACAAA 
               
               
                   
                 ATATTCACAGAAGTTCCAGGGCAGAGTCACCATTACCAGGGACACATCCGCGAGCACAG 
               
               
                   
                 CCTACATGGAGCTGAGCAGCCTGAGATCTGAAGACACGGCTGTGTATTACTGTGCGAGA 
               
               
                   
                 GGCTCCTTGTCCCGAAGTGGCTGGTACGCCGGACTCTTTGACTACTGGGGCCAGGGAAC 
               
               
                   
                 CCTGGTCACCGTCTCCTCA 
               
               
                   
               
               
                 SEQ ID 
                 CAGATCACCTTGAAGGAGTCTGGGGGAGGCGTGGTCCAGCCTGGGAGGTCCCTGAGACT 
               
               
                 110 
                 CTCCTGTGCAGCCTCTGGATTCACCTTCAGTAGTTATAGCATGAACTGGGTCCGCCAGGC 
               
               
                   
                 TCCAGGCAAGGGGCTGCAGTGGGTGGCAATTATATCAGATGATGGAAGTAAGAGTTACT 
               
               
                   
                 ACGCAGACTCCGTGCAGGGCCGATTCACCATCTCCAGAGACAATTCGAGGAACACAGTA 
               
               
                   
                 TTTCTGCAAATGAACAGCCTGAGAGCTGAGGACACGGCTATGTATTACTGTGCGAGAGA 
               
               
                   
                 CAGGGGAACTAAATGGAACCAATTGAATGATGTTTTTGATATGTGGGGCCAAGGGACAA 
               
               
                   
                 TGGTCACCGTCTCTTCA 
               
               
                   
               
               
                 SEQ ID 
                 GAAGTGCAGCTGGTGCAGTCTGGGGCTGAGGTGAAGAAGCCTGGGGCCTCAGTGAAGG 
               
               
                 111 
                 TTTCCTGCAAGGCATCTGGATACACCTTCACCAGCTACTATATGCACTGGGTGCGACAGG 
               
               
                   
                 CCCCTGGACAAGGGCTTGAGTGGATGGGAATAATCAACCCTAGTGGTGGTAGCACAAGC 
               
               
                   
                 TACGCACAGAAGTTCCAGGGCAGAGTCACCATGACCAGGGACACGTCCACGAGCACAG 
               
               
                   
                 TCTACATGGAGCTGAGCAGCCTGAGATCTGAGGACACGGCCGTGTATTACTGTGCGAGA 
               
               
                   
                 GGCCGAGGGTATAGCAGCAGTCGGCTCTACTACTTTGACTACTGGGGCCAGGGAACCCT 
               
               
                   
                 GGTCACCGTCTCCTCA 
               
               
                   
               
               
                 SEQ ID 
                 CAGGTCACCTTGAAGGAGTCTGGGGGAGGCTTGGTCCGGCCTGGAGGGTCCCTGAGACT 
               
               
                 112 
                 CTCCTGTGAAGCCTCTGGATTCACCTTCAGTGACCCCTACATGGACTGGGTCCGCCAGGC 
               
               
                   
                 TCCAGGCAAGGGGCTGGAGTGGGTTGGCCGAATTACAAATAAGCGTACCGGTTACGCCA 
               
               
                   
                 CAACATATGCCGCGTCTGTGAAGGACAGATTCACCATCTCAAGAGATGATTCAAGGAAG 
               
               
                   
                 TCAGTATATCTGCAAATGAACAGCCTGAAGACCGAGGACACGGCCGTATATTATTGTGC 
               
               
                   
                 AACAGATGTCAGTGGGTCCTTCGCGGCCTACGGGGGCCAGGGCACCCTGGTCACCGTCT 
               
               
                   
                 CCTCA 
               
               
                   
               
               
                 SEQ ID 
                 GAGGTCCAGCTGGTACAGTCTGGGGGAGGCGTGGTCCAGCCTGGGAGGTCCCTGAGACT 
               
               
                 113 
                 CTCCTGTGCAGCGTCTGGATTCACCTTCAGTAGCTATGCTATGCATTGGGTGCGCCAGGC 
               
               
                   
                 CCCCGGACAAAGGCTTGAGTGGATGGGATGGATCAACGCTGGCAATGGTAACACAAAA 
               
               
                   
                 TATTCACAGAAGTTCCAGGGCAGAGTCACCATTACCAGGGACACATCCGCGAGCACAGC 
               
               
                   
                 CTACATGGAGCTGAGCAGCCTGAGATCTGAAGACACGGCTGTGTATTACTGTGCGGGAG 
               
               
                   
                 AGGGCGGAGCAGTGGCTGGTACTGTCTACTGGGGCCAGGGAACCCTGGTCACCGTCTCC 
               
               
                   
                 TCA 
               
               
                   
               
               
                 SEQ ID 
                 CAGGTCCAGCTGGTGCAGTCTGGGGGAGGCTTGGTAAAGCCTGGGGGGTCCCTTAGACT 
               
               
                 114 
                 CTCCTGTGCAGCCTCTGGATTCACTTTCAGTAACGCCTGGATGAGCTGGGTCCGCCAGGC 
               
               
                   
                 TCCAGGGAAGGGGCTGGAGTGGGTTGGCCGTATTAAAAGCAAAACTGATGGTGGGACA 
               
               
                   
                 ACAGACTACGCTGCACCCGTGAAAGGCAGATTCACCATCTCAAGAGATGATTCAAAAAA 
               
               
                   
                 CACGCTGTATCTGCAAATGAACAGCCTGAAAACCGAGGACACAGCCGTGTATTACTGTA 
               
               
                   
                 CCACAGACGAGTATTTCTACTGGGGCCAGGGAACCCTGGTCACCGTCTCCTCA 
               
               
                   
               
               
                 SEQ ID 
                 CAGGTGCAGCTACAGCAGTGGGGCGCAGGACTGTTGAAGCCTTCGGAGACCCTGTCCCT 
               
               
                 115 
                 CACCTGCGCTGTCTATGGTGGGTCCTTCAGTGGTTACTACTGGAGCTGGATCCGCCAGCC 
               
               
                   
                 CCCAGGGAAGGGGCTGGAGTGGATTGGGGAAATCAATCATAGTGGAAGCACCAACTAC 
               
               
                   
                 AACCCGTCCCTCAAGAGTCGAGTCACCATATCAGTAGACACGTCCAAGAACCAGTTCTC 
               
               
                   
                 CCTGAAGCTGAGCTCTGTGACCGCCGCGGACACGGCTGTGTATTACTGTGCGAGAGTAA 
               
               
                   
                 ATCCGGGGAGTTATACGAGGGAGGTGAGCAACTTTGACTACTGGGGCCAGGGAACCCTG 
               
               
                   
                 GTGACCGTCTCCTCA 
               
               
                   
               
               
                 SEQ ID 
                 CAGGTACAGCTGCAGCAGTCAGGTCCAGAATTGGTGAAGCCCTCGCAGACCCTCACACT 
               
               
                 116 
                 CACCTGTGGCATCTCCGGGGACAGTGTCTCTAGCAACAGTGTTACTTGGAACTGGGTCA 
               
               
                   
                 GGCAGTCCCCATCGAGAGGCCTTGAGTGGCTGGGAAGGACTTACTACCGGTCCCAGTGG 
               
               
                   
                 TATTATAATTATGCGGTGTCTGTGAAAAGTCGAATAACCATCAGCCCAGACACATCCAA 
               
               
                   
                 GAACCAGTTCTCCCTGCAGTTGAATTCTGTGACTCCCGAGGACACGGCTGTCTATTACTG 
               
               
                   
                 TGCAACCAGGGGACATAACTACGGTGTAGATTACTGGGGCCCGGGGACCACGGTCACCG 
               
               
                   
                 TCTCCTCA 
               
               
                   
               
               
                 SEQ ID 
                 CAGGTGCAGCTGGTGCAGTCTGGGGGAGGCTTGGTAAAGCCTGGGGGGTCCCTTAGACT 
               
               
                 117 
                 CTCCTGTGCAGCCTCTGGATTCACTTTCAGTAACGCCTGGATGAGCTGGGTCCGCCAGGC 
               
               
                   
                 TCCAGGGAAGGGGCTGGAGTGGGTTTGCCGTATTAAAAGCAAAACTGATGGTGAGACA 
               
               
                   
                 ACAGACTACGCTGCACCCGTGAAAGGCAGATTCACCATCTCAAGAGATGATTCAAAAAA 
               
               
                   
                 CACGCTGTATCTGCAAATGAACAGCCTGAAAACTGAGGACACAGCCGTGTATCACTGTA 
               
               
                   
                 CCACAGGGGTGGGATGGTCGCCCTTCCAATACTGGGGCCAGGGCACCCTGGTCACCGTC 
               
               
                   
                 TCCTCA 
               
               
                   
               
               
                 SEQ ID 
                 GAGGTCCAGCTGGTACAGTCTGGGGGAGGCTTGGTACAGCCAGGGCGGTCCCTGAGACT 
               
               
                 118 
                 CTCCTGTACAGCTTCTGGATTCACCTTTGGTGATTATGCTATGAGCTGGTTCCGCCAGGC 
               
               
                   
                 TCCAGGGAAGGGGCTGGAGTGGGTAGGTTTCATTAGAAGCAAAGCTTATGGTGGGACAA 
               
               
                   
                 CAGAATACGCCGCGTCTGTGAAAGGCAGATTCACCATCTCAAGAGATGATTCCAAAAGC 
               
               
                   
                 ATCGCCTATCTGCAAATGAACAGCCTGAAAACCGAGGACACAGCCGTGTATTACTGTAC 
               
               
                   
                 TAGAGACGACAAAATAGCAGCAGCTGGATTCACATACTGGTACTTCGATCTCTGGGGCC 
               
               
                   
                 GTGGCACCCTGGTCACCGTCTCCTCA 
               
               
                   
               
               
                 SEQ ID 
                 CAGGTGCAGCTGGTGCAGTCTGGGGCTGAGGTGAAGAAGCCTGGGGCCTCAGTGAAGGT 
               
               
                 119 
                 CTCCTGCAAGGCTTCTGGATACACCTTCGCCGCCTATTATTTACACTGGGTGCGACAGGC 
               
               
                   
                 CCCTGGACAAGGCCTTGAGTGGATGGGGCGGATCAGCCCTGGTAACGGTGTCACAAGTT 
               
               
                   
                 ATGCACAGAAATTTCAGGGCAGAGTCACCATGACCGGGGACACGTCCATTAACACAGTC 
               
               
                   
                 TACATGCAACTGAACAATTTGATTTCTGGCGACACGGCCGTATATTACTGTGCGAGAGA 
               
               
                   
                 GGCTGCCGACGACCCGTTTGACCATTGGGGCCAGGGAGCCCTGGTCACCGTCTCCTCA 
               
               
                   
               
               
                 SEQ ID 
                 GAAGTGCAGCTGGTGCAGTCTGGGGGAGGCGTGGTCCAGCCTGGGAGGTCCCTGACACT 
               
               
                 120 
                 CTCCTGTGCAGCCTCTGGATTCACCTTCAGTTCCCATCTTATGCACTGGGTCCGCCAGGC 
               
               
                   
                 TCCAGGCAAGGGGCTGGAGTGGGTGGCAGTTATATCATATGATGGAACTAGTAAATATT 
               
               
                   
                 ACGGAGACTCCGTGAAGGGCCGCTTCACCATCTCCAGAGACAATTCCAAGAACACGTTG 
               
               
                   
                 TATCTGCAAATGAACAGCCTGCGAGCTGAAGACACGGCTATATATTACTGTGCGAAAGC 
               
               
                   
                 AGATTATAAATATGACTGGGGCCAGGGAACCCTGGTCACCGTCTCCTCA 
               
               
                   
               
               
                 SEQ ID 
                 GAGGTGCAGCTGGTGCAGTCTGGGGGAGGCTTGGTCAAGCCTGGAGGGTCCCTGAGACT 
               
               
                 121 
                 CTCCTGTACAGCTTCTGGATTCACCTTTGGTGATTATGCTATGAGCTGGGTCCGCCAGGC 
               
               
                   
                 TCCAGGGAAGGGGCTGGAGTGGGTAGGTTTCATTAGAAGCAAAGCTTATGGTGGGACAA 
               
               
                   
                 CAGAATACGCCGCGTCTGTGAAAGGCAGATTCACCATCTCAAGAGATGATTCCAAAAGC 
               
               
                   
                 ATCGCCTATCTGCAAATGAACAGCCTGAAAACCGAGGACACAGCCGTGTATTACTGTAC 
               
               
                   
                 TACTCATAGACGCCCAATTTACGATATTTTGACTGGTTTTGACTACTGGGGCCAGGGAAC 
               
               
                   
                 CCTGGTCACCGTCTCCTCA 
               
               
                   
               
               
                 SEQ ID 
                 CAGCTGCAGCTGCAGGAGTCCGGGGGAGGCTTGGTACAGCCAGGGCGGTCCCTGAGACT 
               
               
                 122 
                 CTCCTGTACAGCTTCTGGATTCACCTTTGGTGATTATGCTATGAGCTGGGTCCGCCAGGC 
               
               
                   
                 TCCAGGGAAGGGGCTGGAGTGGGTAGGTTTCATTAGAAGCAAAGCTTATGGTGGGACAA 
               
               
                   
                 CAGAATACGCCGCGTCTGTGAAAGGCAGATTCACCATCTCAAGAGATGATTCCAAAAGC 
               
               
                   
                 ATCGCCTATCTGCAAATGAACAGCCTGAAAACCGAGGACACAGCCGTGTATTACTGTAC 
               
               
                   
                 TAGAGAGGATACTATGGTTCGGGGAGTTATTCCCTGGGGCCAGGGAACCCTGGTCACCG 
               
               
                   
                 TCTCCTCA 
               
               
                   
               
               
                 SEQ ID 
                 CAGCTGCAGCTGCAGGAGTCCGGCTCAGGACTGGTGAAGCCTTCACAGACCCTGTCCCT 
               
               
                 123 
                 CACCTGCGCTGTCTCTGGTGGCTCCATCAGCAGTGGTGGTTACTCCTGGAGCTGGATCCG 
               
               
                   
                 GCAGCCACCAGGGAAGGGCCTGGAGTGGATTGGGTACATCTATCATAGTGGGAGCACCT 
               
               
                   
                 ACTACAACCCGTCCCTCAAGAGTCGAGTCACCATATCAGTAGACAGGTCCAAGAACCAG 
               
               
                   
                 TTCTCCCTGAAGCTGAGCTCTGTGACCGCCGCGGACACGGCTGTGTATTACTGTGCGAGA 
               
               
                   
                 GATCGGCGTTACTATGATAGTAGTGGTTATTATCCCGCCTACTACTTTGACTACTGGGGC 
               
               
                   
                 CAGGGAACCCTGGTCACCGTCTCCTCA 
               
               
                   
               
               
                 SEQ ID 
                 GAAGTGCAGCTGGTGCAGTCTGGGGGAGGCCTGGTCAAGCCTGGGGGGTCCCTGAGACT 
               
               
                 124 
                 CTCCTGTGCAGCCTCTGGATTCACCTTCAGTAGCTATAGCATGAACTGGGTCCGCCAGGC 
               
               
                   
                 TCCAGGGAAGGGGCTGGAGTGGGTTTCATACATTAGTAGTAGTGGTAGTTACACAAACT 
               
               
                   
                 ACGCAGACTCTGTGAAGGGCCGATTCACCATCTCCAGAGACAACGCCAAGAACTCACTG 
               
               
                   
                 TATCTGCAAATAAACAGCCTGAGAGCCGAGGACACGGCCATTTATTACTGTGCGAGAGA 
               
               
                   
                 CGGGGGCTATGATAGTAGTGGTTTTCACTTTGACTACTGGGGCCAGGGAACCCTGGTCA 
               
               
                   
                 CCGTCTCCTCA 
               
               
                   
               
               
                 SEQ ID 
                 CAGGTACAGCTGCAGCAGTCAGGTCCAGGACTGGTGAAGCCCTCGCAGACCCTCTCACT 
               
               
                 125 
                 CACCTGTGCCATCTCCGGGGACAGTGTCTCTAACAACAGGGCTGCTTGGAACTGGATCA 
               
               
                   
                 GGCAGTCGCCATCGAGAGGCCTTGAGTGGCTGGGAAGGACATACTACAGGTCCAAGTGG 
               
               
                   
                 TATAATGAATATGCAGTCTCTGTGAAAAGTCGAATAACCATCAACCCAGACACATCCAA 
               
               
                   
                 GAACCAGTTCTCCCTGCAGCTGAACTCTATGACTCCCGAGGACTCGGCTGTGTATTACTG 
               
               
                   
                 TGCAATTTTGCCTAGTAGTGGTTATCTACAGGACCACCACTACTACGGTATGGACGTCTG 
               
               
                   
                 GGGCCAAGGGACCACGGTCACCGTCTCCTCA 
               
               
                   
               
               
                 SEQ ID 
                 GAGGTGCAGCTGGTGCAGTCTGGAGCTGAGGTGAAGAAGCCTGGGGCCTCAGTGAAGG 
               
               
                 126 
                 TCTCCTGCAAGGCTTCTGGTTACACCTTTACCAGCTACGGTATCAGCTGGGTGCGACAGG 
               
               
                   
                 CCCCTGGACAAGGGCTTGAGTGGATGGGATGGATCAGCGCTTACAATGGTAACACAAAC 
               
               
                   
                 TATGCACAGAAGCTCCAGGGCAGAGTCACCATGACCACAGACACATCCACGAGCACAG 
               
               
                   
                 CCTACATGGAGCTGAGCAGCCTGAGATCTGAGGACACGGCCGTGTATTACTGTGCGAGA 
               
               
                   
                 GCCGCGGTGGGGGATGGATACAGCTATGGTCGGCTCGATTGGGGCCAGGGAACCCTGGT 
               
               
                   
                 CACCGTCTCCTCA 
               
               
                   
               
               
                 SEQ ID 
                 GAGGTCCAGCTGGTACAGTCTGGAGCAGAGGTGAAAAAGCCCGGGGAGTCTCTGAAGA 
               
               
                 127 
                 TCTCCTGTAAGGGTTCTGGATACAGCTTTACCAGCTACTGGATCGGCTGGGTGCGCCAGA 
               
               
                   
                 TGCCCGGGAAAGGCCTGGAGTGGATGGGGATCATCTATCCTGGTGACTCTGATACCAGA 
               
               
                   
                 TACAGCCCGTCCTTCCAAGGCCAGGTCACCATCTCAGCCGACAAGTCCATCAGCACCGC 
               
               
                   
                 CTACCTGCAGTGGAGCAGCCTGAAGGCCTCGGACACCGCCATGTATTACTGTGCGAGAC 
               
               
                   
                 TCCCCTCGTATTACTATGATAGTAGTGGTTACTTTACCTGGTACTTCGATCTCTGGGGCCG 
               
               
                   
                 TGGCACCCTGGTGACCGTCTCTTCA 
               
               
                   
               
               
                 SEQ ID 
                 GAGGTCCAGCTGGTACAGTCTGGAGCTGAGGTGAAGAAGCCTGGGGCCTCAGTGAAGGT 
               
               
                 128 
                 CTCCTGCAAGGCTTCTGGTTACACCTTTACCAGCTATGGTATCAGCTGGGTGCGACAGGC 
               
               
                   
                 CCCTGGACAAGGGCTTGAGTGGATGGGATGGATCATCCCTATCTTTGGTATAGCAAACT 
               
               
                   
                 ACGCACAGAAGTTCCAGGGCAGAGTCACGATTACCGCGGACAAATCCACGAGCACAGC 
               
               
                   
                 CTACATGGAGCTGAGCAGCCTGAGATCTGAGGACACGGCCGTGTATTACTGTGCGAGAG 
               
               
                   
                 AACTATACAACTATGGTTCAAAGGACTACTTTGACTACTGGGGCCAGGGAACCCTGGTC 
               
               
                   
                 ACCGTCTCCTCA 
               
               
                   
               
               
                 SEQ ID 
                 GAAGTGCAGCTGGTGCAGTCTGGAGCAGAGGTGAAAAAGCCCGGGGAGTCTCTGAAGA 
               
               
                 129 
                 TCTCCTGTAAGGGTTCTGGATACAGCTTTACCAGCTACTGGATCGGCTGGGTGCGCCAGA 
               
               
                   
                 TGCCCGGGAAAGGCCTGGAGTGGATGGGGATCATCTATCCTGGTGACTCTGATACCAGA 
               
               
                   
                 TACAGCCCGTCCTTCCAAGGCCAGGTCACCATCTCAGCCGACAAGTCCATCAGCACCGC 
               
               
                   
                 CTACCTGCAGTGGAGCAGCCTGAAGGCCTCGGACACCGCCATGTATTACTGTGCGAGGG 
               
               
                   
                 GCGGTACTTGGGATACAGCTATGGTTACGGGCTTTGACTACTGGGGCCAGGGAACCCTG 
               
               
                   
                 GTCACCGTCTCCTCA 
               
               
                   
               
               
                 SEQ ID 
                 GAAGTGCAGCTGGTGCAGTCTGGAGCAGAGGTGAAAAAGCCCGGGGAGTCTCTGAAGA 
               
               
                 130 
                 TCTCCTGTAAGGGTTCTGGATACAGCTTTACCAGCTACTGGATCGCCTGGGTGCGCCAGA 
               
               
                   
                 TGCCCGGGAAAGGCCTGGAGTGGATGGGGGTCATCTATCCTGGTGACTCTGATACCAGA 
               
               
                   
                 TACAGCCCGTCCTTCCAAGGCCAGGTCACCATCTCAGCCGACAAGTCCATCAATACCGC 
               
               
                   
                 CTACCTGCAGTGGAGCAGCCTGAAGGCCTCGGACACCGCCATGTATTACTGTGCGAGAC 
               
               
                   
                 CCCATTACGATATTTTGACTGGTTCCCGGGCGCCCTTTGACTACTGGGGCCAGGGAACCC 
               
               
                   
                 TGGTCACCGTCTCCTCA 
               
               
                   
               
               
                 SEQ ID 
                 CAGGTGCAGCTACAGCAGTGGGGCGCAGGACTGTTGAAGCCTTCGGAGACCCTGTCCCT 
               
               
                 131 
                 CACCTGCGCTGTCTATGGTGGGTCCTTCAGTGGTTACTACTGGAGCTGGATCCGCCAGCC 
               
               
                   
                 CCCAGGGAAGGGGCTGGAGTGGATTGGGGAAATCAATCATAGTGGAAGCACCAACTAC 
               
               
                   
                 AACCCGTCCCTCAAGAGTCGAGTCACCATATCAGTAGACACGTCCAAGAACCAGTTCTC 
               
               
                   
                 CCTGAAGCTGAGCTCTGTGACCGCCGCGGACACGGCTGTGTATTACTGTGCGAGAGCCC 
               
               
                   
                 GAGTGGAATCCAAGGATGGGTACTTTGACTACTGGGGCCAGGGAACCCTGGTCACCGTC 
               
               
                   
                 TCCTCA 
               
               
                   
               
               
                 SEQ ID 
                 GAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCCTGGGAGGTCCCTGAGACT 
               
               
                 132 
                 CTCCTGTGCAGCCTCTGGATTCACTTTCACTGATGCCTGGATGAACTGGGTCCGCCAGGC 
               
               
                   
                 TCCAGGGAAGGGGCTGGAGTGGATTGGCCGTGTTAAAAACAAAGCTGATGGTGAGACA 
               
               
                   
                 ACGGACTACGCTGCACCCGTCAAAGGCAGAATCACCATCTCAAGAGATGATGCAAAGA 
               
               
                   
                 ACACTCTGTATGTGCAAATGAACAGCCTGAAAACCGAGGACACAGCCGTGTATTATTGT 
               
               
                   
                 ACCGCTGACCTGCGACTTTCTACGTGGGATGCTTATGATTTCTGGGGCCAAGGGACAATG 
               
               
                   
                 GTCACCGTCTCTTCA 
               
               
                   
               
               
                 SEQ ID 
                 CAGATCACCTTGAAGGAGTCTGGGGGAGGCTTGGTCCAGCCTGGGGGGTCCCTAAGACT 
               
               
                 133 
                 CTCTTGTACAGTCTCAGGATTCACCTTTAGTAACAATTGGATGACCTGGGTCCGCCAGAC 
               
               
                   
                 TCCAGGGAAGGGGCTGGAGTGGGTGGCCAACATAAAGCAAGATGGAACTGAGAAACAC 
               
               
                   
                 TATGTGGACTCTGTGAAGGGCCGATTCACCATCTCCAGAGACAACGCCGAGAACTCACT 
               
               
                   
                 GTATCTGCAGATGAACAGCCTGAGAGGTGAGGACACGGCCGTGTATTATTGTGCGAGAA 
               
               
                   
                 ACAGTCAACGTTCGTTTGACTACTGGGGCCAGGGCACCCTGGTGACCGTCTCCTCA 
               
               
                   
               
               
                 SEQ ID 
                 CAGGTCACCTTGAAGGAGTCTGGGGGAGGCGTGGTCCAGCCTGGGAGGTCCCTGAGACT 
               
               
                 134 
                 CTCCTGTGCAGCCTCTGGATTCACCTTCAGTAGCTATGGCATGCACTGGGTCCGCCAGGC 
               
               
                   
                 TCCAGGCAAGGGGCTGGAGTGGGTGGCAGTTATATCATATGATGGAAGTAATAAATACT 
               
               
                   
                 ATGCAGACTCCGTGAAGGGCCGATTCACCATCTCCAGAGACAATTCCAAGAACACGCTG 
               
               
                   
                 TATCTGCAAATGAACAGCCTGAGAGCTGAGGACACGGCTGTGTATTACTGTGCGAAAGA 
               
               
                   
                 TTTAGGGGATCCCCGGGGTGGTATTTTGAACTACTGGGGCCAGGGCACCCTGGTCACCG 
               
               
                   
                 TCTCCTCA 
               
               
                   
               
               
                 SEQ ID 
                 GAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCCTGGGAGGTCCCTGAGACT 
               
               
                 135 
                 CTCCTGTGCAGCCTCTGGATTCACCTTCAGTAGCTATGCTATGCACTGGGTCCGCCAGGC 
               
               
                   
                 TCCAGGCAAGGGGCTGGAGTGGGTGGCAGTTATATCATATGATGGAAGTAATAAATACT 
               
               
                   
                 ACGCAGACTCCGTGAAGGGCCGATTCACCATCTCCAGAGACAATTCCAAGAACACGCTG 
               
               
                   
                 TATCTGCAAATGAACAGCCTGAGAGCTGAGGACACGGCTGTGTATTACTGTGCCCGGTC 
               
               
                   
                 GAGCCCCTGGGGGGAGTTATCGTTATACCAGGGGGCTTTTGATATCTGGGGCCAAGGGA 
               
               
                   
                 CAATGGTCACCGTCTCTTCA 
               
               
                   
               
               
                 SEQ ID 
                 CAGATCACCTTGAAGGAGTCTGGGGGAGGCTTGGTACAGCCTGGCAGGTCCCTGAGACT 
               
               
                 136 
                 CTCCTGTGCAGCCTCTGGATTCACCTTTGATGATTATGCCATGCACTGGGTCCGGCAAGC 
               
               
                   
                 TCCAGGGAAGGGGCTGGAGTGGGTCTCAGCTATTAGTGGTAGTGGTGGTAGCACATACT 
               
               
                   
                 ACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCAGAGACAATTCCAAGAACACGCTG 
               
               
                   
                 TATCTGCAAATGAACAGCCTGAGAGCCGAGGACACGGCCGTATATTACTGTGCGAAAGA 
               
               
                   
                 TAACGATTTTTGGAGTGGGAAAGTCTTTGACTACTGGGGCCAGGGCACCCTGGTCACCG 
               
               
                   
                 TCTCCTCA 
               
               
                   
               
               
                 SEQ ID 
                 GAAGTGCAGCTGGTGCAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGAGACT 
               
               
                 137 
                 CTCCTGTGCAGCCTCTGGATTCACCTTCAGTAGTTATAGCATGAACTGGGTCCGCCAGGC 
               
               
                   
                 TCCAGGGAAGGGGCTGGAGTGGGTTTCATACATCAGTAGTACTAGTAGTACCATATACT 
               
               
                   
                 ACGCAGACTCCGTGAAGGGCCGATTCACCATCTCCAGAGACAATTCCAAGAATATGCTG 
               
               
                   
                 TTTCTACAAATGAACAGCCTGAGAGCTGAGGACACGGCTGTGTATTACTGTGCGAAAGA 
               
               
                   
                 AGGGGGCAGTGGCTGGCGCCACTACTTTGACTACTGGGGCCAGGGAACCCTGGTCACCG 
               
               
                   
                 TCTCCTCA 
               
               
                   
               
               
                 SEQ ID 
                 CAGGTCACCTTGAAGGAGTCTGGGGGAGGCGTGGTCCAGCCTGGGAGGTCCCTGAGACT 
               
               
                 138 
                 GTCCTGTGCAGCCTCTGGATTCACCTTCAGCAGCTATGCTATGCACTGGGTCCGCCAGGC 
               
               
                   
                 TCCAGGCAAGGGGCTGGAGTGGGTGGCAGTTATATCATATGATGGAAGTAATAAATACT 
               
               
                   
                 ACGCAGACTCCGTGAAGGGCCGATTCACCATCTCCAGAGACAATTCCAAGAACACGCTG 
               
               
                   
                 TATCTGCAAATGAACAGCCTGAGAGCTGAGGACACGGCTGTGTATTACTGTGCGAGAGA 
               
               
                   
                 TTATTGTAGTAGTACCAGCTGCCAGAACTGGTTCGACCCCTGGGGCCAGGGCACCCTGG 
               
               
                   
                 TCACCGTCTCCTCA 
               
               
                   
               
               
                 SEQ ID 
                 CAGGTCCAGCTGGTGCAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGAGACT 
               
               
                 139 
                 CTCCTGTGCAGCCTCTGGATTCACCTTTAGCAACTATGTCATGAGCTGGGTCCGCCAGGC 
               
               
                   
                 TCCAGGGAAGGGGCTGGAGTGGGTCTCAGCTATTAGTGGTATTGGTGATACTACATACT 
               
               
                   
                 ACGCGGACTCCGTGAAGGGCCGATTCACCATCTCCAGAGACAACGCCAAGAACACGCTG 
               
               
                   
                 TATCTGCAAATGAACAGTCTGAGAGCCGAGGACACGGCTGTGTATTACTGTGCAAGAGG 
               
               
                   
                 GCGCGTGGCGGGGGATGCTTTTGATATCTGGGGCCAAGGGACAATGGTGACCGTCTCTT 
               
               
                   
                 CA 
               
               
                   
               
               
                 SEQ ID 
                 CAGCTGCAGCTGCAGGAGTCGGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGAGACT 
               
               
                 140 
                 CTCCTGTGCAGCCTCTGGATTCACCTTTAGCAGCTATGCCATGAGCTGGGTCCGCCAGGC 
               
               
                   
                 TCCAGGGAAGGGGCTGGAGTGGGTCTCAGCTATTAGTGGTAGTGGTGGTAGCACATACT 
               
               
                   
                 ACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCAGAGACAATTCCAAGAACACGCTG 
               
               
                   
                 TATCTGCAAATGAACAGCCTGAGAGCCGAGGACACGGCCGTATATTACTGTGCGAAAGA 
               
               
                   
                 TCAAGGGGCAGCAGCTGGTACCCTGGGGTACTTTGACTACTGGGGCCAGGGAACCCTGG 
               
               
                   
                 TGACCGTCTCCTCA 
               
               
                   
               
               
                 SEQ ID 
                 CAGGTGCAGCTGGTGCAGTCTGGGGCTGAGGTGAAGAAGCCTGGGGCCTCAGTGAAGGT 
               
               
                 141 
                 CTCCTGCAAGGCTTCTGGATACACCTTCACCAGTTATGATATCAACTGGGTGCGACAGGC 
               
               
                   
                 CACTGGACAAGGGCTTGAGTGGATGGGATGGATGAACCCTAACAGTGGTAACACAGGCT 
               
               
                   
                 ATGCACAGAAGTTCCAGGGCAGAGTCACCATGACCAGGAACACCTCCATAAGCACAGCC 
               
               
                   
                 TACATGGAGCTGAGCAGCCTGAGATCTGAGGACACGGCCGTGTATTACTGTACGAGAGG 
               
               
                   
                 AATCTATGATAGTAGTGGTTCTTCCAATCCCTTTGACTCCTGGGGCCAGGGAACCCTGGT 
               
               
                   
                 GACCGTCTCCTCA 
               
               
                   
               
               
                 SEQ ID 
                 GAGGTGCAGCTGGTGCAGTCTGGGGCTGAGGTGAAGAAGCCTGGGGCCTCAGTGAAGA 
               
               
                 142 
                 TTTCCTGCGAGGCTTCTGGATACACCTTCACTGATTATGCTATACATTGGGTGCGCCAGG 
               
               
                   
                 CCCCCGGACAAAGACTTGAGTGGATGGGATGGATCAACGCTGGCGATGGTGGCACAAA 
               
               
                   
                 AAGTTCACGGGAGTTCCAGGGCAGAGTCACCATTACCAGGGACACATCCGCGACCACAG 
               
               
                   
                 CCTACATGGAGGTGAGCAGTCTGAGATCTGAAGACACGGCTGTCTATTACTGTGCGAGA 
               
               
                   
                 GGATATTGTAGTGGTGGTAGCTGCCCAGGAACGGATTTTGACTACTGGGGCCAGGGAAC 
               
               
                   
                 CCTGGTCACCGTCTCCTCA 
               
               
                   
               
               
                 SEQ ID 
                 CAGGTGCAGCTGGTGCAGTCTGGGGCTGAGGTGAAGAAGCCTGGGGCCTCAGTGAAGGT 
               
               
                 143 
                 TTCCTGCAAGGCATCTGGATACACCTTCACCAGCTACTATATGCACTGGGTGCGACAGGC 
               
               
                   
                 CCCTGGACAAGGGCTTGAGTGGATGGGAATAATCAACCCTAGTGGTGGTAGCACAAGCT 
               
               
                   
                 ACGCACAGAAGTTCCAGGGCAGAGTCACCATGACCAGGGACACGTCCACGAGCACAGT 
               
               
                   
                 CTACATGGAGCTGAGCAGCCTGAGATCTGAGGACACGGCCGTGTATTACTGTGCGAGAG 
               
               
                   
                 ATGGTGTAGGAGGGAGAGATGGCTACAATTTTGACTACTGGGGCCAGGGAACCCTGGTC 
               
               
                   
                 ACCGTCTCCTCA 
               
               
                   
               
               
                 SEQ ID 
                 GAAGTGCAGCTGGTGCAGTCTGGGGGAGGCTTGGTCCAGCCTGGGGGGTCCCTGAGACT 
               
               
                 144 
                 CTCCTGTGCAGCCTCTGGATTCACCGTCAGTAGCAACTACATGAGCTGGGTCCGCCAGGC 
               
               
                   
                 TCCAGGGAAGGGGCTGGAGTGGGTCTCAGTTATTTATAGCGGTGGTAGCACATACTACG 
               
               
                   
                 CAGACTCCGTGAAGGGCCGATTCACCATCTCCAGAGACAATTCCAAGAACACGCTGTAT 
               
               
                   
                 CTTCAAATGAACAGCCTGAGAGCTGAGGACACGGCTGTGTATTACTGTGCGAGAGCCCC 
               
               
                   
                 CCTAGCAGCAGATGGCTACTTTGACTACTGGGGCCAGGGAACCCTGGTCACCGTCTCCTC 
               
               
                   
                 A 
               
               
                   
               
               
                 SEQ ID 
                 GAGGTCCAGCTGGTGCAGTCTGGGGCTGAGGTGAAGAAGCCTGGGTCCTCGGTGAAGGT 
               
               
                 145 
                 CTCCTGCAAGGCTTCTGGAGGCACCTTCAGCAGCTATGCTATCAGCTGGGTGCGACAGG 
               
               
                   
                 CCCCTGGACAAGGGCTTGAGTGGATGGGAGGGATCATCCCTATCTTTGGTACAGCAAAC 
               
               
                   
                 TACGCACAGAAGTTCCAGGGCAGAGTCACGATTACCGCGGACGAATCCACGAGCACAG 
               
               
                   
                 CCTACATGGAGCTGAGCAGCCTGAGATCTGAGGACACGGCCGTGTATTACTGTGCGAGA 
               
               
                   
                 GCCCGGGGGCTACAGTACCTAATCTGGTACTTCGATCTCTGGGGCCGTGGCACCCTGGTG 
               
               
                   
                 ACCGTCTCCTCA 
               
               
                   
               
               
                 SEQ ID 
                 CAGGTCCAGCTGGTACAGTCTGGGGCTGAGGTGAAGAAGCCTGGGGCCTCAGTGAAGGT 
               
               
                 146 
                 TTCCTGCAAGGCATCTGGATACACCTTCACCAGCTACTATATGCACTGGGTGCGACAGGC 
               
               
                   
                 CCCTGGACAAGGGCTTGAGTGGATGGGAATAATCAACCCTAGTGGTGGTAGCACAAGCT 
               
               
                   
                 ACGCACAGAAGTTCCAGGGCAGAGTCACCATGACCAGGGACACGTCCACGAGCACAGT 
               
               
                   
                 CTACATGGAGCTGAGCAGCCTGAGATCTGAGGACACGGCCGTGTATTACTGTGCGAGCC 
               
               
                   
                 CGGGTATGGTTCGGGGAGTTATTACTGCCCCGCTTGACTACTGGGGCCAGGGCACCCTG 
               
               
                   
                 GTCACCGTCTCCTCA 
               
               
                   
               
               
                 SEQ ID 
                 GAGGTCCAGCTGGTACAGTCTGGGGGAGGCCTGGTCAAGCCTGGGGGGTCCCTGAGACT 
               
               
                 147 
                 CTCCTGTGCAGCCTCTGGATTCACCTTCAGCAGCTATGCTATCAGCTGGGTGCGACAGGC 
               
               
                   
                 CCCTGGACAAGGGCTTGAGTGGATGGGAGGGATCATCCCTATGTATGGTACAGCAAACT 
               
               
                   
                 ACGCACAGAAGTTCCAGGGCAGAGTCACGATTACCGCGGACGAATCCACGAGCACAGC 
               
               
                   
                 CTACATGGAACTGAGCAGCCTGAGATCTGAGGACACGGCCCTCTATTACTGTGCGAGAG 
               
               
                   
                 AAGCTAAGTGGGGAATGTACTACTTTGACTACTGGGGCCAGGGCACCCTGGTCACCGTC 
               
               
                   
                 TCCTCA 
               
               
                   
               
               
                 SEQ ID 
                 GAGGTGCAGCTGGTGGAGTCCGGGGGAGGCGTGGTCCAGCCTGGGAGGTCCCTGAGACT 
               
               
                 148 
                 CTCCTGTGCAGCCTCTGGATTCACCTTCAGTAGCTATGCTATACACTGGGTCCGCCAGGC 
               
               
                   
                 TCCAGGCAAGGGGCTGGAGTGGGTGGCAATTATATCAGATGATGGAAGTAAGAGTTACT 
               
               
                   
                 ACGCAGACTCCGTGCAGGGCCGATTCACCATCTCCAGAGACAATTCGAGGAACACAGTA 
               
               
                   
                 TATCTGCAAATGAACAGCCTGAGAGCTGAGGACACGGCTATGTATTACTGTGCGAGAGA 
               
               
                   
                 CAGGGGAACTAAATGGAACCAATTGAATGATGTTTTTGATATGTGGGGCCAAGGGACAA 
               
               
                   
                 TGGTCACCGTCTCTTCA 
               
               
                   
               
               
                 SEQ ID 
                 CAGATGCAGCTGGTGCAATCTGGGGCTGAGGTGAAGAAGCCTGGGGCCTCAGTGAAGGT 
               
               
                 149 
                 CTCCTGCACGGCTTCTGGATACACCTTCACCAGTTCTGATATCAACTGGGTGCGACAGGC 
               
               
                   
                 CACTGGACAAGGGCTTGAGTGGATGGGATGGATGAACCCTAACAGTGGTAACACCGGCT 
               
               
                   
                 ATGCAGAGAAGTTCCAGGGCAGGGTCACCATGACCAGCGACTCCTCCATAAGCACCGCC 
               
               
                   
                 TACATGGAGTTGAGAAGCCTGACCACTGAGGACACGGCCGTATATTACTGTGCGAGAGG 
               
               
                   
                 TGGGGGTGCGAGCTATACTGACTCCTGGGGCCAGGGCACCCTGGTCACCGTCTCCTCA 
               
               
                   
               
               
                 SEQ ID 
                 CAGGTCCAGCTGGTGCAGTCTGGGGGAGGCTTGGTACAGCCAGGGCGGTCCCTGAGACT 
               
               
                 150 
                 CTCCTGTACAGCTTCTGGATTCACCTTTGGTGATTATGCTATGAGCTGGTTCCGCCAGGC 
               
               
                   
                 TCCAGGGAAGGGGCTGGAGTGGGTAGGTTTCATTAGAAGCAAAGCTTATGGTGGGACAA 
               
               
                   
                 CAGAATACGCCGCGTCTGTGAAAGGCAGATTCACCATCTCAAGAGATGATTCCAAAAGC 
               
               
                   
                 ATCGCCTATCTGCAAATGAACAGCCTGAAAACCGAGGACACAGCCGTGTATTACTGTAC 
               
               
                   
                 CGCTAAGGGGGGCTACGTCGGATACAGCTATGGACCTTTTGGGGGCTACTGGGGCCAGG 
               
               
                   
                 GAACCCTGGTCACCGTCTCCTCA 
               
               
                   
               
               
                 SEQ ID 
                 CAGGTGCAGCTGGTGCAGTCTGGGGGAGGCTTGGTACAGCCAGGGCGGTCCCTGAGACT 
               
               
                 151 
                 CTCCTGTACAGCTTCTGGATTCACCTTTGGTGATTATGCTATGAGCTGGTTCCGCCAGGC 
               
               
                   
                 TCCAGGGAAGGGGCTGGAGTGGGTAGGTTTCATTAGAAGCAAAGCTTATGGTGGGACAA 
               
               
                   
                 CAGAATACGCCGCGTCTGTGAAAGGCAGATTCACCATCTCAAGAGATGATTCCAAAAGC 
               
               
                   
                 ATCGCCTATCTGCAAATGAACAGCCTGAAAACCGAGGACACAGCCGTGTATTACTGTAC 
               
               
                   
                 TAGAGGGGGGACTATGGTTCGGGGTTTCGGATTTAACTACTGGGGCCAGGGAACCCTGG 
               
               
                   
                 TCACCGTCTCCTCA 
               
               
                   
               
               
                 SEQ ID 
                 CAGGTGCAGCTACAGCAGTGGGGCGCAGGACTGTTGAAGCCTTCGGAGACCCTGTCCCT 
               
               
                 152 
                 CACCTGCGCTGTCTATGGTGGGTCCTTCAGTGGTTACTACTGGAGCTGGATCCGCCAGCC 
               
               
                   
                 CCCAGGGAAGGGGCTGGAGTGGATTGGGGAAATCAATCATAGTGGAAGCACCAACTAC 
               
               
                   
                 AACCCGTCCCTCAAGAGTCGAGTCACCATATCAGTAGACACGTCCAAGAACCAGTTCTC 
               
               
                   
                 CCTGAAGCTGAGCTCTGTGACCGCCGCGGACACGGCTGTGTATTACTGTGCGAGAGCCC 
               
               
                   
                 GGCGGGCTATGATAGGGCCGCTTCCGCGACTTGTCGGGTACTTCGATCTCTGGGGCCGTG 
               
               
                   
                 GAACCCTGGTCACCGTCTCCTCA 
               
               
                   
               
               
                 SEQ ID 
                 CAGGTGCAGCTACAGCAGTGGGGCGCAGGACTGTTGAAGCCTTCGGAGACCCTGTCCCT 
               
               
                 153 
                 CACCTGCGCTGTCTATGGTGGGTCCTTCAGTGGTTACTACTGGAGCTGGATCCGCCAGCC 
               
               
                   
                 CCCAGGGAAGGGGCTGGAGTGGATTGGGGAAATCAATCATAGTGGAAGCACCAACTAC 
               
               
                   
                 AACCCGTCCCTCAAGAGTCGAGTCACCATATCAGTAGACACGTCCAAGAACCAGTTCTC 
               
               
                   
                 CCTGAAGCTGAGCTCTGTGACCGCCGCGGACACGGCTGTGTATTACTGTGCGAGAGGCC 
               
               
                   
                 GCCCCGCCCCATCCTGGGTTAAAACCCGTAACTGGTTCGACCCCTGGGGCCAGGGAACC 
               
               
                   
                 CTGGTCACCGTCTCCTCA 
               
               
                   
               
               
                 SEQ ID 
                 CAGGTACAGCTGCAGCAGTCAGGTCCAGGACTGGTGAAGCCCTCGCAGACCCTCTCACT 
               
               
                 154 
                 CACCTGTGCCATCTCCGGGGACAGTGTCTCTAGCAACAGTGCTGCTTGGAACTGGATCA 
               
               
                   
                 GGCAGTCCCCATCGAGAGGCCTTGAGTGGCTGGGAAGGACATACTACAGGTCCAAGTGG 
               
               
                   
                 TATAATGATTATGCAGTATCTGTGAAAAGTCGAATAACCATCAACCCAGACACATCCAA 
               
               
                   
                 GAACCAGTTCTCCCTGCAGCTGAACTCTGTGACTCCCGAGGACACGGCTGTGTATTACTG 
               
               
                   
                 TGCAAGAGAGGCTAGCAGTGGCTGGAACTGGGGCCAGGGAACCCTGGTCACCGTCTCCT 
               
               
                   
                 CA 
               
               
                   
               
               
                 SEQ ID 
                 CAGGTGCAGCTGCAGGAGTCCGGTCCAGGACTGGTGAAGCCCTCGCAGACCCTCTCACT 
               
               
                 155 
                 CACCTGTGCCATCTCCGGGGACAGTGTCTCTAGCAACAATGCTGCTTGGAACTGGATCA 
               
               
                   
                 GGCAGTCCCCATCGAGAGGCCTTGAGTGGCTGGGAAGGACATTCTACAGGTCCAAGTGG 
               
               
                   
                 TATAATGACTATGCAGTTTCTGTGAAAAGTCGACTAACCGTCAACCCAGACACATCCAA 
               
               
                   
                 GAACCAGTTCTCCCTGCGGTTGAACTCTGTGAGTCCCGAGGACACGGCTGTGTATTACTG 
               
               
                   
                 TGCAAGAGGGGGAAGATATACCAAGGGAGGGTACTTTGACGACTGGGGCCAGGGAACC 
               
               
                   
                 CTGGTGACCGTCTCCTCA 
               
               
                   
               
               
                 SEQ ID 
                 CAGGTCACCTTGAAGGAGTCTGGTCCTACGCTGGTGAAACCCACACAGACCCTCACGCT 
               
               
                 156 
                 GACCTGCACCTTCTCTGGGTTCTCACTCAGCACTAGTGGAGTGGGTGTGGGCTGGATCCG 
               
               
                   
                 TCAGCCCCCAGGAAAGGCCCTGGAGTGGCTTGCACTCATTTATTGGGATGATGATAAGC 
               
               
                   
                 GCTACAGCCCATCTCTGAAGAGCAGGCTCACCATCACCAAGGACACCTCCAAAAACCAG 
               
               
                   
                 GTGGTCCTTACAATGACCAACATGGACCCTGTGGACACAGCCACATATTACTGTGCACA 
               
               
                   
                 CAGATTGGATAGCAGTGGCCGTGGTGGTTACTTTGACTACTGGGGCCAGGGCACCCTGG 
               
               
                   
                 TCACCGTCTCCTCA 
               
               
                   
               
               
                 SEQ ID 
                 GAGGTGCAGCTGGTGGAGTCTGGGGGAGGCGTGGTCCAGCCTGGGAGGTCCCTGAGACT 
               
               
                 157 
                 CTCCTGTACAGCCTCTGGATTCACCTTCAGTAGCTATGGCATGCACTGGGTCCGCCAGGC 
               
               
                   
                 TCCAGGCAAGGGGCTGGAGTGGGTGGCAGTTATATCATATGATGGAAGTAATAAATACT 
               
               
                   
                 ATGCAGACTCCGTGAAGGGCCGATTCACCATCTCCAGAGACAATTCCAAGAACACGCTG 
               
               
                   
                 TATCTGCAAATGAACAGCCTGAGAGCTGAGGACACGGCTGTGTATTACTGTGCGAAAGA 
               
               
                   
                 GTTGGTGGGTACCAGCTCTCCTTATTACTACTACTACTACGGTATGGACGTCTGGGGCCA 
               
               
                   
                 AGGGACAATGGTCACCGTCTCTTCA 
               
               
                   
               
               
                 SEQ ID 
                 CAGCTGCAGCTGCAGGAGTCGGGGGGAGGCTTGGTCCAGCCTGGGGGGTCCCTGAGACT 
               
               
                 158 
                 CTCCTGTGCAGCCTCTGGATTCACCGTCAGTAGCAACTACATGAGCTGGGTCCGCCAGGC 
               
               
                   
                 TCCAGGGAAGGGGCTGGAGTGGGTCTCAGTTATTTATAGCGGTGGTAGCACATACTACG 
               
               
                   
                 CAGACTCCGTGAAGGGCAGATTCACCATCTCCAGAGACAATTCCAAGAACACGCTGTAT 
               
               
                   
                 CTTCAAATGAACAGCCTGAGAGCCGAGGACACGGCTGTGTATTACTGTGCGAGAGACTA 
               
               
                   
                 TTACTATGGTTCGGGGAGTTCTCCCTGGGGCCAGGGAACCCTGGTCACCGTCTCCTCA 
               
               
                   
               
               
                 SEQ ID 
                 CAGGTGCAGCTACAGCAGTGGGGCGCAGGACTGTTGAAGCCTTCGGAGACCCTGTCCCT 
               
               
                 159 
                 CACCTGCGCTGTCTATGGTGGGTCCTTCAGTGGTTACTACTGGAGCTGGATCCGCCAGCC 
               
               
                   
                 CCCAGGGAAGGGGCTGGAGTGGATTGGGGAAATCAATCATAGTGGAAGCACCAACTAC 
               
               
                   
                 AACCCGTCCCTCAAGAGTCGAGTCACCATATCAGTAGACACGTCCAAGAACCAGTTCTC 
               
               
                   
                 CCTGAAGCTGAGCTCTGTGACCGCCGCGGACACGGCTGTGTATTACTGTGCGAGAGGCC 
               
               
                   
                 GGCCATATTGTAGTAGTACCAGCTGCTACCCAGAGTGGTTCGACCCCTGGGGCCAGGGA 
               
               
                   
                 ACCCTGGTCACCGTCTCCTCA 
               
               
                   
               
               
                 SEQ ID 
                 CAGGTCACCTTGAAGGAGTCTGGGGGAGGCGTGGTCCAGCCTGGGAGGTCCCTGAGACT 
               
               
                 160 
                 CTCCTGTGCAGCCTCTGGATTCACCTTCAGTAGCTATGGCATGCACTGGGTCCGCCAGGC 
               
               
                   
                 TCCAGGCAAGGGGCTGGAGTGGGTGGCAGTTATATCATATGATGGAAGTAATAAATACT 
               
               
                   
                 ATGCAGACTCCGTGAAGGGCCGATTCACCATCTCCAGAGACAATTCCAAGAACACGCTG 
               
               
                   
                 TATCTGCAAATGAACAGCCTGAGAGCTGAGGACACGGCTGTGTATTACTGTGCGAAATT 
               
               
                   
                 AAGGGGTATAGATTACTATGATAGTAGTGGTTACCAACGGGGGTTTGACTACTGGGGCC 
               
               
                   
                 AGGGAACCCTGGTCACCGTCTCCTCA 
               
               
                   
               
               
                 SEQ ID 
                 CAGGTGCAGCTGCAGGAGTCCGGCCCAGGACTGGTGAAGCCTTCGGAGACCCTGTCCCT 
               
               
                 161 
                 CACCTGCACTGTCTCTGGTGGCTCCATCAGTAGTTACTACTGGAGCTGGATCCGGCAGCC 
               
               
                   
                 CCCAGGGAAGGGACTGGAGTGGATTGGCTATATCTATTACACTGGGAGCACCAACTACA 
               
               
                   
                 ACCCCTCCCTCAAGAGCCGAGTCACCATATCAGTAGACACGTCCAAGAACCAGTTCTCC 
               
               
                   
                 CTGAAGCTGAGCTCTGTGACCACTGCGGACACGGCCGTGTATTACTGTGCGAGAGGTGG 
               
               
                   
                 GAGGGGGGATGGGGCCGCTTTTGACATCTGGGGCCAAGGGACAATGGTCACCGTCTCTT 
               
               
                   
                 CA 
               
               
                   
               
               
                 SEQ ID 
                 CAGGTGCAGCTGGTGCAATCTGGGGGAGGCGTGGTCCAGCCTGGGAGGTCCCTGAGACT 
               
               
                 162 
                 CTCCTGTGCAGCGTCTGGATTCACCTTCAGCAGCTCTGCCATGCACTGGGTCCGCCAGGC 
               
               
                   
                 TCCAGGCAAGGGACTGGAGTGGGTGGCAATGATTTGGCATGATGAGAGTAAGAAATACT 
               
               
                   
                 ATGCAGACTCCGTGAAGGGCCGATTCACTATCTCCAGAGACAATTCCAAGAACACGCTG 
               
               
                   
                 TATCTGCAAATGAACAGCCTGAGAGCTGAGGACACGGCTGTGTATTACTGTGCGAGACC 
               
               
                   
                 CCCCGACGGTGGTAACTCCGGTCGCTGGTACTTCGATCTCTGGGGCCGTGGCACCCTGGT 
               
               
                   
                 CACCGTCTCCTCA 
               
               
                   
               
               
                 SEQ ID 
                 CAGATGCAGCTGGTGCAATCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGAGACT 
               
               
                 163 
                 CTCCTGTGCAGCCTCTGGATTCACCTTTAGCAGCTATGCCATGAGCTGGGTCCGCCAGGC 
               
               
                   
                 TCCAGGGAAGGGGCTGGAGTGGGTCTCAGCTATTAGTGGTAGTGGTGGTAGCACATACT 
               
               
                   
                 ACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCAGAGACAATTCCAAGAACACGCTG 
               
               
                   
                 TATCTGCAAATGAACAGCCTGAGAGCCGAGGACACGGCCGTATATTACTGTGCGAAAGA 
               
               
                   
                 CAAGAACGTCCGAAAACATGACTACGGTGACCACCCCTACGGGGGGTACTTTGACTACT 
               
               
                   
                 GGGGCCAGGGCACCCTGGTGACCGTCTCCTCA 
               
               
                   
               
               
                 SEQ ID 
                 GAGGTCCAGCTGGTACAGTCTGGGGCTGAGGTGAAGAAGCCTGGGGCCTCAGTGAAGGT 
               
               
                 164 
                 TTCCTGCAAGGCTTCTGGATACACCTTCACTAGCTATGCTATGCATTGGGTGCGCCAGGC 
               
               
                   
                 CCCCGGACAAAGGCTTGAGTGGATGGGATGGATCAACGCTGGCAATGGTAACACAAAA 
               
               
                   
                 TATTCACAGAAGTTCCAGGGCAGAGTCACCATTACCAGGGACACATCCGCGAGCACAGC 
               
               
                   
                 CTACATGGAGCTGAGCAGCCTGAGATCTGAAGACACGGCTGTGTATTACTGTGCGAGAG 
               
               
                   
                 TGGCGGGAGCTACTTCCCTATGGTACTGGGGCCAGGGCACCCTGGTCACCGTCTCCTCA 
               
               
                   
               
               
                 SEQ ID 
                 CAGGTACAGCTGCAGCAGTCAGGTCCAGGACTGGTGAAGCCCTCGCAGAGCCTCTCACT 
               
               
                 165 
                 CACCTGTGCCATCTCCGGGGACAGTGTCTCTAGCAACAGTGCTGCTTGGAACTGGATCA 
               
               
                   
                 GGCAGTCCCCATCGAGAGGCCTTGAGTGGCTGGGAAGGACATACTACAGGTCCAAGTGG 
               
               
                   
                 TATAATGATTATGCAGTATCTGTGAAGAGTCGAATAACCATCAAACCAGACACATCCAA 
               
               
                   
                 GAACCAGTTCTCCCTGCAGCTGAACTCTGTGACTCCCGAGGACACGGCTGTGTATTACTG 
               
               
                   
                 TACAAGGCTAGCTAATTCCGACGGTGTGGACGTCTGGGGCCAAGGGACAATGGTCACCG 
               
               
                   
                 TCTCCTCA 
               
               
                   
               
               
                 SEQ ID 
                 CAGGTACAGCTGCAGCAGTCAGGTCCAGGACTGGTGAAGCCCTCGCAGACCCTCTCACT 
               
               
                 166 
                 CACCTGTGCCATCTCCGGGGACAGTGTCTCTAGCGACAGTGCTGTTTGGACCTGGATCAG 
               
               
                   
                 GCAGTCCCCATCGAGAGGCCTTGAGTGGCTGGGAAGGACATACTACAAGTCGAAGTGGT 
               
               
                   
                 ATAATGATTATGCAGCATCTGTGAAAAGTCGAATAACCATCAACCCAGACACATCCAAG 
               
               
                   
                 AACCAGTTCTCCCTGCACCTGAACTCTGTGACTCCCGAGGACACGGCTGTGTATTACTGT 
               
               
                   
                 GCAAGAGGTGTAACCCGGACCTTTGACTACTGGGGCCAGGGGACCACGGTCACCGTCTC 
               
               
                   
                 CTCA 
               
               
                   
               
               
                 SEQ ID 
                 CAGCTGCAGCTGCAGGAGTCGGGTCCAGGACTGGTGAAGCCCTCGCAGACCCTCTCACT 
               
               
                 167 
                 CACCTGTGCCATCTCCGGGGACAGTGTCTCTAGCAACAGTGCTGCTTGGAACTGGATCA 
               
               
                   
                 GGCAGTCCCCATCGAGAGGCCTTGAGTGGCTGGGAAGGACATACTACAGGTCCAAGTGG 
               
               
                   
                 TATAATGATTATGCAGTATCTGTGAAAAGTCGAATAACCATCAACCCAGACACATCCAA 
               
               
                   
                 GAACCAGTTCTCCCTGCAGCTGAACTCTGTGACTCCCGAGGACACGGCTGTGTATTACTG 
               
               
                   
                 TGCAGAAGGCAATGGGCCGTTCGACCCCTGGGGCCAGGGAACCCTGGTGACCGTCTCCT 
               
               
                   
                 CA 
               
               
                   
               
               
                 SEQ ID 
                 CAGATCACCTTGAAGGAGTCTGGGGGAGGCGTGGTCCAGCCTGGGAGGTCCCTGAGACT 
               
               
                 168 
                 CTCCTGTGTAGCCTCTGGATTCACCTTCAGTACCTATCCCATGCACTGGGTCCGCCAGGC 
               
               
                   
                 TCCAGGCAAGGGGCTGGAGTGGGTGGCAGTTATATCATATGATGGACGTAATGAATACT 
               
               
                   
                 ACGCAGACTCCGTGAAGGGCCGATTCACCATCTCCAGAGACAATTCCAAAAACACGCTG 
               
               
                   
                 TATCTGCAAATGAACAGTCTGCGAGCTGAAGACACGGCTGTCTATTATTGTGCGACTCG 
               
               
                   
                 GGATACACCTTTGGTTGGGGTTTCGATATACTGGGGCCAGGGCACCCTGGTCACCGTCTC 
               
               
                   
                 CTCA 
               
               
                   
               
               
                 SEQ ID 
                 CAGATGCAGCTGGTGCAATCTGGGGGAGGCCTGGTCAAGGCTGGGGGGTCCCTGAGACT 
               
               
                 169 
                 CTCCTGTTCAGCCTCTGGATTCACCTTCAGTAGCTATGCTATGCACTGGGTCCGCCAGGC 
               
               
                   
                 TCCAGGGAAGGGACTGGAATATGTTTCAGCTATTAGTAGTAATGGGGGTAGCACATACT 
               
               
                   
                 ACGCAGACTCAGTGAAGGGCAGATTCACCATCTCCAGAGACAATTCCAAGAACACGCTG 
               
               
                   
                 TATCTTCAAATGAGCAGTCTGAGAGCTGAGGACACGGCTGTGTATTACTGTGTGAATCG 
               
               
                   
                 GGCGGGTTACGGTGACTACAGACACTTCCAGCACTGGGGCCAGGGCACCCTGGTCACCG 
               
               
                   
                 TCTCCTCA 
               
               
                   
               
               
                 SEQ ID 
                 GAGGTGCAGCTGGTGCAGTCTGGGGGAGGCGTGGTCCAGCCTGGGGGGTCCCTGAGACT 
               
               
                 170 
                 CTCCTGTGCAGCGTCTGGATTCACCTTCAGTAGCTATGGCATGCACTGGGTCCGCCAGGC 
               
               
                   
                 TCCAGGCAAGGGGCTGGAGTGGGTGGCATTTATATCATATGATGGAAGTAATAAATACT 
               
               
                   
                 ACGCAGACTCCGTGAAGGGCCGATTCACCATCTCCAGAGACAATTCCAAGAACACGCTG 
               
               
                   
                 TATCTGCAAATGAACAGCCTGAGAGCCGAGGACACGGCCGTATATTACTGTGCGACAAC 
               
               
                   
                 AGGGGACCGCTTCCAAGAGTTTGACTACTGGGGCCAGGGAACCCTGGTCACCGTCTCCT 
               
               
                   
                 CA 
               
               
                   
               
               
                 SEQ ID 
                 CAGATGCAGCTGGTGCAGTCTGGGGGAGTCTTGCTTCAGCCAGGGCGGTCCCTGAGACT 
               
               
                 171 
                 CTCCTGTACAGCTTCTGGATTCACCTTTGCTGCTTATAATATCAACTGGTTCCGCCAGGGT 
               
               
                   
                 CCTGGGGGGGGGCTGGAGTGGGTAGGTTTCATTAGAGCCAACGCTGATAGTGGGACAAC 
               
               
                   
                 AGAGTACGCCGCGTCTGTGAAAGGCAGATTCTTCATCTCAAGAGATGATTCCAGAAGCA 
               
               
                   
                 CCGCCTACCTGCAAATGACTAGCCTTAAAACCGAGGACACAGCCGTTTATTACTGTGCC 
               
               
                   
                 AGAGATGATCGGGGTCGGGGAGATGACTTTGACTACTGGGGCCAGGGCACCCTGGTCAC 
               
               
                   
                 CGTCTCCTCA 
               
               
                   
               
               
                 SEQ ID 
                 CAGGTGCAGCTGGTGCAATCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGAGACT 
               
               
                 172 
                 CTCCTGTGCAGCCTCTGGATTCACCTTTAGCAGCTATGGCATGACGTGGGTCCGCCAGGC 
               
               
                   
                 TCCAGGGAAGGGGCTGGAGTGGGTCTCAACTATTAGTGGTAATGGTGTTGGCACATACT 
               
               
                   
                 ACCCAGACTCCGTGAAGGACCGGTTCACCATCTCCAGAGACAGTTCCAAGAACACGGTG 
               
               
                   
                 TATCTGCAAATGAACAGCCTGAGAGCCGAGGACACGGCCGTATATTACTGTGTGAAACA 
               
               
                   
                 TGGTAGGGCCGGAATAAACTGGTACTTCGATCTCTGGGGCCGTGGCACCCTGGTGACCG 
               
               
                   
                 TCTCCTCA 
               
               
                   
               
               
                 SEQ ID 
                 CAGGTACAGCTGCAGCAGTCAGGTCCAGGACTGGTGAAGCCCTCGCAGACCCTCTCACT 
               
               
                 173 
                 CACCTGTGCCATCTCCGGGGACAGTGTCTCTAGCAACAGTGCTGCTTGGAACTGGATCA 
               
               
                   
                 GGCAGTCCCCATCGAGAGGCCTTGAGTGGCTGGGAAGGACATACTACAGGTCCAAGTGG 
               
               
                   
                 TATAATGATTATGCAGTATCTGTGAAAAGTCGAATAACCATCAACCCAGACACATCCAA 
               
               
                   
                 GAACCAGTTCTCCCTGCAGCTGAACTCTGTGACTCCCGAGGACACGGCTGTGTATTACTG 
               
               
                   
                 TGCAAGAGGGGGAGGGCTTTGGGCTTTTGATATCTGGGGCCAAGGGACCACGGTCACCG 
               
               
                   
                 TCTCCTCA 
               
               
                   
               
               
                 SEQ ID 
                 GAGGTCCAGCTGGTGCAGTCTGGGGCTGAGGTGAAGAAGCCTGGGGCCTCAGTGAAGGT 
               
               
                 174 
                 CTCCTGCAAGGCTTCTGGATACACCTTCACCGGCTACTATATGCACTGGGTGCGACAGGC 
               
               
                   
                 CCCTGGACAAGGGCTTGAGTGGATGGGATGGATCAACCCTAACAGTGGTGGCACAAACT 
               
               
                   
                 ATGCACAGAAGTTTCAGGGCAGGGTCACCATGACCAGGGACACGTCCATCAGCACAGCC 
               
               
                   
                 TACATGGAGCTGAGCAGGCTGAGATCTGACGACACGGCCGTGTATTACTGTGCGAGAGA 
               
               
                   
                 CAAGATCGGCAGCTGTCCTTACTGGGGCCAGGGAACCCTGGTCACCGTCTCCTCA 
               
               
                   
               
               
                 SEQ ID 
                 CAGGTCACCTTGAAGGAGTCTGGTCCTACGCTGGTGAAACCCACACAGACCCTCACGCT 
               
               
                 175 
                 GACCTGCACCTTCTCTGGGTTCTCACTCAGCACTAGTGGAGTGGGTGTGGGCTGGATCCG 
               
               
                   
                 TCAGCCCCCAGGAAAGGCCCTGGAGTGGCTTGCACTCATTTATTGGGATGATGATAAGC 
               
               
                   
                 GCTACAGCCCATCTCTGAAGAGCAGGCTCACCATCACCAAGGACACCTCCAAAAACCAG 
               
               
                   
                 GTGGTCCTTACAATGACCAACATGGACCCTGTGGACACAGCCACATATTACTGTGCACA 
               
               
                   
                 CAGACCGGATAGCAGCAGTCAATGTTTTGACTACTGGGGCCAGGGAACCCTGGTCACCG 
               
               
                   
                 TCTCCTCA 
               
               
                   
               
               
                 SEQ ID 
                 CAGGTCACCTTGAAGGAGTCTGGGGGAGGCGTGGTCCAGCCTGGGAGGTCCCTGAGACT 
               
               
                 176 
                 CTCCTGTGCAGCCTCTGGATTCACCTTCAGTAGCTATGCTATGCACTGGGTCCGCCAGGC 
               
               
                   
                 TCCAGGCAAGGGGCTGGAGTGGGTGGCAGTTATATCATATGATGGAAGTAATAAATACT 
               
               
                   
                 ACGCAGACTCCGTGAAGGGCCGATTCACCATCTCCAGAGACAATTCCAAGAACACGCTG 
               
               
                   
                 TATCTGCAAATGAACAGCCTGAGAGCTGAGGACACGGCTGTGTATTACTGTGCGAGAAG 
               
               
                   
                 CAGTGGCTGGTCACTGCCTGAAGACTACTGGGGCCAGGGAACCCTGGTCACCGTCTCCT 
               
               
                   
                 CA 
               
               
                   
               
               
                 SEQ ID 
                 CAGGTCCAGCTGGTACAGTCTGGGGCTGAGGTGAAGAAGCCTGGGGCCTCAGTGAAGGT 
               
               
                 177 
                 CTCCTGCAAGGTTTCCGGATACACCCTCACTGAATTATCCATGCACTGGGTGCGACAGGC 
               
               
                   
                 TCCTGGAAAAGGGCTTGAGTGGATGGGAGGTTTTGATCCTGAAGATGGTGAAACAATCT 
               
               
                   
                 ACGCACAGAAGTTCCAGGGCAGAGTCACCATGACCGAGGACACATCTACAGACACAGC 
               
               
                   
                 CTACATGGAGCTGAGCAGCCTGAGATCTGAGGACACGGCCGTGTATTACTGTGCAACGG 
               
               
                   
                 ATGTGAACCCGGAGCTACTGGGGGCGGGATTTGACTACTGGGGCCAGGGCACCCTGGTC 
               
               
                   
                 ACCGTCTCCTCA 
               
               
                   
               
               
                 SEQ ID 
                 CAGGTCACCTTGAAGGAGTCTGGGGGAGGCTTGGTCCAGCCTGGAGGGTCCCTGAGACT 
               
               
                 178 
                 CTCCTGTGCAGCCTCTGGATTCACCTTCAGTGACCAGTACATGGACTGGGTCCGCCAGGC 
               
               
                   
                 TCCAGGGAAGGGGCTGGAGTGGGTTGGCCGTGTTAGAAACAAAGCTAACAGTTACACCA 
               
               
                   
                 CAGAATACGCCGCGTCTGTGAAAGGCAGATTCACCATCTCAAGAGATGATTCAAAGAAC 
               
               
                   
                 TCACTGTATCTGCAAATGAATAGTCTGAACACCGAGGACACGGCCATGTATTTCTGTGCT 
               
               
                   
                 AGTAGTCTCAATAGTGGGGGCTACCGATGCTTCCATCACTGGGGCCAGGGCACCCTGGT 
               
               
                   
                 GACCGTCTCCTCA 
               
               
                   
               
               
                 SEQ ID 
                 CAGGTCCAGCTGGTGCAGTCTGGGGGAGGCTTGGTCCAGCCTGGGGGGTCCCTGAGACT 
               
               
                 179 
                 CTCCTGTTCAGCCTCTGGATTCACCTTCAGTAGCTATGCTATGCACTGGGTCCGCCAGGC 
               
               
                   
                 TCCAGGGAAGGGACTGGAATATGTTTCAGCTATTAGTAGTAATGGGGGTAGCACATACT 
               
               
                   
                 ACGCAGACTCAGTGAAGGGCAGATTCACCATCTCCAGAGACAATTCCAAGAACACGCTG 
               
               
                   
                 TATCTTCAAATGAGCAGTCTGAGAGCTGAGGACACGGCTGTGTATTACTGTGTGAAAGC 
               
               
                   
                 GCCGAGGGGTGTAGTACCAGCTGCTATGCGGGGGGGCTACTGGGGCCAGGGAACCCTG 
               
               
                   
                 GTCACCGTCTCCTCA 
               
               
                   
               
               
                 SEQ ID 
                 CAGGTGCAGCTGCAGGAGTCGGGGGGAGGCTTGGTACAGCCAGGGCGGTCCCTGAGAC 
               
               
                 180 
                 TCTCCTGTACAGCTTCTGGATTCACCTTTGGTGATTATGCTATGAGCTGGTTCCGCCAGG 
               
               
                   
                 CTCCAGGGAAGGGGCTGGAGTGGGTAGGTTTCATTAGAAGCAAAGCTTATGGTGGGACA 
               
               
                   
                 ACAGAATACGCCGCGTCTGTGAAAGGCAGATTCACCATCTCAAGAGATGATTCCAAAAG 
               
               
                   
                 CATCGCCTATCTGCAAATGAACAGCCTGAAAACCGAGGACACAGCCGTGTATTACTGTA 
               
               
                   
                 CTAGATTGGTGGGCAATAGTGGGAGCTACTATCCGTTTGGGTACTGGGGCCAGGGAACC 
               
               
                   
                 CTGGTGACCGTCTCCTCA 
               
               
                   
               
               
                 SEQ ID 
                 CAGGTGCAGCTACAGCAGTGGGGCGCAGGACTGTTGAAGCCTTCGGAGACCCTGTCCCT 
               
               
                 181 
                 CACCTGCGCTGTCTATGGTGGGTCCTTCAGTGGTTACTACTGGAGCTGGATCCGCCAGCC 
               
               
                   
                 CCCAGGGAAGGGGCTGGAGTGGATTGGGGAAATCAATCATAGTGGAAGCACCAACTAC 
               
               
                   
                 AACCCGTCCCTCAAGAGTCGAGTCACCATATCAGTAGACACGTCCAAGAACCAGTTCTC 
               
               
                   
                 CCTGAAGCTGAGCTCGGTGACCGCCGCGGACACGGCTGTGTATTACTGTGCGAGAGGCC 
               
               
                   
                 GGTCCCTTCCCTACCGGGGGTTGGCTCCTAGATCTTTCGGAGGATACTACTTTGACTACT 
               
               
                   
                 GGGGCCAGGGAACCCTGGTCACCGTCTCCTCA 
               
               
                   
               
               
                 SEQ ID 
                 CAGGTGCAGCTGCAGGAGTCGGGGGGAGGCTTGGTACGGCCTGGAGGGTCCCTGAGACT 
               
               
                 182 
                 CTCCTGTGGAGACTCTGGATTCAACTTCAGTGGATATGAAATGAACTGGGTCCGCCAGG 
               
               
                   
                 CTCCAGGGAAGGGGCTGGAGTGGGTTTCATACGTCAGTACTAGTGGTAGTACCAGATAC 
               
               
                   
                 TACGCAGACTCTGTGAAGGGCCGATTTACCATCTCCAGAGACAACGCCAAGAACACCCT 
               
               
                   
                 GTATTTGCAAATGAACAGTCTGAGAGTCGAGGACACGGCTGTGTATTACTGTGCAAGAG 
               
               
                   
                 GACGGACTCACTGGGGCCCCCAGGACTTTGACTACTGGGGCCAGGGAACCCTGGTCACC 
               
               
                   
                 GTCTCCTCA 
               
               
                   
               
               
                 SEQ ID 
                 CAGGTGCAGCTGCAGGAGTCGGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGAGACT 
               
               
                 183 
                 CTCCTGTGCAGCCTCTGGATTCACCTTTAGCAGCTATGCCATGAGCTGGGTCCGCCAGGC 
               
               
                   
                 TCCAGGGAAGGGGCTGGAGTGGGTCTCAGCTATTAGTGGTAGTGGTGGTAGCACATACT 
               
               
                   
                 ACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCAGAGACAATTCCAAGAACACGCTG 
               
               
                   
                 TATCTGCAAATGAACAGCCTGAGAGCCGAGGACACGGCCGTATATTACTGTGCGAAAGG 
               
               
                   
                 AGGAATGTATTACTATGGTTCGGGGAGCTCGTACTTTGACTACTGGGGCCAGGGAACCC 
               
               
                   
                 TGGTGACCGTCTCCTCA 
               
               
                   
               
               
                 SEQ ID 
                 CAGGTGCAGCTGGTGCAATCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGAGACT 
               
               
                 184 
                 CTCCTGTGCAGCCTCTGGATTCACCTTTAGCAGCTATGCCATGAGCTGGGTCCGCCAGGC 
               
               
                   
                 TCCAGGGAAGGGGCTGGAATGGGTCTCAGGTATTAGTGGTAGTGGTGGTAGCACATACT 
               
               
                   
                 ACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCAGAGACAATTCCAAGAACATGCTG 
               
               
                   
                 TTTCTGCAAATGAACAGCCCGAGAGCCGAGGACACGGCCGTATATTACTGTGCGAAGAA 
               
               
                   
                 AATAGCAGCAGCTGGTAAGCAACCTGTTGACTACTGGGGCCAGGGAACCCTGGTCACCG 
               
               
                   
                 TCTCCTCA 
               
               
                   
               
               
                 SEQ ID 
                 CAGGTGCAGCTACAGCAGTGGGGCGCAGGACTGTTGAAGCCTTCGGAGACCCTGTCCCT 
               
               
                 185 
                 CACCTGCGCTGTCTATGGTGGGTCCTTCAGTGGTTACTACTGGAGCTGGATCCGCCAGCC 
               
               
                   
                 CCCAGGGAAGGGGCTGGAGTGGATTGGGGAAATCAATCATAGTGGAAGCACCAACTAC 
               
               
                   
                 AACCCGTCCCTCAAGAGTCGAGTCACCATATCAGTAGACACGTCCAAGAACCAGTTCTC 
               
               
                   
                 CCTGAAGCTGAGCTCTGTGACCGCCGCGGACACGGCTGTGTATTACTGTGCGAGAAGGA 
               
               
                   
                 AGGTGTATGATTACGTTTGGGGGAGTTATCGCCTCCCCGGGTCGGTATCGTACTACTTTG 
               
               
                   
                 ACTACTGGGGCCAGGGAACCCTGGTCACCGTCTCCTCA 
               
               
                   
               
               
                 SEQ ID 
                 CAGGTCCAGCTGGTACAGTCTGGAGCAGAGGTGAAAAAGCCCGGGGAGTCTCTGAAGA 
               
               
                 186 
                 TCTCCTGTAAGGGTTCTGGATACAGCTTTACCAGCTACTGGATCGGCTGGGTGCGCCAGA 
               
               
                   
                 TGCCCGGGAAAGGCCTGGAGTGGATGGGGATCATCTATCCTGGTGACTCTGATACCAGA 
               
               
                   
                 TACAGCCCGTCCTTCCAAGGCCAGGTCACCATCTCAGCCGACAAGTCCATCAGCACCGC 
               
               
                   
                 CTACCTGCAGTGGAGCAGCCTGAAGGCCTCGGACACCGCCATGTATTACTGTGCGAGAC 
               
               
                   
                 TCCCGGGGAGAGCAGCTCGTCCAGACTACTGGGGCCAGGGCACCCTGGTCACCGTCTCC 
               
               
                   
                 TCA 
               
               
                   
               
               
                 SEQ ID 
                 CAGGTCACCTTGAAGGAGTCTGGGGGAGGCGTGGTCCAGCCTGGGAGGTCCCTGAGACT 
               
               
                 187 
                 CTCCTGTGCAGCCTCTGGATTCACCTTCAGTAGCTATGCTATGCACTGGGTCCGCCAGGC 
               
               
                   
                 TCCAGGCAAGGGGCTGGAGTGGGTGGCAGTTATATCATATGATGGAAGTAATAAATACT 
               
               
                   
                 ACGCAGACTCCGTGAAGGGCCGATTCACCATCTCCAGAGACAATTCCAAGAACACGCTG 
               
               
                   
                 TATCTGCAAATGAACAGCCTGAGAGCTGAGGACACGGCTGTGTATTACTGTGCGAGAGG 
               
               
                   
                 CCCCGGGGCAGTGGCTGGTACTAAGCCAAAGTACTACTTTGACTACTGGGGCCAGGGAA 
               
               
                   
                 CCCTGGTCACCGTCTCCTCA 
               
               
                   
               
               
                 SEQ ID 
                 GAGGTCCAGCTGGTGCAGTCTGGGGGAGGCGTGGTCCAGCCTGGGAGGTCCCTGAGACT 
               
               
                 188 
                 CTCCTGTGCAGCCTCTGGATTCACCTTCAGTAGCTATGCTATGCACTGGGTCCGCCAGGC 
               
               
                   
                 TCCAGGCAAGGGGCTGGAGTGGGTGGCAGTTATATCATATGATGGAAGTAATAAATACT 
               
               
                   
                 ACGCAGACTCCGTGAAGGGCCGATTCACCATCTCCAGAGACAATTCCAAGAACACGCTG 
               
               
                   
                 TATCTGCAAATGAACAGCCTGAGAGCTGAGGACACGGCTGTGTATTACTGTGCGAGGGC 
               
               
                   
                 CACGTATTACTATGATAGTAGTGGTTATAGGTTTGACTACTGGGGCCAGGGAACCCTGGT 
               
               
                   
                 CACCGTCTCCTCA 
               
               
                   
               
               
                 SEQ ID 
                 GAGGTCCAGCTGGTACAGTCTGGGGGAGGCTTGGTAGAACCGGGGGGGTCCCTTAGACT 
               
               
                 189 
                 CTCCTGTGCAGCCTCTCGATTCACTTTCAGTGACGCCTGGATGAGCTGGGTCCGCCAGGC 
               
               
                   
                 TCCAGGTAAGGGGCTGGAGTGGGTTGGCCGTATTAAAAGCAAAATAAGTGGTGGGACA 
               
               
                   
                 ACAGACTACGCTGCACCCGTGCAAGGCAGATTCACCATCTCAAGAGATGATTCAAAAAA 
               
               
                   
                 CACGCTGTATCTGCAAATGGACAGCCTGAAAACCGAGGACACAGCCGTGTATTACTGTG 
               
               
                   
                 CGAACCGAAACTTAGGCTACTGGGGCCAGGGCACCCTGGTGACCGTCTCCTCA 
               
               
                   
               
               
                 SEQ ID 
                 GAGGTCCAGCTGGTGCAGTCTGGGGCTGAGGTGAAGAAGCCTGGGGCCTCAGTGAAGGT 
               
               
                 190 
                 TTCCTGCAAGGCTTCTGGATACACCTTCACTAGCTATGCTATGCATTGGGTGCGCCAGGC 
               
               
                   
                 CCCCGGACAAAGGCTTGAGTGGATGGGATGGATCAACGCTGGCAATGGTAACACAAAA 
               
               
                   
                 TATTCACAGAAGTTCCAGGGCAGAGTCACCATGACCACAGACACATCCACGAGCACAGC 
               
               
                   
                 CTACATGGAGCTGAGGAGCCTGAGATCTGACGACACGGCCGTGTATTACTGTGCGAGAG 
               
               
                   
                 CTCGTTACTATGATAGTAGTGGTTATATTGCCCCATCGGGTTACTTTGACTACTGGGGCC 
               
               
                   
                 AGGGAACCCTGGTCACCGTCTCCTCA 
               
               
                   
               
               
                 SEQ ID 
                 CAGGTGCAGCTGGTGCAGTCTGGGGCTGAGGTGAAGAAGCCTGGGGCCTCAGTGAAGGT 
               
               
                 191 
                 TTCCTGCAAGGCTTCTGGATACACCTTCACTAGCTATGCTATGCATTGGGTGCGCCAGGC 
               
               
                   
                 CCCCGGACAAAGGCTTGAGTGGATGGGATGGATCAACGCTGGCAATGGTAACACAAAA 
               
               
                   
                 TATTCACAGAAGTTCCAGGGCAGAGTCACCATTACCAGGGACACATCCGCGAGCACAGC 
               
               
                   
                 CTACATGGAGCTGAGCAGCCTGAGATCTGAAGACACGGCTGTGTATTACTGTGCGAGAG 
               
               
                   
                 ATGGCCCCGCCGTTGATGGTGCTGAATACTTCCAGCACTGGGGCCAGGGCACCCTGGTC 
               
               
                   
                 ACCGTCTCCTCA 
               
               
                   
               
               
                 SEQ ID 
                 CAGCTGCAGCTGCAGGAGTCGGGTCCAGGACTGGTGAAGCCCTCGCAGACCCTCTCACT 
               
               
                 192 
                 CACCTGTGCCATCTCCGGGGACAGTGTCTCTAGCAACAGTGCTGCTTGGAACTGGATCA 
               
               
                   
                 GGCAGTCCCCATCGCGAGGCCTTGAGTGGCTGGGAAGGACTTACTACAGGTCCAAGTGG 
               
               
                   
                 TATAATGATTATGCAGTATCTCTGAAAAGTCGAATAACCATCAACCCGGACACATCCAA 
               
               
                   
                 GAACCAGTTCTCCCTGCAGCTGAACTCTGTGACTCCCGAGGACACGGCTGTATATTACTG 
               
               
                   
                 TGCAAGTTTGGCGAGTGGTTCCCCCCCTCCGGGGGACTACTGGGGCCAGGGAACCCTGG 
               
               
                   
                 TGACCGTCTCCTCA 
               
               
                   
               
               
                 SEQ ID 
                 CAGGTCACCTTGAAGGAGTCTGGGGGAGGCGTGGTCCAGCCTGGGAGGTCCCTGAGACT 
               
               
                 193 
                 CTCCTGTGCAGCCTCTGGATTCACCTTCAGTACCTATGGCATGCACTGGGTCCGCCAGGC 
               
               
                   
                 TCCAGGCAAGGGGCTGGAGTGGGTGGCACTTATATCATATGATGGAAGTAAAAAATACT 
               
               
                   
                 ATGCAAACTCCGTGAAGGGCCGATTCACCATCTCCAGAGACAATTCCAAGAACACGTTG 
               
               
                   
                 TATCTGCAAATGAAAAGTCTGAGAGCTGAGGACACGGCTATGTATTACTGTGCGAAAGG 
               
               
                   
                 CCCTATAGTGGGAGCGACTATGGACTACTGGGGCCAGGGAGCCCTGGTCACCGTCTCCT 
               
               
                   
                 CA 
               
               
                   
               
               
                 SEQ ID 
                 GAGGTGCAGCTGGTGCAGTCTGGGGCTGAGGTGAAGAAGCCTGGGTCCTCGGTGAAGGT 
               
               
                 194 
                 CTCCTGCAAGGCTTCTGGAGGCACCTTCAGCAGCTATGCTATCAGCTGGGTGCGACAGG 
               
               
                   
                 CCCCTGGACAAGGGCTTGAGTGGATGGGATGGATCAGCGCTTACAATGGTAACACAAAC 
               
               
                   
                 TATGCACAGAAGCTCCAGGGCAGAGTCACCATGACCACAGACACATCCACGAGCACAG 
               
               
                   
                 CCTACATGGAGCTGAGGAGCCTGAGATCTGACGACACGGCCGTGTATTACTGTGCGAGA 
               
               
                   
                 TGGTACGGTGACTACGGCCTTGACTACTGGGGCCAGGGAACCCTGGTCACCGTCTCCTC 
               
               
                   
                 A 
               
               
                   
               
               
                 SEQ ID 
                 GAGGTCCAGCTGGTGCAGTCTGGGGCTGAGGTGAAGAAGCCTGGGGCCTCAGTGAAGGT 
               
               
                 195 
                 TTCCTGCAAGGCTTCTGGATACACCTTCACTAGCTATGCTATGCATTGGGTGCGCCAGGC 
               
               
                   
                 CCCCGGACAAAGGCTTGCGTGGATGGGATGGATCAACGCTGGCAATGGTAACACAAAAT 
               
               
                   
                 ATTCAGAGAAGTTCGAAGGCAGAGTCACCATCACCAGGGACACATCCGCGAGCACAGC 
               
               
                   
                 CTACATGGAGCTGAGCAGCCTGAGATCTGAAGACACGGCTGTGTATTACTGTGCGAGGG 
               
               
                   
                 TCGCCAAATATTATTACGAGAGTGGTGGTTATCGGGCCTCCAACTGGTTCGACCCCTGGG 
               
               
                   
                 GCCAGGGCACCCTGGTCACCGTCTCCTCA 
               
               
                   
               
               
                 SEQ ID 
                 CAGGTGCAGCTGCAGGAGTCAGGTCCAGGACTGGTGAAGCCCTCGCAGACCCTCTCACT 
               
               
                 196 
                 CACCTGTGCCATCTCCGGGGACAGTGTCTCTAGCAACAGTGCTGCTTGGAACTGGATCA 
               
               
                   
                 GGCAGTCCCCATCGAGAGGCCTTGAGTGGCTGGGAAGGACATACTACAGGTCCAAGTGG 
               
               
                   
                 TATAATGATTATGCAGTATCTGTGAAAAGTCGAATAACCATCAACCCAGACACATCCAA 
               
               
                   
                 GAACCAGTTCTCCCTGCAGCTGAACTCTGTGACTCCCGAGGACACGGCTGTGTATTACTG 
               
               
                   
                 TGCAAGAGCGCCCCCTCCGACTGTTGGCTGGTACGCCCCCGTCTTTGACTACTGGGGCCA 
               
               
                   
                 GGGAACCCTGGTCACCGTCTCCTCA 
               
               
                   
               
               
                 SEQ ID 
                 CAGCTGCAGCTGCAGGAGTCCGGGGGAGGCTTAGTTCAGCCGGGGGGGTCCCTGAGACT 
               
               
                 197 
                 CTCCTGCTCAGCCTCTGGAATCAGCTTCAGAGATTACTGGATGCACTGGATCCGCCAAAC 
               
               
                   
                 TCCAGGGAAGGGGCTGGTGTGGGTCTCACGTATTAATCCTGATGGGAGTAGCACAAGCT 
               
               
                   
                 ACGCGGACTCCGTGAAGGGCCGATTCACCATCTCCAGAGACAATTCCAAGAACACGCTG 
               
               
                   
                 TATCTGCAAATGAACAGCCTGAGAGCTGAGGACACGGCTGTGTATTACTGTGCGAAAGT 
               
               
                   
                 TACGGGACGGAGAGTGGGAGCCCATGACTACTGGGGCCAGGGAACCCTGGTCACCGTCT 
               
               
                   
                 CCTCA 
               
               
                   
               
               
                 SEQ ID 
                 CAGGTGCAGCTGGTGCAGTCTGGGGCTGAGGTGAAGAAGCCTGGGGCCTCAGTGAAGGT 
               
               
                 198 
                 CTCCTGCAAGGCTTCTGGATACACCTTCACCGGCTACTATATGCACTGGGTGCGACAGGC 
               
               
                   
                 CCCTGGACAAGGGCTTGAGTGGATGGGATGGATCAACCCTAACAGTGGTGGCACAAACT 
               
               
                   
                 ATGCACAGAAGTTTCAGGGCAGGGTCACCATGACCAGGGACACGTCCATCAGCACAGCC 
               
               
                   
                 TACATGGAGCTGAGCAGGCTGAGATCTGACGACACGGCCGTGTATTACTGTGCCTTTGC 
               
               
                   
                 CCAGCCGGGCGCTGAGACGTTGAACTTCGATCTCTGGGGCCGTGGCACCCTGGTCACCG 
               
               
                   
                 TCTCCTCA 
               
               
                   
               
               
                 SEQ ID 
                 CAGGTACAGCTGCAGCAGTCAGGTCCAGGACTGGTGAAGCCCTCGCAGACCCTCTCACT 
               
               
                 199 
                 CACCTGTGCCATCTCCGGGGACAGTGTCTCTAGCAAAAGTGCTGCTTGGAACTGGATCA 
               
               
                   
                 GGCAGTCCCCATCGAGAGGCCTTGAGTGGCTGGGAAGGACATACTACAGGTCCAAATGG 
               
               
                   
                 AATAATGATTATGCATTATCTGTGAAAAGTCGAATAACCATCAACCCAGACACATCCAA 
               
               
                   
                 GAACCAGTTCTCCCTGCAGCTGAAGTCTGTGACTCCCGAGGACACGGCTCTGTATTACTG 
               
               
                   
                 TGTAAGACAAGTCGCGGGCGGTATGGACGTCTGGGGCCAAGGGACCACGGTCACCGTCT 
               
               
                   
                 CCTCA 
               
               
                   
               
               
                 SEQ ID 
                 CAGGTGCAGCTGGTGCAATCTGGGGGAGGCTTGGTACAGCCAGGGCGGTCCCTGAGACT 
               
               
                 200 
                 CTCCTGTACAGCTTCTGGATTCACCTTTGGTGATTATGCTATGAGCTGGTTCCGCCAGGC 
               
               
                   
                 TCCAGGGAAGGGGCTGGAGTGGGTCTCAGCTATTAGTGGTAGTGGTGGTAGCACATACT 
               
               
                   
                 ATGCAGACTCCGTGAAGGGCCGATTCACCATCTCCAGAGACAATTCCAAGAACACGCTG 
               
               
                   
                 TATCTGCAAATGAACAGCCTGAGAGCTGAGGACACGGCTGTGTATTACTGTGCGAAAGG 
               
               
                   
                 ATCGGTATATAGTGGGAGCTACTATATGCTCATTGACTACTGGGGCCAGGGCACCCTGG 
               
               
                   
                 TCACCGTCTCCTCA 
               
               
                   
               
               
                 SEQ ID 
                 CAGGTACAGCTGCAGCAGTCAGGTCCAGGACTGGTGAGGCCCTCGCAGACCCTCTCACT 
               
               
                 201 
                 CACCTGTGTCATCTCCGGGGACAGTGTCTCTAGCGGCAGTGCTGCTTGGAACTGGATCAG 
               
               
                   
                 GCAGTCCCCATCGAGAGGCCTTGAGTGGCTGGGAAGGACATATTATAGGGCCAAGTGGT 
               
               
                   
                 ATAATGAATATGCAGGGTCTGTGAAAAGCCGAATAACCATCAGTCCGGACACATCCAAG 
               
               
                   
                 AACCAGTTCTCCCTGCAACTGAACTCTGTGACTCCCGAGGACACGGCTGTGTATTTCTGT 
               
               
                   
                 ACAAGACAAGACAAAGACAACACGAGATATTCCGGTTTGGGCGTCTGGGGCCAAGGGA 
               
               
                   
                 CCACGGTGACCGTCTCCTCA 
               
               
                   
               
               
                 SEQ ID 
                 GAGGTGCAGCTGGTGGAGACCGGGGGAGGCTTAGTTCAGCCTGGGGGGTCCCTGAGACT 
               
               
                 202 
                 CTCCTGTGCAGCCTCTGAATTCACCCTTAGGAACTATGGCGTGAGCTGGGTCCGCCAGGC 
               
               
                   
                 TCCAGGGAAGGGGCTGGAGTGGGTCTCAGGTATGAGTGGTAGTGGTTATAGTACATACT 
               
               
                   
                 ACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCAGAGACAGTTCCAAGAACACGCTG 
               
               
                   
                 TTTCTGCAAATGGACAGCCTGAGAGCCGAGGACACGGCCATATATTACTGTGCGAGAGG 
               
               
                   
                 GCCCCGAATGTGGAGCAGTGGCATTGATGCTTTTGATATCTGGGGCCACGGGACAATGG 
               
               
                   
                 TGACCGTCTCTTCA 
               
               
                   
               
               
                 SEQ ID 
                 CAGGTGCAGCTACAGCAGTGGGGCGCAGGACTGTTGAAGCCTTCGGAGACCCTGTCCCT 
               
               
                 203 
                 CACCTGCGCTGTCTATGGTGGGTCCGTCAGTGGTTACTACTGGAGCTGGATCCGCCAGCC 
               
               
                   
                 CCCAGGGAAGGGGCTGGAGTGGATGGGGGAAATCCATCATAGTGGAAGCACCAACTAC 
               
               
                   
                 AACCCGTCCCTCAAGAGTCGAGTCACCATATCACTAGACACGCCCAAGAACCAGTTCTC 
               
               
                   
                 CCTGAAGCTAAGCTCTGTGACCGCCGCGGACACGGCTGTATATTACTGTGCGAGACGGG 
               
               
                   
                 ATTGGGCAGGAAAAAGGGTCTGGGGCCAGGGAACCCTGGTCACCGTCTCCTCA 
               
               
                   
               
               
                 SEQ ID 
                 CAGGTACAGCTGCAGCAGTCAGGTCCAGGACTATTAAAGCCCTCGCAGACCCTCTCACT 
               
               
                 204 
                 CACCTGTGCCATCTCCGGGGACAGTGTCTCTAGCAACACTGCTACTTGGAACTGGATCAG 
               
               
                   
                 GCAGTCCCCATCGAGAGGCCTTGAGTGGCTGGGAAGGACATACTACAGGTCCAAGTGGT 
               
               
                   
                 ATAAGGATAATGCACTGTCTGTGAAAAGTCGAATAACCATCAACCCAGACACATCCAAG 
               
               
                   
                 AACCAGTTCTCCCTGCAGCTGAACTCTGTGACTCCCGAGGACACGGCTGTGTATTACTGT 
               
               
                   
                 GCAGGAGGTCGGGCTGGTATTGCCGCTTTTGATATCTGGGGCCAAGGGACCACGGTCAC 
               
               
                   
                 CGTCTCCTCA 
               
               
                   
               
               
                 SEQ ID 
                 CAGGTGCAGCTGGTGCAATCTGGAGGAGGCTTGATCCAGCCTGGGGGGTCCCTGAGACT 
               
               
                 205 
                 CTCCTGTGCAGCCTCTGGGTTCACCGTCAGTAGCAACTACATGAGCTGGGTCCGCCAGGC 
               
               
                   
                 TCCAGGGAAGGGGCTGGAATGGGTCTCACTTATTTATAGTGATGGTCGCACAAACTATG 
               
               
                   
                 CAGACTCCGTGAAGGGCCGATTCACCATCTCCAGAGACAATTCCAAGAACACGCTGTAT 
               
               
                   
                 CTGCAAATGAACAGCCTGAGAGCCGAGGACACGGCCGTATATTACTGTGCGAAGGGGG 
               
               
                   
                 CCCTACAGGGCGAATGGCGGAGATTTGACTACTGGGGCCAGGGCACCCTGGTCACCGTC 
               
               
                   
                 TCCTCA 
               
               
                   
               
               
                 SEQ ID 
                 CAGGTGCAGCTACAGCAGTCAGGTCCAGGACTGGTGAAGCCCTCGCAGACCCTCTCACT 
               
               
                 206 
                 CACCTGTGCCATCTCCGGGGACAGTGTCTCTAGCAACAGTGCTGCTTGGAACTGGATCA 
               
               
                   
                 GGCAGTCCCCATCGAGAGGCCTTGAGTGGCTGGGAAGGACATATTACAGGTCCAAGTGG 
               
               
                   
                 TATAATGATTATGCAGTATCTGTGAAAAGTCGAATAACCATCAACCCAGACACATCCAA 
               
               
                   
                 GAACCAGTTCTCCCTGCAGCTGAACTCTGTGACTCCCGAGGACACGGCTGTGTATTACTG 
               
               
                   
                 TACAAGAACCAACCAGGGATACGGTGGTAACTCCGGGGTATTTGACTACTGGGGCCAGG 
               
               
                   
                 GAACCCTGGTCACCGTCTCCTCA 
               
               
                   
               
               
                 SEQ ID 
                 CAGGTGCAGCTACAGCAGTCAGGTCCAGGACTGGTGAAGCCCTCGCAGACCCTCTCACT 
               
               
                 207 
                 CACCTGTGCCATCTCCGGGGACAGTGTCTCTGGCAACAGTGCTGCTTGGAACTGGATCA 
               
               
                   
                 GGCAGTCCCCATCGAGAGGCCTTGAGTGGCTGGGAAGGACATACTACAGGTCCAAGTGG 
               
               
                   
                 TATAATGATTATGCAGTATCTGTGAAAAGTCGAATAACCATCAACCCAGACACATCCAA 
               
               
                   
                 GAACCAGTTCTCCCTGCAGTTGAATTCTGTGACTCCCGAGGACACGGCTGTGTATTACTG 
               
               
                   
                 TGCGAGGATAGTGGGAGGTGCCGTTGACTGCTGGGGCCAGGGAACCCTGGTGACCGTCT 
               
               
                   
                 CCTCA 
               
               
                   
               
               
                 SEQ ID 
                 GAGGTGCAGCTGGTGCAGTCTGGGGCTGAGGTGAAGAAGCCTGGGGCCTCAGTGAAGG 
               
               
                 208 
                 TTTCCTGCAAGGCTTCTGGATACACCTTCACTAGCTATGCTATGCATTGGGTGCGCCAGG 
               
               
                   
                 CCCCCGGACAAAGGCTTGAGTGGATGGGATGGATCAACGCTGGCAATGGTAACACAAA 
               
               
                   
                 ATATTCACAGAAGTTCCAGGGCAGAGTCACCATTACCAGGGACACATCCGCGAGCACAG 
               
               
                   
                 CCTACATGGAGCTGAGCAGCCTGAGATCTGAAGACACGGCTGTGTATTACTGTGCGAGA 
               
               
                   
                 GTTAGAGTGGGAGCTACTACTGTTTACGACAGCTGGTTCGACCCCTGGGGCCAGGGAAC 
               
               
                   
                 CCTGGTGACCGTCTCCTCA 
               
               
                   
               
               
                 SEQ ID 
                 CAGGTGCAGCTGGTGCAGTCTGGGGGAGGCTTGGTACAGCCTGGGGGGTCCCTGAGACT 
               
               
                 209 
                 CTCCTGTGCAGCCTCTGGATTCACCTTTAGCAGCTATGCCATGAGCTGGGTCCGCCAGGC 
               
               
                   
                 TCCAGGGAAGGGGCTGGAGTGGGTCTCAGCTATTAGTGGTAGTGGTGGTAGCACATACT 
               
               
                   
                 ACGCAGACTCCGTGAAGGGCCGGTTCACCATCTCCAGAGACAATTCCAAGAACACGCTG 
               
               
                   
                 TATCTGCAAATGAACAGCCTGAGAGCCGAGGACACGGCCGTATATTACTGTGCGAAAGA 
               
               
                   
                 TGGGGGGTCCAGCCCATACTATGATAGTAGTGGTTTACTACCCTGGTACTTCGATCTCTG 
               
               
                   
                 GGGCCGTGGCACCCTGGTCACCGTCTCCTCA 
               
               
                   
               
               
                 SEQ ID 
                 CAGGTGCAGCTGCAGGAGTCGGGGGGAGGCTTGGTCCAGCCTGGGGGGTCCCTGAGACT 
               
               
                 210 
                 CTCCTGTGCAGCCTCTGGATTCACCTTCAGTAGCTATGCTATGCACTGGGTCCGCCAGGC 
               
               
                   
                 TCCAGGGAAGGGACTGGAATATGTTTCAGCTATTAGTAGTAATGGGGGTAGCACATATT 
               
               
                   
                 ATGCAAACTCTGTGAAGGGCAGATTCACCATCTCCAGAGACAATTCCAAGAACACGCTG 
               
               
                   
                 TATCTTCAAATGGGCAGCCTGAGAGCTGAGGACATGGCTGTGTATTACTGTGCGAGAGC 
               
               
                   
                 TAAGTTTTGGACATACTACTTTGACTACTGGGGCCAGGGAACCCTGGTGACCGTCTCCTC 
               
               
                   
                 A 
               
               
                   
               
               
                 SEQ ID 
                 CAGGTGCAGCTACAGCAGTGGGGCGCAGGACTGTTGAAGCCTTCGGAGACCCTGTCCCT 
               
               
                 211 
                 CACCTGCGCTGTCTATGGTGGGTCCTTCAGTGGTTACTACTGGAGCTGGATCCGCCAGCC 
               
               
                   
                 CCCAGGGAAGGGGCTGGAGTGGATTGGGGAAATCAATCATAGTGGAAGCACCAACTAC 
               
               
                   
                 AACCCGTCCCTCAAGAGTCGAGTCACCATATCAGTAGACACGTCCAAGAACCAGTTCTC 
               
               
                   
                 CCTGAAGCTGAGCTCTGTGACCGCCGCGGACACGGCTGTGTATTACTGTGCGAGAGGCG 
               
               
                   
                 GTGGTTCGGGGAGTTATTATAAGAGGTTCTTTGACTACTGGGGCCAGGGAACCCTGGTC 
               
               
                   
                 ACCGTCTCCTCA 
               
               
                   
               
               
                 SEQ ID 
                 GAGGTGCAGCTGGTGCAGTCTGGAGCTGAGGTGAGGAAGCCTGGGGCCTCAGTGAAGG 
               
               
                 212 
                 TCTCCTGCAAGGCTTCTGGTTACACATTTACCAGTTATGCCATCAGCTGGGTGCGACAGG 
               
               
                   
                 CCCCTGGACAAGGGCTTGAGTGGATGGGGTGGATCAGCGCTTACGACGGTAACACAAAC 
               
               
                   
                 TATGCACAGAAGCTCCAGGGCAGAGTCACCATGACCACAGACACATCCACGAGCACAG 
               
               
                   
                 CCTACATGGAGGTGAGGAGCCTGAGATCTGACGACACGGCCGTGTATTACTGTGCGAGA 
               
               
                   
                 GATGGTACGGTCCGAAGGGTAGTGGGAGCTACTACCCCTGGAAACTTTGACTACAGGGG 
               
               
                   
                 CCAGGGAACCCTGGTCACCGTCTCCTCA 
               
               
                   
               
               
                 SEQ ID 
                 GAGGTGCAGCTGGTGCAGTCTGGGGGAGGCGTGGTCCAGCCTGGGAGGTCCCTGAGACT 
               
               
                 213 
                 CTCCTGTGCAGCGTCTGGATTCACCTTCAGTAGCTATGGCATGCACTGGGTCCGCCAGGC 
               
               
                   
                 TCCAGGCAAGGGGCTGGAGTGGGTGGCAGTTATATGGTATGATGGAAGTAATAAATACT 
               
               
                   
                 ATGCAGACTCCGTGAAGGGCCGATTCACCATCTCCAGAGACAATTCCAAGAACACGCTG 
               
               
                   
                 TATCTGCAAATGAACAGCCTGAGAGCCGAGGACACGGCTGTGTATTACTGTGCGAGAGA 
               
               
                   
                 TCTGAATCGAGGATATTGTAGTGGTGGTAGCTGCTTTGGCTACTGGGGCCAGGGAACCC 
               
               
                   
                 TGGTCACCGTCTCCTCA 
               
               
                   
               
               
                 SEQ ID 
                 CAGGTGCAGCTGCAGGAGTCTGGGGGAGGCTTGGTACAGCCGGGGGGGTCCCTGAGACT 
               
               
                 214 
                 CTCCTGTGCAGCCTCTGGATTCACCTTTAGCAGCTATGCCATGAGCTGGGTCCGCCAGGC 
               
               
                   
                 TCCAGGGAAGGGGCTGGAGTGGGTTTCATACATTAGTAGTAGTGGTACTACCATATACT 
               
               
                   
                 ACGCAGACTCTGTGAAGGGCCGATTCACCGTCTCCAGAGACAATGCCAAGAACTCACTG 
               
               
                   
                 TATCTGCAAATGAACAGCCTGAGAGCCGAGGACACGGCCGTGTATTACTGTGCGAGGGA 
               
               
                   
                 TTATAGCAGCTCGGGGGAGTGCTTTGACTACTGGGGCCAGGGAACCCTGGTCACCGTCT 
               
               
                   
                 CCTCA 
               
               
                   
               
               
                 SEQ ID 
                 GAGGTGCAGCTGGTGCAGTCTGGGGGAGGCGTGGTCCAGCCTGGGAGGTCCCTGAGACT 
               
               
                 215 
                 CTCCTGTGCAGCGTCTGGATTCACCTTCAGTAGCTATGGCATGCACTGGGTCCGCCAGGC 
               
               
                   
                 TCCAGGCAAGGGGCTGGAGTGGGTGGCAGTTATATGGTATGATGGAAGTAATAAATACT 
               
               
                   
                 ATGCAGACTCCGTGAAGGGCCGATTCACCATCTCCAGAGACAATTCCAAGAACACGCTG 
               
               
                   
                 TATCTGCAAATGAACAGCCTGAGAGCCGAGGACACGGCTGTGTATTACTGTGCGAGAGA 
               
               
                   
                 TCAGGCAGCTATGGTAGGCTACTTTGACTACTGGGGCCAGGGAACCCTGGTCACCGTCT 
               
               
                   
                 CCTCA 
               
               
                   
               
               
                 SEQ ID 
                 CAGGTCACCTTGAAGGAGTCTGGGGGAGGCGTGGTCCAGCCTGGGAGGTCCCTGAGACT 
               
               
                 216 
                 CTCCTGTGCAGCCTCTGGATTCATCTTCAGTAACTATGCTATACACTGGGTCCGCCAGGC 
               
               
                   
                 TCCAGGCAAGGGGCTGGAGTGGGTGGCAGTTATATCATATGATGGAAGTAATAAATACT 
               
               
                   
                 ACGCAGACTCCGTGAAGGGCCGATTCACCATCTCCAGAGACAATTCCAAGAACACGCTG 
               
               
                   
                 TATCTGCAAATGAACAGCCTGAGAGCTGAGGACACGGCTGTGTATTACTGTGCGAGGAC 
               
               
                   
                 TTTTGCGGGGTATAGCAGCAAACTGGGGTACTTCGATCTCTGGGGCCGTGGCACCCTGGT 
               
               
                   
                 CACCGTCTCCTCA 
               
               
                   
               
            
           
         
       
     
     Exemplary VL amino acid sequences of CLEC2D antibodies of the disclosure are shown in Table 4 below. VL amino acid sequences having at least 50% identity, at least 55% identity, at least 60% identity, at least 65% identity, at least 70% identity, at least 75% identity, at least 80% identity, at least 85% identity, at least 90% identity, at least 91% identity, at least 92% identity, at least 93% identity, at least 94% identity, at least 95% identity, at least 96% identity, at least 97% identity, at least 98% identity, at least 99% identity, at least 99.5% identity, at least 99.8% identity, at least 99.9% identity or 100% identity to the sequences listed in Table 4 are considered within the scope of the disclosure. 
     
       
         
           
               
             
               
                 TABLE 4 
               
             
            
               
                   
               
               
                 VL Amino Acid Sequences 
               
            
           
           
               
               
            
               
                 SEQ 
                   
               
               
                 ID 
                 VL Amino Acid Sequence 
               
               
                   
               
               
                 SEQ 
                 ETTLTQSPATLSVSLGERATLSCRASQSIGSNLVWYQL 
               
               
                 ID 
                 KPGQGPRLVIYSATSRATGIPARFSGSGSGTEFILSIS 
               
               
                 217 
                 NLQSEDLAVYYCQQYGSSPPTTFGQGTRLEIKR 
               
               
                   
               
               
                 SEQ 
                 EIVMTQSPATLSLSPGERATLSCRASQSVSSSYLAWYQ 
               
               
                 ID 
                 QKPGRAPRLLIYGASNRATGIPDRFSGSGSGTDFTLII 
               
               
                 218 
                 SRLEPEDFALYYCQQYGSSPGTFGQGTKVDIKR 
               
               
                   
               
               
                 SEQ 
                 DVVMTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQ 
               
               
                 ID 
                 KPGQAPRLLIYDASNRATGIPARFSGSGSGTDFTLTIS 
               
               
                 219 
                 SLEPEDFAVYYCQQRSNWPRTFGQGTKLEIKR 
               
               
                   
               
               
                 SEQ 
                 EIVLTQSPDSLAVSLGERATITCKSSRNILYSGNNKNF 
               
               
                 ID 
                 LAWYQHKPGQPPKLLIYWASTRESGVPDRFSGSGSGTD 
               
               
                 220 
                 FTLTINSLEAEDAATYYCHQSSSLPHTFGPGTKVDIKR 
               
               
                   
               
               
                 SEQ 
                 ETTLTQSPGTLSLSPGQRATLSCRASESVSKSYLLWYQ 
               
               
                 ID 
                 QKPGQAPRLLIYGASTRASGIPNRFSGSGSGTDFTLTI 
               
               
                 221 
                 SRLEPEDSAVYYCQHYGSSRTFGQGTRLEIKR 
               
               
                   
               
               
                 SEQ 
                 ETTLTQSPGTLSLSPGERATLSCRASQSISSTYLAWYQ 
               
               
                 ID 
                 QKPGQAPRLLIYGASTRATGIPDRFSGSGSGTDFTLSI 
               
               
                 222 
                 SRLEPEDFAVYYCQQYGNSPPGATFGQGTRLEIKR 
               
               
                   
               
               
                 SEQ 
                 DIQLTQSPSSLSASVGERVTITCRSSQALRNVVGLGDD 
               
               
                 ID 
                 LAWYQHTPGSAPKILIYSTSTLQSGVSSRFSGGKSGRD 
               
               
                 223 
                 FTLTIDRLQPGDSATYYCLQHHDFPFTFGPGTKVEIKR 
               
               
                   
               
               
                 SEQ 
                 DVVMTQSPLSLPVTPGEPASISCRSSQSLLNSNGYNYL 
               
               
                 ID 
                 EWYLQKPGQSPQLLIYLGSNRASGVPDRFSGSGSGTDF 
               
               
                 224 
                 TLKISRVEADDAGVYYCMQSLQTPLTFGGGTKLEIKR 
               
               
                   
               
               
                 SEQ 
                 ETTLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQ 
               
               
                 ID 
                 QKPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTI 
               
               
                 225 
                 SRLEPEDFAVYYCQQYGSSPRITFGQGTRLEIKR 
               
               
                   
               
               
                 SEQ 
                 DVVMTQSPATLSVSPGERATLSCRASQSVSSNLAWYQQ 
               
               
                 ID 
                 KPGQAPRLLIYGASTRATGIPARFSGSGSGTEFTLTIS 
               
               
                 226 
                 SLQSEDFAVYYCQQYNNWPPMYTFGQGTKLEIKR 
               
               
                   
               
               
                 SEQ 
                 DVVMTQSPATLSVSPGERVTLSCRASQSVRDNVGWYKQ 
               
               
                 ID 
                 KPGQPPRLVIYGASTRATGIPARISGSGSGTEFTLTIS 
               
               
                 227 
                 SLQSEDFAVYYCQQFNNWPYTFGQGTKLEIKR 
               
               
                   
               
               
                 SEQ 
                 DIQMTQSPSSLSASVGDRVTITCRASQSISSYLNWYQQ 
               
               
                 ID 
                 KPGKAPNLLIYAASSLHTGVPSRFSGSGSGTDFTLTIS 
               
               
                 228 
                 SLQPEDFATYYCQQSYSIPRTFGQGTKVEIKR 
               
               
                   
               
               
                 SEQ 
                 DVVMTQSPATLSVTPGERATLSCRASQSVNSNVAWYQQ 
               
               
                 ID 
                 KPGQAPRLLIYDVSTRATDIPARFSGSGSGTDFTLTIS 
               
               
                 229 
                 RLDPEDFAVYYCQQCASSPPVTFGGGTKLEIKR 
               
               
                   
               
               
                 SEQ 
                 EIVMTQSPATLSLSPGERATLSCGASQSVSSSYLAWYQ 
               
               
                 ID 
                 QKPGLAPRLLIYDASSRATGIPDRFSGSGSGTDFTLTI 
               
               
                 230 
                 SRLEPEDFAVYYCQQYGSSPRVTFGGGTKVDIKR 
               
               
                   
               
               
                 SEQ 
                 DVVMTQSPGTLSLSPGERATLSCRASQSVSSSALAWFQ 
               
               
                 ID 
                 QKPGQAPRLLIYDSSSRATGIPDSFSGSGSGTEFTLTI 
               
               
                 231 
                 SSLQPEDFATYYCQQFNTYPNTFGQGTKLEIKR 
               
               
                   
               
               
                 SEQ 
                 DIQMTQSPLSLPVTPGEPASISCRSSQSLLHSNGYNYL 
               
               
                 ID 
                 DWFLQKPGQSPRLLIYMGSSRASGVPERFSGSGSGTDF 
               
               
                 232 
                 TLKISRVEAEDVGVYYCMQTLHTVTFGGGTKVEIKR 
               
               
                   
               
               
                 SEQ 
                 ETTLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQ 
               
               
                 ID 
                 QKPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTI 
               
               
                 233 
                 SRLEPEDFAVYYCQQYGSSLLFGQGTRLEIKR 
               
               
                   
               
               
                 SEQ 
                 DIQLTQSPSFLSASVGDRVTITCRASQGISSSLAWYQQ 
               
               
                 ID 
                 KPGKAPKLLIYAASTLQSGVPSRFSGSGSGTDFTFTIS 
               
               
                 234 
                 SLQPEDIATYYCQQYDNLPPLTFGGGTKVEIKR 
               
               
                   
               
               
                 SEQ 
                 DVVMTQSPLSLPVTPGEPASISCRSSQSLLHSNGYNYL 
               
               
                 ID 
                 DWYLQKPGQSPQLLIYLGSNRASGVPDRFSGSGSGTDF 
               
               
                 235 
                 TVKISRVEAEDVGVYYCMQALQTPYTFGQGTKLEIKR 
               
               
                   
               
               
                 SEQ 
                 EIVLTQSPLSLPVTLGQPASISCRSCQSLVYSDGNTYL 
               
               
                 ID 
                 NCFQQRPGQSPRRLIYKVSNRDSGVPDRFSGSGSGTDF 
               
               
                 236 
                 TLEISRVEAEDVGIYFCMQGLQTPFTFGPGTKVDIKR 
               
               
                   
               
               
                 SEQ 
                 DVVMTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQ 
               
               
                 ID 
                 QKPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTI 
               
               
                 237 
                 SRLEPEDFAVYYCQQYGSSPALTFGGGTKLEIKR 
               
               
                   
               
               
                 SEQ 
                 EIVMTQSPLSLPVTPGEPASISCRSSQSLLHSNGYNYL 
               
               
                 ID 
                 DWYLQKPGQSPQLLIYLGSTRASGVPDRFSGSGSGTDF 
               
               
                 238 
                 TLKISRAEAEDVGVYYCMQALHTPWTFGLGTKVDIKR 
               
               
                   
               
               
                 SEQ 
                 DIQMTQSPATLSVSPGERATLFCRASEGLTTNLAWYQH 
               
               
                 ID 
                 KPGQAPRLLIYAASTRATGVPARFSGSGSGTDFTLTIS 
               
               
                 239 
                 SLQSEDSAVYYCQQYNHWPLYTFGQGTKVEIKR 
               
               
                   
               
               
                 SEQ 
                 DIQLTQSPSTLSLSPGERATLSCRASQSVSSYLAWYQQ 
               
               
                 ID 
                 KSGQAPRLLIYDASNRATGIPARFSGSGSGTDFTLTIS 
               
               
                 240 
                 SLEPEDFAVYYCQQGSNWPLTFGGGTKVEIKR 
               
               
                   
               
               
                 SEQ 
                 DIVMTHTPLSSPVTLGQPASISCRSSQSLEHTDGNTYL 
               
               
                 ID 
                 SWLHQRPGQPPRLLIYKVSTRFSGVPDRFSGSGAGTDF 
               
               
                 241 
                 TLKISRVEAEDVGVYYCVQATHYPRTFGHGTKVEIKR 
               
               
                   
               
               
                 SEQ 
                 EIVLTQSPGTLSLSPGERATLSCRASQSISGSYLAWYQ 
               
               
                 ID 
                 QKRGQAPRLLIYDASSRAEGIPDRFIGSGSGTDFTLTI 
               
               
                 242 
                 SRLEPEDFAMYYCQQYGSSPIFTFGPGTKVDIKR 
               
               
                   
               
               
                 SEQ 
                 EIVLTQSPDSLPVTPGEPASISCRSSQSLLHSNGNNYL 
               
               
                 ID 
                 DWYLQKPGQSPQLLIYLGSNRASGVPDRFSGSGSGTDF 
               
               
                 243 
                 TLKLSRVEAEDVGVYYCMQGLQIPITFGPGTKVDIKR 
               
               
                   
               
               
                 SEQ 
                 DIQMTQSPSSVSASVGDRVTITCRASQNIRHWLVWYQQ 
               
               
                 ID 
                 KLGQAPKLLIYAASNLQSGVPSRFSGSGSGTEFTLTIN 
               
               
                 244 
                 SLQAEDFATYYCLQHNSYPWTFGQGTKVEIKR 
               
               
                   
               
               
                 SEQ 
                 EIVLTQSPDFQSVTPKQKVTITCRASQSIGGSLHWYQQ 
               
               
                 ID 
                 KPGQSPKLIIKYASQSFSGVPSRFSGSGSGTDFTLTID 
               
               
                 245 
                 SLEAEDAATYYCHQSISLPLTFGGGTKVDIKR 
               
               
                   
               
               
                 SEQ 
                 ETTLTQSPGTLSLSPGEGATLSCRASQSVTSNYLAWYQ 
               
               
                 ID 
                 QKPGQAPRLLIYGASYRATGIPDRFSGSGSGTDFTLTI 
               
               
                 246 
                 SRLEPEDFAVYYCQQYASSVTFGQGTRLEIKR 
               
               
                   
               
               
                 SEQ 
                 DVVMTQSPATLSVSPGERATLSCRASQSISSNLAWYQQ 
               
               
                 ID 
                 KPGQAPRLLIYGASTRATGIPARFSGSGSGTEFTLTIS 
               
               
                 247 
                 SLQSEDFAVYYCQQYNNWPRTFGQGTKLEIKR 
               
               
                   
               
               
                 SEQ 
                 DIQLTQSPDSLAVSLGERATINCKSSQSVLYSSNNKNY 
               
               
                 ID 
                 LAWYQQKPGQPPKLLIYWASARESGVPDRFSGSGSGTD 
               
               
                 248 
                 FTLTINSLQAEDVAVYYCQQFYSPPRTFGQGTKVEIKR 
               
               
                   
               
               
                 SEQ 
                 EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQ 
               
               
                 ID 
                 QKPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTI 
               
               
                 249 
                 SRLEPEDFAVYYCQQYGSSPPGTFGGGTKVDIKR 
               
               
                   
               
               
                 SEQ 
                 EIVLTQSPGTLSLSPGERATLSCRASQSLSTNLAWYQQ 
               
               
                 ID 
                 KPGQAPRLLIYGASTRATGIPARFSGSGSGTEFTLTIT 
               
               
                 250 
                 SLQSEDFAVYYCQQYHNWPPYTFGQGTKVEIKR 
               
               
                   
               
               
                 SEQ 
                 DIQMTQSPSTLSASVGDRVTITCRASQSISSWLAWYQQ 
               
               
                 ID 
                 KPGKAPKLLIYKASSLESGVPSRFSGSGSGTEFTLTIS 
               
               
                 251 
                 SLQPDDFATYYCQQYNSYWTFGQGTKVEIKR 
               
               
                   
               
               
                 SEQ 
                 ETTLTQSPGTLSLSPGEGATLSCRASHSVGANYIAWYQ 
               
               
                 ID 
                 QKPGQAPRLLIHTASKRATGVPERFSGSGSGTDFTLSI 
               
               
                 252 
                 SRLEPEDFAVYHCQQYAAAPITFGQGTRLEIKR 
               
               
                   
               
               
                 SEQ 
                 EIVMTQSPSSLSASVGDRVIITCRASQGIANYLAWYQQ 
               
               
                 ID 
                 KPGKGPKLLIYASSTLQSGVPSRFSGSGSGTDFTLTIS 
               
               
                 253 
                 GLQPEDVATYYCQKYNSVPLTFGGGTKVDIKR 
               
               
                   
               
               
                 SEQ 
                 DVVMTQSPVSLAVSLGERATINCKSSQSVLYRTNNKNY 
               
               
                 ID 
                 LAWYQQKPGQPPKLLIYWASTRESGVPDRFSGSGSGTD 
               
               
                 254 
                 FTLTISSLQPEDVAVYYCQQYYNLPRSFGQGTKLEIKR 
               
               
                   
               
               
                 SEQ 
                 DIVMTHTPDSLAVSLGERATINCKSNRSVLYSPNNQNY 
               
               
                 ID 
                 LGWYQQKPGQPPKLLIYWASTRDSGAPDRFSGSGSGTD 
               
               
                 255 
                 FTLTINSLQAEDVAVYYCQQYASTPYTFGQGTKVEIKR 
               
               
                   
               
               
                 SEQ 
                 DVVMTQSPATLSLSPGERATLSCRASESVNSNFLAWYQ 
               
               
                 ID 
                 QKPGQAPRLLIYAASTRATGIPARFSGSGSGTEFTLII 
               
               
                 256 
                 TSLQSEDFAVYYCQQYNNWPLTFGGGTKLEIKR 
               
               
                   
               
               
                 SEQ 
                 DVVMTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQ 
               
               
                 ID 
                 KPGQAPRLLIYDASNRATGIPARFSGSGSGTDFTLTIS 
               
               
                 257 
                 SLEPEDFAVYYCQQRSNWSLTFGGGTKLEIKR 
               
               
                   
               
               
                 SEQ 
                 ETTLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQ 
               
               
                 ID 
                 QKPGQAPRLLIYGASTRATGIPDRFSGSGSGTDFTLTI 
               
               
                 258 
                 GRLEPEDFAVYYCQHYGPSRRITFGQGTRLEIKR 
               
               
                   
               
               
                 SEQ 
                 ETTLTQSPDTLSVSPGGRATLSCRASQSIGSNLAWYQQ 
               
               
                 ID 
                 KPGQSPRLLIYDASTRATGIPARFSGSGSGTEFTLTIS 
               
               
                 259 
                 SLESEDFVLYYCQQHGEWPTFGQGTRLEIKR 
               
               
                   
               
               
                 SEQ 
                 DVVMTQSPATLSLSPGERATLSCRASQSVGNSLAWYQQ 
               
               
                 ID 
                 KPGQAPRLLIYDASNRATGIPARFSGSGSGTDFTLTIT 
               
               
                 260 
                 SLEPEDFAIYYCQQRGTWPPLTFGGGTKLEIKR 
               
               
                   
               
               
                 SEQ 
                 DVVMTQSPSSLSASVGDTVTITCRASQSITNWLAWYQQ 
               
               
                 ID 
                 KPGKAPKRLIYGASSLQSGVPSRFSGSGSGTEFTLTIS 
               
               
                 261 
                 SLQPEDFATYYCQQYTNYPRTFGQGTKLEIKR 
               
               
                   
               
               
                 SEQ 
                 DIQMTQSPSTLSASVGDRVTITCRARQSISNRLAWYQQ 
               
               
                 ID 
                 KPGRAPNVLIYKASTLANGVPSRFSGSGSGTEFTLTIS 
               
               
                 262 
                 SLQPDDFATYYCQQYQSYWTFGPGTKVEIKR 
               
               
                   
               
               
                 SEQ 
                 DIQLTQSPATLSLSPGERATLSCKASQSVSSYLAWYQQ 
               
               
                 ID 
                 KLGQAPRLLIYDASNRATGIPARFSASGSGTDFTLTIS 
               
               
                 263 
                 SLQPEDVATYYCQKYNSPPRTFGQGTKVEIKR 
               
               
                   
               
               
                 SEQ 
                 ETTLTQSPGTLSLSPGERVSLSCRASQNVYSNFLAWYQ 
               
               
                 ID 
                 QRPGQAPSLLIYGASSRAAGVPDRFSGSGSGTDFALTI 
               
               
                 264 
                 SRVEPEDFAVYYCQQYGTSPITFGQGTRLEIKR 
               
               
                   
               
               
                 SEQ 
                 EIVLTQSPRSSPVTLGQPASISCRSSQSLEHGDGNTYL 
               
               
                 ID 
                 SWLQQRPGQPPRLLIYKVSNRLSGVPDRFSGSGAGTDF 
               
               
                 265 
                 TLKISRVEAEDVGVYYCMQGIYWPRTFGQGTRLEIKR 
               
               
                   
               
               
                 SEQ 
                 ETTLTQSPVTLSLSPGDRATLSCRASQSVSSTSLAWYQ 
               
               
                 ID 
                 HKPGQAPRLLIYGASRRATGIPDRFSGSGSGTDFTLTI 
               
               
                 266 
                 NRLEPEDFAVYYCQHYGSSPPITFGQGTRLEIKR 
               
               
                   
               
               
                 SEQ 
                 ETTLTQSPATLSVSPGERATLSCRASQSVGSKLAWYQQ 
               
               
                 ID 
                 KPGQAPRLLIYGASTRATGVPVRFSGSGSGTEFTLTIS 
               
               
                 267 
                 SLQSEDFAVYYCQQYNNWPPITFGQGTRLEIKR 
               
               
                   
               
               
                 SEQ 
                 EIVLTQSPLSLPVTPGEPASISCRSSQSLLHSNGYNYL 
               
               
                 ID 
                 DWYLQKPGQSPQLLIYLGSNRASGVPDRFSGSGSGTDF 
               
               
                 268 
                 TLKISRVEAEDVGVYYCMQTLQTPLTFGGGTKVDIKR 
               
               
                   
               
               
                 SEQ 
                 DVVMTQSPDSLAVSLGERATINCKSSQSVLYSSNNKNY 
               
               
                 ID 
                 LAWYQQKPGQPPKLLIYWASTRESGVPDRFSGSGSGTD 
               
               
                 269 
                 FTLTISSLQAEDVAVYYCQQYYSSTPYTFGQGTKLEIK 
               
               
                   
                 R 
               
               
                   
               
               
                 SEQ 
                 DIVMTHTPLSLSVTPGQPASISCKSSQSLLGGDGKTYL 
               
               
                 ID 
                 YWYLQKPGQPPQLLLYEVSNRFSGVPDRFSGSGAATDF 
               
               
                 270 
                 TLKISRVEAEDVGVYYCMQSTQFPWTFGQGTKVEIKR 
               
               
                   
               
               
                 SEQ 
                 ETTLTQSPGTLSLSAGERATLSCRASQSVSSSYLAWYQ 
               
               
                 ID 
                 QKPGQAPRLLIYAASYRATGIPDRFSGRGSGTEFTLTI 
               
               
                 271 
                 SSLQSEDFAVYYCQQYNNWPPITFGQGTRLEIKR 
               
               
                   
               
               
                 SEQ 
                 DVVMTQSPATLSVSPGERATLSCRASQSVSSNLAWYQQ 
               
               
                 ID 
                 KPGQAPRLLIYDASTRATGIPARFSGSGSGTEFTLTIS 
               
               
                 272 
                 SLQSEDFAVYYCQHYNNWPHTFGQGTKLEIKR 
               
               
                   
               
               
                 SEQ 
                 ETTLTQSPGTLSLSPGERATLSCRASQSVSSNSLAWYQ 
               
               
                 ID 
                 QKPGQAPRLLIYGASSRASGIPDRFNGSGSGTDFTLTI 
               
               
                 273 
                 NRLEPEDFAVYYCQQYGNSQTFGQGTRLEIKR 
               
               
                   
               
               
                 SEQ 
                 DVVMTQSPATLSVSPGERATLSCRASQSVSSNLAWYQQ 
               
               
                 ID 
                 KPGQAPRLLIYGASTRATGIPARFSGSGSGTEFTLTIS 
               
               
                 274 
                 SLQSEDFAVYYCQQYNNWPRTFGQGTKLEIKR 
               
               
                   
               
               
                 SEQ 
                 DVVMTQSPLSLPVTLGQPASISCRSSQSLVYSDGNTYL 
               
               
                 ID 
                 NWFQQRPGQSPRRLIYKVSNRDSGVPDRFSGSGSGTDF 
               
               
                 275 
                 TLKISRVEAEDVGVYYCMQGTHWPRTFGGGTKLEIKR 
               
               
                   
               
               
                 SEQ 
                 DIQMTQSPSTLSASVGDRVTITCRASQSISRWLAWYQQ 
               
               
                 ID 
                 KPGKAPKLLIYKASTIKSGVPSRFSASGSGTEFTLTIS 
               
               
                 276 
                 SLQPEDFATYYCQHYKSDSRTFGQGTKVEIKR 
               
               
                   
               
               
                 SEQ 
                 DVVMTQSPSSLAASVGDRITITCRPSQDIGTYLNWYQQ 
               
               
                 ID 
                 KAGEAPKLLIYAASNLHSGVSSRFRGVGSGTQFTLTIS 
               
               
                 277 
                 SLQPEDFATYYCHQSYGPRTFGQGTKLEIKR 
               
               
                   
               
               
                 SEQ 
                 ETTLTQSPATLSVSPGERATLSCRASQSVSSNLAWYQQ 
               
               
                 ID 
                 KPGQAPRLLIYGASTRATGIPARFSGSGSGTEFTLTIS 
               
               
                 278 
                 SLQSEDFAVYYCQQYNNWPPITFGQGTRLEIKR 
               
               
                   
               
               
                 SEQ 
                 DVVMTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQ 
               
               
                 ID 
                 QKPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTI 
               
               
                 279 
                 SRLEPEDFAVYYCQQYGSSGYTFGQGTKLEIKR 
               
               
                   
               
               
                 SEQ 
                 ETTLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQ 
               
               
                 ID 
                 QKPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTI 
               
               
                 280 
                 SRLEPEDFAVYYCQQYGSSFGQGTRLEIKR 
               
               
                   
               
               
                 SEQ 
                 EIVLTQSPSTLSASVGDRVTITCRASQSISSCLAWYQQ 
               
               
                 ID 
                 KPGKAPKLLIYAASTLQSGVPSRFSGSGSGTEFTLTIS 
               
               
                 281 
                 TLQPEDFATYYCQQLNSYPQTFGQGTKVDIKR 
               
               
                   
               
               
                 SEQ 
                 DIVMTHTPLSLSVTPGQPASISCKSSQSLLHSDGKTYL 
               
               
                 ID 
                 YWYLQKPGQPPQLLIYEVSNRFSGVPDRFSGSGSGTDF 
               
               
                 282 
                 TLKISRVEAEDVGVYYCMQSIQLPLTFGGGTKVEIKR 
               
               
                   
               
               
                 SEQ 
                 DVVMTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQ 
               
               
                 ID 
                 QKPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTI 
               
               
                 283 
                 SRLEPEDFAVYYCQQYNNWPLTFGGGTKLEIKR 
               
               
                   
               
               
                 SEQ 
                 DIQLTQSPDSLAVSLGERATINCTSSQSVLYSSNNKNY 
               
               
                 ID 
                 IAWYQQKPGQPPKLLIYWASTRESGVPDRFSGSGSGTD 
               
               
                 284 
                 FTLTISSLQAEDVAVYYCQQYYYIPRTFGQGTKVEIKR 
               
               
                   
               
               
                 SEQ 
                 DVVMTQSPLSLPVTPGEPASISCRSSQSLLHSNGYNYL 
               
               
                 ID 
                 DWYLQKPGQSPQLLIYLGSNRAPGVPDRFSGSGSGTDF 
               
               
                 285 
                 TLKISRVEAEDVGVYYCMQALQTRTFGQGTKLEIKR 
               
               
                   
               
               
                 SEQ 
                 ETTLTQSPGTLSLSPGERATLSCRASQSLTSSYLAWYQ 
               
               
                 ID 
                 QKPGQAPRLLIYRASSRATGIPDRFSGSGSGTDFTLTI 
               
               
                 286 
                 SRLEPEDFAVYYCQQYGSSPNTFGQGTRLEIKR 
               
               
                   
               
               
                 SEQ 
                 EIVLTQSPLSLPVTLGQPASISCRSSQSLVHSNGHTYL 
               
               
                 ID 
                 SWFQQRPGQSPRRLIYEVSNRDSGVPDRFSGSGSGTDF 
               
               
                 287 
                 TLRISRVEAEDVGVYYCLQGTHWPPLTVGGGTKVDIKR 
               
               
                   
               
               
                 SEQ 
                 DVVMTQSPATLSLSPGERATLSCRASQSVGSDLAWYQQ 
               
               
                 ID 
                 KPGQAPRLLIYRASTRAAGIPARFSGSGSGTDFTLTIS 
               
               
                 288 
                 RLEPEDFAVFYCQQYGRSPYTSGQGTKLEIKR 
               
               
                   
               
               
                 SEQ 
                 DIVMTHTPDSLAVSLGERATINCKSSQSVLYSSNNKNY 
               
               
                 ID 
                 LAWYQQKPGQPPKLLIYWASTRESGVPDRFSGSGSGTD 
               
               
                 289 
                 FTLTISSLQAEDVAVYYCQQYYSTPLTFGGGTKVEIKR 
               
               
                   
               
               
                 SEQ 
                 EIVMTQSPLSLSVTPGEPASISCRSSQSLLHSSGYNYL 
               
               
                 ID 
                 DWYLQKPGQSPQLLIYLGSTRASGVPDRFSGSGSGTDF 
               
               
                 290 
                 TLKISRVEAEDVGVYYCMQGLQIPLTFGGGTKVDIKR 
               
               
                   
               
               
                 SEQ 
                 DIVMTHTPLSLSVTPGQPASISCKSSQSLLHSDGKTYL 
               
               
                 ID 
                 YWYLQKPGQPPQLLIYEVSNRFSGVPDRFSGSGSGTDF 
               
               
                 291 
                 TLKISRVEAEDVGVYYCMQSIQLPWTFGQGTKVEIKR 
               
               
                   
               
               
                 SEQ 
                 ETTLTQSPATLSVSPGERATLSCRASQSVSSNLAWYQQ 
               
               
                 ID 
                 KPGQAPRLLIYGASTRATGIPARFSGSGSGTEFTLTIS 
               
               
                 292 
                 SLQSEDFAVYYCQQYNNWPRFGQGTRLEIKR 
               
               
                   
               
               
                 SEQ 
                 DVVMTQSPSTLSASVGDRVTITCRASQTINSWLAWYQQ 
               
               
                 ID 
                 KPGKAPKLLISRASRLESGVPSRFSGSASGTEYILTIN 
               
               
                 293 
                 SLQPDDFAMYFCHQYNSYSPTFGQGTKLEIKR 
               
               
                   
               
               
                 SEQ 
                 ETTLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQ 
               
               
                 ID 
                 QKPGQAPRLLIYGASSRATGIPARFSGSGSGTDFTLTI 
               
               
                 294 
                 SSLEPEDFAVYYCQQRYNWPITFGQGTRLEIKR 
               
               
                   
               
               
                 SEQ 
                 EIVLTQSPATLSLSPGETATLSCRASQTIGPKSFGWYQ 
               
               
                 ID 
                 QRPGQAPRLLIYDSNRATGIPARFSGSGSGTDFTLTIS 
               
               
                 295 
                 SLEPEDFAVYYCQQRSRWPLTFGPGTKVDIKR 
               
               
                   
               
               
                 SEQ 
                 DVVMTQSPLSLPVTLGQPASISCRSSQSLVYSDGNTYL 
               
               
                 ID 
                 YWFQQRAGQSPRRLIYKVSKRDSGVPDRFSGSGSGTDF 
               
               
                 296 
                 TLKISRVEAEDVGIYYCVQGRHWPYTLGQGTKLEIKR 
               
               
                   
               
               
                 SEQ 
                 EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQ 
               
               
                 ID 
                 QKPGQAPRLLIYDASNRATGIPARFSGSGSGTEFTLTI 
               
               
                 297 
                 SSLQPDDFATYYCQQYNSYSRTFGQGTKVDIKR 
               
               
                   
               
               
                 SEQ 
                 DVVMTQSPSTLSASVGDRVTITCRASQSITTWLAWSQQ 
               
               
                 ID 
                 QPGKAPKLLIYKASSLTSGVPSRFSGSGSGTEFTLTIS 
               
               
                 298 
                 SLQPDDFASYYCHHYNGASRMFGQGTKLEIKR 
               
               
                   
               
               
                 SEQ 
                 ETTLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQ 
               
               
                 ID 
                 KPGQAPRLLIYDASNRATGIPARFSGSGSGTDFTLTIS 
               
               
                 299 
                 SLEPEDFAVYYCQQRSNWPFFGQGTRLEIKR 
               
               
                   
               
               
                 SEQ 
                 ETTLTQSPATLTLSPGERVTLSCRASQSIGTYVAWYQQ 
               
               
                 ID 
                 KPGQAPRFLIYDSSNRATGIPARFSGSGSGTDFTLTIS 
               
               
                 300 
                 SLEPEDFAFYYCQQRAEWPLTFGQGTRLEIKR 
               
               
                   
               
               
                 SEQ 
                 DVVMTQSPGTLSLSPGERATLSCRASQSVNSGYLAWYQ 
               
               
                 ID 
                 QKPGQPPRLLISGVSTRATGIPDRFSGSGSGTDFTLTI 
               
               
                 301 
                 SRLEPEDFAVYYCQEYGNSAMYNFGQGTKLEIKR 
               
               
                   
               
               
                 SEQ 
                 ETTLTQSPATLSVSPGERATLSCRASQSVSSNLAWYQQ 
               
               
                 ID 
                 KPGQAPRLLIYGASTRATGIPARFSGSGSGTEFTLTIS 
               
               
                 302 
                 SLQSEDFAVYYCQQYNNWPPFTFGQGTRLEIKR 
               
               
                   
               
               
                 SEQ 
                 DVVMTQSPGTLSLSPGERATLSCRASQSVSSSYLGWYQ 
               
               
                 ID 
                 QKSGQAPRLLIYGASSRATDIPDRFSGSGSGTDFTLTI 
               
               
                 303 
                 SKLEAEDSAVYYCQQYGISPLAFGQGTKLEIKR 
               
               
                   
               
               
                 SEQ 
                 ETTLTQSPATLSVSPGERATLSCRASQSISNNLAWYQQ 
               
               
                 ID 
                 KPGQAPRLLIYGTSTRATGIPARFSGSGSGTEFTLTIS 
               
               
                 304 
                 SLQSEDFAVYYCQQYNFWPSITFGQGTRLEIKR 
               
               
                   
               
               
                 SEQ 
                 ETTLTQSPGTLSLSPGERATLSCRASQSVSSSSLAWYQ 
               
               
                 ID 
                 QKPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTI 
               
               
                 305 
                 SRLEPEDFAVYYCQQYGSSQTFGQGTRLEIKR 
               
               
                   
               
               
                 SEQ 
                 DVVMTQSPLSLPVSLGQPASISCRSNQSLVYSDGGTYL 
               
               
                 ID 
                 NWFQQRAGQSPRRLVYKVSNRDSGVPDRFSGSGSGTDF 
               
               
                 306 
                 TLRISRVEAEDVGVYYCMQGTHWPYTFGQGTKLEIKR 
               
               
                   
               
               
                 SEQ 
                 DIQLTQSPSSLSASVGDRVTVTCRASQSISSYLNWYQQ 
               
               
                 ID 
                 KPGKAPQLLIYDASNLETGVPSRFSGSGSGTDFTFTIS 
               
               
                 307 
                 SLQPEDFATYYCQQFDNVPVTFGGGTKVEIKR 
               
               
                   
               
               
                 SEQ 
                 EIVLTQSPLSLPVTLGQPASISCRSSQSLVYSDGNTYL 
               
               
                 ID 
                 NWFQQRPGQSPRRLIYKVSNRDSGVPDRFSGSGSGTDF 
               
               
                 308 
                 TLKISRVEAEDVGVYYCMQGTHWPRTFGQGTKLEIKR 
               
               
                   
               
               
                 SEQ 
                 DVVMTQSPATLSVSPGERATLSCRASQSVSSNLAWYQQ 
               
               
                 ID 
                 KPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTIN 
               
               
                 309 
                 RLEPEDFAVYYCQQYGSSSMYTFGQGTKLEIKR 
               
               
                   
               
               
                 SEQ 
                 DVVMTQSPSSLSASVGDSVAITCRASQSISNYLNWYQQ 
               
               
                 ID 
                 RPGKAPKLLIFAASSLQSGVPSRFSGSGSGTDFTLTIS 
               
               
                 310 
                 SLQPEDFATYSCQQSYITPWTFGQGTKLEIKR 
               
               
                   
               
               
                 SEQ 
                 DVVMTQSPGTLSLSPGERATLSCRASQSVSTLLAWYQQ 
               
               
                 ID 
                 KPGQAPRLLIYDASNRATGIPGRFSASGSGTDFSLTIS 
               
               
                 311 
                 SLETEDSAVYYCQHRYVWPFTFGGGTKLEIKR 
               
               
                   
               
               
                 SEQ 
                 DIQMTQSPSSLSASVGDRVTITCRASQGIRNDLGWYQQ 
               
               
                 ID 
                 KPGKAPKRLIYGASSLQSGVPSRFSGSGSGTEFTLTIR 
               
               
                 312 
                 SLQPEDFATYYCLQHNSYPRTFGQGTKVEIKR 
               
               
                   
               
               
                 SEQ 
                 DVVMTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQ 
               
               
                 ID 
                 KPGQAPRLLIYDASNRATGIPARFSGSGSGTDFTLTIS 
               
               
                 313 
                 SLEPEDFAVYYCQQRSNWPWTFGQGTKLEIKR 
               
               
                   
               
               
                 SEQ 
                 DVVMTQSPLSLPVTLGQAASISCRSSHSLTTTDGRTYV 
               
               
                 ID 
                 AWFQQRPGQSPRRLLYEVSKRDSGAPDRFSGSGSGTDF 
               
               
                 314 
                 TLKISRVEADDVGIYHCMQGTHGPHTFGQGTKLEIKR 
               
               
                   
               
               
                 SEQ 
                 ETTLTQSPATLSVSPGERATLSCRASQSVTSNLAWYQQ 
               
               
                 ID 
                 KPGQAPRLLIYGASNRATGIPARFSVSGSGTDFTLTIS 
               
               
                 315 
                 RLEPEDFAVYYCQQYGSPPPTTFGQGTRLEIKR 
               
               
                   
               
               
                 SEQ 
                 DVVMTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQ 
               
               
                 ID 
                 QKPGQAPRLLIYGASSRATGIPDRFSGSGSGTDFTLTI 
               
               
                 316 
                 SRLEPEDFAVYYCQQYGSSRRTFGQGTKLEIKR 
               
               
                   
               
               
                 SEQ 
                 ETTLTQSPGTLSLSPGERATLSCRASQSVFNNYLAWYQ 
               
               
                 ID 
                 QRPGQAPRLLIYGASSRATGIPDRFSGGGSGTDFTLTI 
               
               
                 317 
                 SRLEPEDFAVYCCQQYGSSPITFGQGTRLEIKR 
               
               
                   
               
               
                 SEQ 
                 EIVLTQSPATLSLSPGERATLSCRASQSVSSYLAWYQQ 
               
               
                 ID 
                 KPGQAPRLLIYDASNRATGIPARFSGSGSGTDFTLTIS 
               
               
                 318 
                 RLEPEDFAVYYCQQYGSSLRYTFGQGTKLEIKR 
               
               
                   
               
               
                 SEQ 
                 EIVLTQSPDSLAVSLGERATINCKSSQSVLYDSNSKNY 
               
               
                 ID 
                 LSWYQQKPGQPPKLLISWASTRGSGVPDRFSGSGSGTD 
               
               
                 319 
                 FTLTISSLQAEDVAVYYCQQFYGIPHFGQGTRLEIKR 
               
               
                   
               
               
                 SEQ 
                 DVVMTQSPATLSLSPGERATLSCRASQSVGTNLAWYQQ 
               
               
                 ID 
                 KPGQAPRLLIYDASNRATGIPARFSGSGSGTEFTLTIS 
               
               
                 320 
                 SLQSEDFAVYYCQQYNNWPPITFGGGTKLEIKR 
               
               
                   
               
               
                 SEQ 
                 DVVMTQSPLSLPVTLGQPASISCRSSQSLVYSDGNTYL 
               
               
                 ID 
                 SWLQQRPGQPPRLLIYKISNRFSGVPDRFSGSGAGTDF 
               
               
                 321 
                 TLKISRVEAEDVGVYYCMQGTQFPQTFGQGTKLEIKR 
               
               
                   
               
               
                 SEQ 
                 EIVLTQSPGTLSLSPGERATLSCRASQSVISRYLAWYQ 
               
               
                 ID 
                 QKPGQAPRLLIHGASTRATGIPDRFSGSGSGTDFTLTI 
               
               
                 322 
                 SRLEPEDFAVYYCQQYGSSPPYTFGQGTKVEIKR 
               
               
                   
               
               
                 SEQ 
                 DIQLTQSPSTLAASVGDRVTITCRASQSISSWLAWYQQ 
               
               
                 ID 
                 KPGKAPKVLIYKASSLESGVPSRFSGSGSGTEFTLTIS 
               
               
                 323 
                 SLQPDDFATYYCQQYNSYSGTFGQGTKVEIKR 
               
               
                   
               
               
                 SEQ 
                 DVVMTQSPAILSVSPGERATLSCRASQSVSSSLAWYQQ 
               
               
                 ID 
                 KPGQPPRLLIYGASTRATAIPARFSGSGSGTEFTLTIS 
               
               
                 324 
                 SLQSEDFAVYYCQRYDNWPPLFGQGTKLEIKR 
               
               
                   
               
            
           
         
       
     
     A VL amino acid sequence of the disclosure may be encoded by a polynucleotide shown in Table 5 below. 
     
       
         
           
               
             
               
                 TABLE 5 
               
             
            
               
                   
               
               
                 VL DNA Sequences 
               
            
           
           
               
               
            
               
                 SEQ 
                   
               
               
                 ID 
                 VL DNA Sequence 
               
               
                   
               
               
                 SEQ 
                 GAAACGACACTCACGCAGTCTCCAGCCACCCTATCTGTGTCTCTAGGAGAAAGAGCCACCC 
               
               
                 ID 
                 TTTCTTGCAGGGCCAGTCAGAGTATTGGCAGCAACTTAGTCTGGTACCAGCTGAAACCTGGC 
               
               
                 325 
                 CAGGGTCCCAGGCTCGTCATATATAGTGCAACCTCTAGGGCCACTGGAATCCCAGCCAGGT 
               
               
                   
                 TCAGCGGCAGTGGGTCTGGGACAGAGTTCATTCTCTCCATCAGCAACCTGCAGTCTGAAGAT 
               
               
                   
                 CTTGCAGTTTATTACTGTCAGCAGTATGGTAGTTCACCTCCGACCACCTTCGGCCAAGGGAC 
               
               
                   
                 ACGACTGGAGATTAAACGT 
               
               
                   
               
               
                 SEQ 
                 GAAATTGTGATGACACAGTCTCCAGCCACCCTGTCTTTGTCTCCAGGGGAAAGAGCCACCCT 
               
               
                 ID 
                 CTCCTGCAGGGCCAGTCAGAGTGTTAGCAGCAGCTACTTAGCCTGGTACCAGCAAAAACCT 
               
               
                 326 
                 GGCCGGGCTCCCAGGCTCCTCATCTATGGCGCATCCAACAGGGCCACAGGCATCCCAGACA 
               
               
                   
                 GGTTCAGTGGCAGTGGGTCTGGGACAGACTTCACTCTCATCATCAGCAGACTGGAGCCTGA 
               
               
                   
                 AGATTTTGCCTTGTATTACTGTCAGCAGTATGGAAGCTCACCGGGAACGTTCGGCCAAGGG 
               
               
                   
                 ACCAAAGTGGATATCAAACGT 
               
               
                   
               
               
                 SEQ 
                 GATGTTGTGATGACTCAGTCTCCAGCCACCCTGTCTTTGTCTCCAGGGGAAAGAGCCACCCT 
               
               
                 ID 
                 CTCCTGCAGGGCCAGTCAGAGTGTTAGCAGCTACTTAGCCTGGTACCAACAGAAACCTGGC 
               
               
                 327 
                 CAGGCTCCCAGGCTCCTCATCTATGATGCATCCAACAGGGCCACTGGCATCCCAGCCAGGTT 
               
               
                   
                 CAGTGGCAGTGGGTCTGGGACAGACTTCACTCTCACCATCAGCAGCCTAGAGCCTGAAGAT 
               
               
                   
                 TTTGCAGTTTATTACTGTCAGCAGCGTAGCAACTGGCCTCGGACGTTCGGCCAAGGGACCAA 
               
               
                   
                 GCTGGAGATCAAACGT 
               
               
                   
               
               
                 SEQ 
                 GAAATTGTGTTGACGCAGTCTCCAGACTCCCTGGCTGTGTCTCTGGGCGAGAGGGCCACCAT 
               
               
                 ID 
                 CACCTGCAAGTCCAGCCGGAATATTTTATACAGCGGCAACAATAAAAACTTCTTGGCTTGGT 
               
               
                 328 
                 ATCAGCACAAACCAGGACAGCCTCCTAAGTTGCTCATTTACTGGGCATCTACCCGGGAATCC 
               
               
                   
                 GGGGTCCCTGACCGATTTAGTGGCAGCGGGTCTGGGACAGATTTCACCCTCACCATCAATA 
               
               
                   
                 GCCTGGAAGCTGAAGATGCTGCAACGTATTACTGTCATCAGAGTAGTAGTTTACCTCACACT 
               
               
                   
                 TTCGGCCCTGGGACCAAAGTGGATATCAAACGT 
               
               
                   
               
               
                 SEQ 
                 GAAACGACACTCACGCAGTCTCCAGGCACCCTGTCTTTGTCTCCAGGGCAAAGAGCCACCC 
               
               
                 ID 
                 TCTCCTGCAGGGCCAGTGAGAGTGTTAGCAAGAGCTACTTACTCTGGTACCAGCAGAAACC 
               
               
                 329 
                 TGGCCAGGCTCCCAGACTCCTCATCTATGGTGCATCCACCAGGGCCAGTGGCATCCCAAAC 
               
               
                   
                 AGGTTCAGTGGCAGTGGGTCTGGGACAGACTTCACTCTCACCATCAGCAGACTGGAGCCTG 
               
               
                   
                 AAGATTCTGCAGTGTATTACTGTCAGCACTATGGCAGCTCTCGCACCTTCGGCCAAGGGACA 
               
               
                   
                 CGACTGGAGATTAAACGT 
               
               
                   
               
               
                 SEQ 
                 GAAACGACACTCACGCAGTCTCCAGGCACCCTGTCTTTGTCTCCAGGGGAAAGAGCCACCC 
               
               
                 ID 
                 TCTCCTGCAGGGCCAGTCAGAGTATTAGCAGCACCTACTTAGCCTGGTACCAGCAGAAACC 
               
               
                 330 
                 TGGCCAGGCTCCCAGGCTCCTCATCTATGGTGCATCCACCAGGGCCACTGGCATCCCAGACA 
               
               
                   
                 GGTTCAGTGGCAGTGGGTCTGGGACAGACTTCACTCTCAGCATCAGCAGACTGGAGCCTGA 
               
               
                   
                 AGATTTTGCAGTGTATTACTGTCAGCAGTATGGTAACTCACCTCCGGGAGCCACCTTCGGCC 
               
               
                   
                 AAGGGACACGACTGGAGATTAAACGT 
               
               
                   
               
               
                 SEQ 
                 GACATCCAGTTGACCCAGTCTCCTTCCTCCCTGTCTGCATCTGTGGGAGAAAGAGTCACCAT 
               
               
                 ID 
                 CACTTGCCGGTCCAGCCAGGCCCTGCGAAATGTTGTCGGCCTTGGCGATGATTTAGCCTGGT 
               
               
                 331 
                 ATCAACACACGCCAGGCAGCGCCCCCAAGATCCTGATCTACTCTACATCGACTTTACAAAGT 
               
               
                   
                 GGAGTCTCATCAAGATTCAGCGGCGGAAAGTCTGGGAGAGACTTCACTCTCACGATCGATC 
               
               
                   
                 GTCTGCAGCCTGGAGATTCTGCAACTTATTACTGTCTCCAGCACCATGATTTCCCTTTCACTT 
               
               
                   
                 TCGGCCCTGGGACCAAGGTGGAAATCAAACGT 
               
               
                   
               
               
                 SEQ 
                 GATGTTGTGATGACTCAGTCTCCACTCTCCCTGCCCGTCACCCCTGGAGAGCCGGCCTCCAT 
               
               
                 ID 
                 CTCCTGCAGGTCTAGTCAGAGCCTCCTGAATAGTAATGGATACAACTATTTGGAGTGGTACC 
               
               
                 332 
                 TGCAGAAGCCGGGGCAGTCTCCACAGCTCCTGATCTATTTGGGTTCTAATCGGGCCTCCGGG 
               
               
                   
                 GTCCCTGACAGGTTCAGTGGCAGTGGATCAGGCACAGATTTTACACTGAAAATCAGCAGAG 
               
               
                   
                 TGGAGGCTGACGATGCTGGTGTTTATTACTGCATGCAGTCTCTACAAACTCCTCTCACTTTC 
               
               
                   
                 GGCGGTGGGACCAAGCTGGAGATCAAACGT 
               
               
                   
               
               
                 SEQ 
                 GAAACGACACTCACGCAGTCTCCAGGCACCCTGTCTTTGTCTCCAGGGGAAAGAGCCACCC 
               
               
                 ID 
                 TCTCCTGCAGGGCCAGTCAGAGTGTTAGCAGCAGCTACTTAGCCTGGTACCAGCAGAAACC 
               
               
                 333 
                 TGGCCAGGCTCCCAGGCTCCTCATCTATGGTGCATCCAGCAGGGCCACTGGCATCCCAGAC 
               
               
                   
                 AGGTTCAGTGGCAGTGGGTCTGGGACAGACTTCACTCTCACCATCAGCAGACTGGAGCCTG 
               
               
                   
                 AAGATTTTGCAGTGTATTACTGTCAGCAGTATGGTAGCTCACCCCGGATCACCTTCGGCCAA 
               
               
                   
                 GGGACACGACTGGAGATTAAACGT 
               
               
                   
               
               
                 SEQ 
                 GATGTTGTGATGACTCAGTCTCCAGCCACCCTGTCTGTGTCTCCAGGGGAAAGAGCCACCCT 
               
               
                 ID 
                 CTCCTGCAGGGCCAGTCAGAGTGTTAGCAGCAACTTAGCCTGGTACCAGCAGAAACCTGGC 
               
               
                 334 
                 CAGGCTCCCAGGCTCCTCATCTATGGTGCATCCACCAGGGCCACTGGTATCCCAGCCAGGTT 
               
               
                   
                 CAGTGGCAGTGGGTCTGGGACAGAGTTCACTCTCACCATCAGCAGCCTGCAGTCTGAAGAT 
               
               
                   
                 TTTGCAGTTTATTACTGTCAGCAGTATAATAACTGGCCTCCTATGTACACTTTTGGCCAGGG 
               
               
                   
                 GACCAAGCTGGAGATCAAACGT 
               
               
                   
               
               
                 SEQ 
                 GATGTTGTGATGACTCAGTCTCCAGCCACCCTGTCTGTGTCTCCAGGGGAAAGAGTCACACT 
               
               
                 ID 
                 CTCCTGCAGGGCCAGTCAGAGTGTTAGAGACAACGTAGGTTGGTACAAGCAGAAACCTGGC 
               
               
                 335 
                 CAACCTCCCAGGCTCGTCATCTATGGTGCATCCACCAGGGCCACTGGTATCCCAGCCAGGAT 
               
               
                   
                 CAGTGGCAGTGGGTCTGGGACAGAGTTCACTCTCACCATCAGCAGCCTGCAGTCTGAAGAT 
               
               
                   
                 TTTGCAGTTTATTACTGTCAGCAGTTTAATAATTGGCCTTACACTTTTGGCCAGGGGACCAA 
               
               
                   
                 GCTGGAGATCAAACGT 
               
               
                   
               
               
                 SEQ 
                 GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCACCAT 
               
               
                 ID 
                 CACTTGCCGGGCAAGTCAGAGCATTAGCAGCTATTTAAATTGGTATCAGCAGAAACCAGGG 
               
               
                 336 
                 AAAGCCCCTAACCTCCTGATCTATGCTGCATCCAGTTTGCACACTGGGGTCCCATCAAGGTT 
               
               
                   
                 CAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAACCTGAAGATT 
               
               
                   
                 TTGCAACTTACTACTGTCAACAGAGTTACAGTATTCCTCGAACGTTCGGCCAAGGGACCAAG 
               
               
                   
                 GTGGAAATCAAACGT 
               
               
                   
               
               
                 SEQ 
                 GATGTTGTGATGACTCAGTCTCCAGCCACCCTGTCTGTGACTCCAGGGGAAAGGGCCACCCT 
               
               
                 ID 
                 CTCCTGCAGGGCCAGTCAAAGTGTTAACAGCAACGTAGCCTGGTACCAGCAGAAACCTGGC 
               
               
                 337 
                 CAGGCTCCCAGGCTCCTCATCTATGATGTATCCACCAGGGCCACTGATATCCCAGCCAGGTT 
               
               
                   
                 CAGTGGCAGTGGGTCTGGGACAGACTTCACTCTCACCATCAGCAGACTTGACCCTGAAGAT 
               
               
                   
                 TTTGCAGTGTATTACTGTCAGCAGTGTGCTAGCTCACCTCCTGTCACTTTCGGCGGAGGGAC 
               
               
                   
                 CAAGCTGGAGATCAAACGT 
               
               
                   
               
               
                 SEQ 
                 GAAATTGTGATGACGCAGTCTCCAGCCACCCTGTCTTTGTCTCCAGGGGAAAGAGCCACCCT 
               
               
                 ID 
                 CTCCTGCGGGGCCAGTCAGAGTGTTAGCAGCAGCTACTTAGCCTGGTACCAGCAGAAACCT 
               
               
                 338 
                 GGCCTGGCGCCCAGGCTCCTCATCTATGATGCATCCAGCAGGGCCACTGGCATCCCAGACA 
               
               
                   
                 GGTTCAGTGGCAGTGGGTCTGGGACAGACTTCACTCTCACCATCAGCAGACTGGAGCCTGA 
               
               
                   
                 AGATTTTGCAGTGTATTACTGTCAGCAGTATGGTAGCTCACCTCGGGTCACTTTCGGCGGAG 
               
               
                   
                 GGACCAAAGTGGATATCAAACGT 
               
               
                   
               
               
                 SEQ 
                 GATGTTGTGATGACTCAGTCTCCAGGCACCCTGTCTTTGTCTCCAGGGGAAAGAGCCACCCT 
               
               
                 ID 
                 CTCCTGCAGGGCCAGTCAGAGTGTTAGCAGCAGCGCCTTAGCCTGGTTCCAGCAGAAACCT 
               
               
                 339 
                 GGCCAGGCTCCCAGGCTCCTCATCTATGATTCATCCAGCAGGGCCACTGGCATCCCAGACA 
               
               
                   
                 GCTTCAGCGGCAGTGGATCTGGGACAGAATTCACACTCACAATCAGTAGCCTGCAGCCTGA 
               
               
                   
                 AGATTTTGCAACTTATTACTGTCAACAGTTTAATACCTACCCCAACACTTTTGGCCAGGGGA 
               
               
                   
                 CCAAGCTGGAGATCAAACGT 
               
               
                   
               
               
                 SEQ 
                 GACATCCAGATGACCCAGTCTCCACTCTCCCTGCCCGTCACCCCTGGAGAGCCGGCCTCCAT 
               
               
                 ID 
                 CTCCTGCAGGTCTAGTCAGAGCCTCCTGCATAGTAATGGATACAACTATTTGGATTGGTTCC 
               
               
                 340 
                 TGCAGAAGCCAGGGCAGTCTCCACGGCTCCTGATCTATATGGGTTCTAGTCGGGCCTCCGGG 
               
               
                   
                 GTCCCTGAGAGGTTCAGTGGCAGTGGATCAGGCACAGATTTTACACTGAAAATCAGCAGAG 
               
               
                   
                 TGGAGGCTGAGGATGTTGGGGTCTATTACTGCATGCAAACTTTACACACTGTCACTTTCGGC 
               
               
                   
                 GGCGGGACCAAGGTGGAAATCAAACGT 
               
               
                   
               
               
                 SEQ 
                 GAAACGACACTCACGCAGTCTCCAGGCACCCTGTCTTTGTCTCCAGGGGAAAGAGCCACCC 
               
               
                 ID 
                 TCTCCTGCAGGGCCAGTCAGAGTGTTAGCAGCAGCTACTTAGCCTGGTACCAGCAGAAACC 
               
               
                 341 
                 TGGCCAGGCTCCCAGGCTCCTCATCTATGGTGCATCCAGCAGGGCCACTGGCATCCCAGAC 
               
               
                   
                 AGGTTCAGTGGCAGTGGGTCTGGGACAGACTTCACTCTCACCATCAGCAGACTGGAGCCTG 
               
               
                   
                 AAGATTTTGCAGTGTATTACTGTCAGCAGTATGGTAGCTCACTCCTCTTCGGCCAAGGGACA 
               
               
                   
                 CGACTGGAGATTAAACGT 
               
               
                   
               
               
                 SEQ 
                 GACATCCAGTTGACCCAGTCTCCATCCTTCCTGTCTGCATCTGTTGGAGACAGAGTCACCAT 
               
               
                 ID 
                 CACTTGCCGGGCCAGTCAGGGCATTAGCAGTTCTTTGGCCTGGTATCAGCAAAAGCCAGGG 
               
               
                 342 
                 AAAGCCCCTAAGCTCCTGATCTATGCTGCATCCACTTTGCAAAGTGGGGTCCCATCAAGGTT 
               
               
                   
                 CAGTGGAAGTGGATCTGGGACAGATTTTACTTTCACCATCAGCAGCCTGCAGCCTGAAGAT 
               
               
                   
                 ATTGCAACATATTACTGTCAACAGTATGATAATCTCCCTCCTCTCACTTTCGGCGGAGGGAC 
               
               
                   
                 CAAGGTGGAAATCAAACGT 
               
               
                   
               
               
                 SEQ 
                 GATGTTGTGATGACTCAGTCTCCACTCTCCCTGCCCGTCACCCCTGGAGAGCCGGCCTCCAT 
               
               
                 ID 
                 CTCCTGCAGGTCTAGTCAGAGCCTCCTGCATAGTAATGGATACAACTATTTGGATTGGTACC 
               
               
                 343 
                 TGCAGAAGCCAGGGCAGTCTCCACAGCTCCTGATCTATTTGGGTTCTAATCGGGCCTCCGGG 
               
               
                   
                 GTCCCTGACAGGTTCAGTGGCAGTGGATCAGGCACAGATTTCACAGTGAAAATCAGCAGAG 
               
               
                   
                 TGGAGGCTGAGGATGTTGGGGTTTATTACTGCATGCAAGCTCTACAAACTCCGTACACTTTT 
               
               
                   
                 GGCCAGGGGACCAAGCTGGAGATCAAACGT 
               
               
                   
               
               
                 SEQ 
                 GAAATTGTGTTGACGCAGTCTCCACTCTCCCTGCCCGTCACCCTTGGACAGCCGGCCTCCAT 
               
               
                 ID 
                 CTCCTGCAGGTCTTGTCAAAGCCTCGTATACAGTGATGGCAACACCTACTTGAATTGCTTTC 
               
               
                 344 
                 AGCAGAGGCCAGGCCAATCTCCAAGGCGCCTAATTTATAAGGTTTCTAACCGGGACTCTGG 
               
               
                   
                 GGTCCCAGACAGATTCAGCGGCAGTGGGTCAGGCACAGATTTTACACTGGAAATCAGCAGA 
               
               
                   
                 GTGGAGGCTGAGGATGTTGGGATTTATTTCTGCATGCAAGGTCTACAAACTCCATTCACTTT 
               
               
                   
                 CGGCCCTGGGACCAAAGTGGATATCAAACGT 
               
               
                   
               
               
                 SEQ 
                 GATGTTGTGATGACTCAGTCTCCAGGCACCCTGTCTTTGTCTCCAGGGGAAAGAGCCACCCT 
               
               
                 ID 
                 CTCCTGCAGGGCCAGTCAGAGTGTTAGCAGCAGCTACTTAGCCTGGTACCAGCAGAAACCT 
               
               
                 345 
                 GGCCAGGCTCCCAGGCTCCTCATCTATGGTGCATCCAGCAGGGCCACTGGCATCCCAGACA 
               
               
                   
                 GGTTCAGTGGCAGTGGGTCTGGGACAGACTTCACTCTCACCATCAGCAGACTGGAGCCTGA 
               
               
                   
                 AGATTTTGCAGTGTATTACTGTCAGCAGTATGGTAGCTCACCTGCGCTCACTTTCGGCGGAG 
               
               
                   
                 GGACCAAGCTGGAGATCAAACGT 
               
               
                   
               
               
                 SEQ 
                 GAAATTGTGATGACGCAGTCTCCACTCTCCCTGCCCGTCACCCCTGGAGAGCCGGCCTCCAT 
               
               
                 ID 
                 CTCCTGCAGGTCTAGTCAGAGCCTCCTGCATAGTAATGGATACAACTATTTGGATTGGTACC 
               
               
                 346 
                 TGCAGAAGCCAGGGCAGTCTCCACAGCTCCTGATCTATTTGGGTTCTACTCGGGCCTCCGGG 
               
               
                   
                 GTCCCTGACAGGTTCAGTGGCAGTGGATCAGGCACAGACTTTACACTGAAAATCAGCAGAG 
               
               
                   
                 CGGAGGCTGAGGATGTTGGGGTTTATTACTGCATGCAAGCTCTACACACTCCGTGGACGTTC 
               
               
                   
                 GGCCTAGGGACCAAAGTGGATATCAAACGT 
               
               
                   
               
               
                 SEQ 
                 GACATCCAGATGACCCAGTCTCCAGCCACCCTGTCTGTGTCTCCAGGGGAAAGGGCCACCC 
               
               
                 ID 
                 TCTTTTGCCGGGCCAGTGAAGGTCTTACCACCAACTTAGCCTGGTACCAGCACAAACCTGGC 
               
               
                 347 
                 CAGGCTCCCAGGCTCCTCATCTATGCTGCCTCCACCAGGGCCACTGGTGTCCCAGCCAGGTT 
               
               
                   
                 CAGTGGCAGTGGGTCTGGGACAGACTTCACTCTCACCATCAGCAGCCTGCAGTCTGAAGAT 
               
               
                   
                 TCCGCAGTTTATTACTGTCAGCAGTATAATCACTGGCCTCTCTACACTTTTGGCCAGGGGAC 
               
               
                   
                 CAAGGTGGAAATCAAACGT 
               
               
                   
               
               
                 SEQ 
                 GACATCCAGTTGACCCAGTCTCCTTCCACCCTGTCTTTGTCTCCAGGGGAAAGAGCCACCCT 
               
               
                 ID 
                 CTCCTGCAGGGCCAGTCAGAGTGTTAGCAGCTACTTAGCCTGGTACCAACAGAAATCTGGC 
               
               
                 348 
                 CAGGCTCCCAGGCTCCTCATCTATGATGCATCCAACAGGGCCACTGGCATCCCAGCCAGGTT 
               
               
                   
                 CAGTGGCAGTGGGTCTGGGACAGACTTCACTCTCACCATCAGCAGCCTAGAGCCTGAAGAT 
               
               
                   
                 TTTGCAGTTTATTACTGTCAGCAGGGTAGCAACTGGCCGCTCACTTTCGGCGGAGGGACCAA 
               
               
                   
                 GGTGGAAATCAAACGT 
               
               
                   
               
               
                 SEQ 
                 GATATTGTGATGACCCACACTCCACTCTCCTCACCTGTCACCCTTGGACAGCCGGCCTCCAT 
               
               
                 ID 
                 CTCCTGCAGGTCTAGTCAAAGCCTCGAACACACTGATGGAAACACCTACTTAAGTTGGCTTC 
               
               
                 349 
                 ACCAGAGGCCAGGCCAGCCCCCAAGACTGTTAATTTATAAGGTTTCTACCCGGTTCTCTGGG 
               
               
                   
                 GTCCCAGACAGATTCAGTGGCAGTGGGGCAGGGACAGATTTCACACTGAAAATCAGCAGGG 
               
               
                   
                 TGGAGGCTGAGGATGTCGGCGTTTATTACTGCGTGCAGGCTACACACTATCCTCGGACGTTC 
               
               
                   
                 GGCCATGGGACCAAGGTGGAGATCAAACGT 
               
               
                   
               
               
                 SEQ 
                 GAAATTGTGCTGACTCAGTCTCCAGGCACCCTGTCCTTGTCTCCAGGGGAAAGAGCCACCCT 
               
               
                 ID 
                 CTCCTGCAGGGCCAGTCAGAGTATTAGCGGCAGTTACTTAGCCTGGTACCAGCAGAAACGT 
               
               
                 350 
                 GGCCAGGCTCCCAGGCTCCTCATCTATGATGCGTCCAGCAGGGCCGAAGGCATCCCAGACA 
               
               
                   
                 GGTTCATTGGCAGTGGGTCTGGGACAGACTTCACTCTCACCATCAGCAGACTGGAGCCTGA 
               
               
                   
                 AGACTTTGCTATGTATTACTGTCAGCAGTATGGTAGCTCACCAATATTCACTTTCGGCCCTG 
               
               
                   
                 GGACCAAAGTGGATATCAAACGT 
               
               
                   
               
               
                 SEQ 
                 GAAATTGTGCTGACTCAGTCTCCAGACTCCCTGCCCGTCACCCCTGGAGAGCCGGCCTCCAT 
               
               
                 ID 
                 CTCCTGCAGGTCTAGTCAGAGCCTCCTGCATAGTAATGGAAACAACTATTTGGATTGGTACC 
               
               
                 351 
                 TGCAGAAGCCAGGGCAGTCTCCACAGCTCCTGATCTATTTGGGTTCTAATCGGGCCTCCGGG 
               
               
                   
                 GTCCCTGACAGGTTCAGTGGCAGTGGATCAGGCACAGATTTTACACTGAAACTCAGCAGAG 
               
               
                   
                 TGGAGGCTGAGGATGTTGGGGTTTATTACTGCATGCAAGGTCTACAAATCCCTATCACTTTC 
               
               
                   
                 GGCCCTGGGACCAAAGTGGATATCAAACGT 
               
               
                   
               
               
                 SEQ 
                 GACATCCAGATGACCCAGTCTCCATCTTCTGTGTCTGCATCTGTGGGAGACAGAGTCACCAT 
               
               
                 ID 
                 CACTTGTCGGGCGAGTCAGAACATTCGCCACTGGTTAGTCTGGTATCAGCAAAAATTAGGG 
               
               
                 352 
                 CAAGCCCCTAAACTCCTGATCTATGCTGCGTCCAATTTGCAAAGTGGGGTCCCGTCAAGGTT 
               
               
                   
                 CAGCGGCAGTGGATCTGGGACAGAATTCACTCTCACAATCAACAGCCTGCAGGCTGAAGAT 
               
               
                   
                 TTTGCAACCTATTACTGTCTACAGCATAACAGTTACCCGTGGACGTTCGGCCAAGGGACCAA 
               
               
                   
                 GGTGGAAATCAAACGT 
               
               
                   
               
               
                 SEQ 
                 GAAATTGTGTTGACGCAGTCTCCAGACTTTCAGTCTGTGACTCCAAAGCAGAAAGTCACCAT 
               
               
                 ID 
                 CACCTGCCGGGCCAGTCAGAGCATTGGTGGTAGCTTACACTGGTACCAGCAGAAACCAGGT 
               
               
                 353 
                 CAGTCTCCAAAGCTCATCATCAAGTATGCTTCCCAGTCCTTCTCAGGGGTCCCCTCGAGGTT 
               
               
                   
                 CAGTGGCAGTGGATCTGGGACAGATTTCACCCTCACCATCGATAGCCTGGAGGCTGAAGAT 
               
               
                   
                 GCTGCAACGTACTATTGTCATCAGAGTATCAGTTTACCGCTCACTTTCGGCGGAGGGACCAA 
               
               
                   
                 AGTGGATATCAAACGT 
               
               
                   
               
               
                 SEQ 
                 GAAACGACACTCACGCAGTCTCCAGGCACCCTGTCTTTGTCTCCAGGGGAAGGAGCCACCC 
               
               
                 ID 
                 TCTCCTGCAGGGCCAGTCAGAGTGTTACCAGCAACTACTTAGCCTGGTACCAGCAGAAACC 
               
               
                 354 
                 TGGCCAGGCTCCCAGGCTCCTCATCTATGGTGCATCCTACAGGGCCACTGGCATCCCTGACA 
               
               
                   
                 GGTTCAGCGGCAGTGGGTCTGGGACAGACTTCACTCTCACCATCAGCAGACTGGAGCCTGA 
               
               
                   
                 AGATTTTGCAGTGTATTACTGTCAGCAGTATGCTAGCTCAGTCACCTTCGGCCAAGGGACAC 
               
               
                   
                 GACTGGAGATTAAACGT 
               
               
                   
               
               
                 SEQ 
                 GATGTTGTGATGACTCAGTCTCCAGCCACCCTGTCTGTGTCTCCAGGGGAAAGAGCCACCCT 
               
               
                 ID 
                 CTCCTGCAGGGCCAGTCAGAGTATTAGCAGCAACTTAGCCTGGTACCAGCAGAAACCTGGC 
               
               
                 355 
                 CAGGCTCCCAGGCTCCTCATCTATGGTGCCTCCACCAGGGCCACTGGTATCCCAGCCAGGTT 
               
               
                   
                 CAGTGGCAGTGGGTCTGGGACAGAGTTCACTCTCACCATCAGCAGCCTGCAGTCTGAAGAT 
               
               
                   
                 TTTGCAGTTTATTACTGTCAGCAGTATAATAACTGGCCTAGAACGTTCGGCCAAGGGACCAA 
               
               
                   
                 GCTGGAGATCAAACGT 
               
               
                   
               
               
                 SEQ 
                 GACATCCAGTTGACCCAGTCTCCAGACTCCCTGGCTGTGTCTCTGGGCGAGAGGGCCACCAT 
               
               
                 ID 
                 CAACTGCAAGTCCAGCCAGAGTGTTTTATACAGCTCCAACAATAAGAACTACTTAGCTTGGT 
               
               
                 356 
                 ACCAGCAGAAACCAGGACAGCCTCCTAAGCTGCTCATTTACTGGGCATCTGCCCGGGAATC 
               
               
                   
                 CGGGGTCCCTGACCGATTCAGTGGCAGCGGGTCTGGGACAGATTTCACTCTCACCATCAAC 
               
               
                   
                 AGCCTGCAGGCTGAAGATGTGGCAGTTTATTACTGTCAGCAATTTTATAGTCCTCCTCGGAC 
               
               
                   
                 GTTCGGCCAAGGGACCAAGGTGGAAATCAAACGT 
               
               
                   
               
               
                 SEQ 
                 GAAATTGTGTTGACACAGTCTCCAGGCACCCTGTCTTTGTCTCCAGGGGAAAGAGCCACCCT 
               
               
                 ID 
                 CTCCTGCAGGGCCAGTCAGAGTGTTAGCAGCAGCTACTTAGCCTGGTACCAGCAGAAACCT 
               
               
                 357 
                 GGCCAGGCTCCCAGGCTCCTCATCTATGGTGCATCCAGCAGGGCCACTGGCATCCCAGACA 
               
               
                   
                 GGTTCAGTGGCAGTGGGTCTGGGACAGACTTCACTCTCACCATCAGCAGACTGGAGCCTGA 
               
               
                   
                 AGATTTTGCAGTGTATTACTGTCAGCAGTATGGTAGCTCACCCCCGGGCACTTTCGGCGGAG 
               
               
                   
                 GGACCAAAGTGGATATCAAACGT 
               
               
                   
               
               
                 SEQ 
                 GAAATTGTGCTGACTCAGTCTCCAGGCACCCTGTCTTTGTCTCCAGGGGAAAGAGCCACCCT 
               
               
                 ID 
                 CTCCTGCAGGGCCAGTCAGAGTTTAAGTACCAACTTAGCCTGGTACCAGCAGAAACCTGGC 
               
               
                 358 
                 CAGGCTCCCAGGCTCCTCATCTATGGTGCATCCACCAGGGCCACTGGTATCCCAGCCAGGTT 
               
               
                   
                 CAGTGGCAGTGGGTCTGGCACAGAGTTCACTCTCACCATCACCAGCCTGCAGTCTGAAGATT 
               
               
                   
                 TTGCAGTTTATTACTGTCAGCAGTATCATAACTGGCCTCCGTACACTTTTGGCCAGGGGACC 
               
               
                   
                 AAGGTGGAGATCAAACGT 
               
               
                   
               
               
                 SEQ 
                 GACATCCAGATGACCCAGTCTCCTTCCACCCTGTCTGCATCTGTAGGAGACAGAGTCACCAT 
               
               
                 ID 
                 CACTTGCCGGGCCAGTCAGAGTATTAGTAGCTGGTTGGCCTGGTATCAGCAGAAACCAGGG 
               
               
                 359 
                 AAAGCCCCTAAGCTCCTGATCTATAAGGCGTCTAGTTTAGAAAGTGGGGTCCCATCAAGGTT 
               
               
                   
                 CAGCGGCAGTGGATCTGGGACAGAATTCACTCTCACCATCAGCAGCCTGCAGCCTGATGAT 
               
               
                   
                 TTTGCAACTTATTACTGCCAACAGTATAATAGTTATTGGACGTTCGGCCAAGGGACCAAGGT 
               
               
                   
                 GGAAATCAAACGT 
               
               
                   
               
               
                 SEQ 
                 GAAACGACACTCACGCAGTCTCCAGGCACCCTGTCTTTGTCTCCAGGGGAAGGCGCCACCC 
               
               
                 ID 
                 TCTCCTGCAGGGCCAGTCACAGTGTTGGCGCCAACTACATAGCCTGGTACCAGCAGAAACC 
               
               
                 360 
                 TGGCCAGGCTCCCAGGCTCCTTATCCATACTGCATCCAAAAGGGCCACTGGCGTCCCAGAG 
               
               
                   
                 AGGTTCAGTGGCAGTGGGTCTGGGACAGACTTCACTCTCAGTATCAGCAGACTGGAGCCTG 
               
               
                   
                 AAGACTTTGCCGTGTATCACTGTCAGCAGTATGCTGCCGCACCGATTACCTTCGGCCAAGGG 
               
               
                   
                 ACACGACTGGAGATTAAACGT 
               
               
                   
               
               
                 SEQ 
                 GAAATTGTGATGACACAGTCTCCATCCTCCCTGTCTGCATCTGTGGGGGACAGAGTCATCAT 
               
               
                 ID 
                 CACTTGCCGGGCGAGTCAGGGCATTGCCAATTATTTAGCCTGGTATCAGCAGAAACCAGGG 
               
               
                 361 
                 AAAGGTCCTAAACTCCTGATCTATGCTTCATCTACTTTGCAATCAGGGGTCCCATCTCGGTT 
               
               
                   
                 CAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCGGCCTGCAGCCTGAAGAT 
               
               
                   
                 GTTGCAACTTATTACTGTCAGAAGTATAACAGTGTCCCTCTCACTTTCGGCGGAGGGACCAA 
               
               
                   
                 AGTGGATATCAAACGT 
               
               
                   
               
               
                 SEQ 
                 GATGTTGTGATGACTCAGTCTCCAGTCTCCCTGGCTGTGTCTCTGGGCGAGAGGGCCACCAT 
               
               
                 ID 
                 CAACTGCAAGTCCAGCCAGAGTGTTTTATACAGAACCAACAATAAGAACTACTTGGCTTGG 
               
               
                 362 
                 TATCAGCAGAAACCAGGACAGCCTCCTAAGTTGCTCATTTACTGGGCATCTACCCGGGAATC 
               
               
                   
                 CGGGGTCCCTGACCGATTCAGTGGCAGCGGGTCTGGGACAGATTTCACTCTCACCATCAGC 
               
               
                   
                 AGCCTGCAGCCTGAGGATGTGGCAGTGTACTACTGTCAGCAATATTACAATCTTCCTCGATC 
               
               
                   
                 TTTTGGCCAGGGGACCAAGCTGGAGATCAAACGT 
               
               
                   
               
               
                 SEQ 
                 GATATTGTGATGACCCACACTCCAGACTCCCTGGCTGTGTCTCTGGGCGAGAGGGCCACCAT 
               
               
                 ID 
                 CAACTGCAAGTCCAACCGGAGTGTTTTATACAGCCCCAACAATCAGAACTACTTAGGTTGGT 
               
               
                 363 
                 ACCAGCAGAAGCCAGGACAGCCTCCTAAGCTGCTCATTTACTGGGCATCTACCCGGGACTC 
               
               
                   
                 CGGGGCCCCTGACCGATTCAGTGGCAGCGGGTCTGGGACAGATTTCACTCTCACCATCAAC 
               
               
                   
                 AGCCTGCAGGCTGAAGATGTGGCAGTTTATTACTGTCAGCAATATGCAAGTACTCCATACAC 
               
               
                   
                 TTTTGGCCAGGGGACCAAGGTGGAGATCAAACGT 
               
               
                   
               
               
                 SEQ 
                 GATGTTGTGATGACTCAGTCTCCAGCCACCCTGTCTTTGTCTCCAGGGGAAAGAGCCACCCT 
               
               
                 ID 
                 CTCCTGCAGGGCCAGTGAGAGTGTTAATAGCAACTTCTTAGCCTGGTACCAGCAGAAACCT 
               
               
                 364 
                 GGCCAGGCTCCCAGGCTCCTCATCTATGCTGCATCCACCAGGGCCACTGGTATCCCAGCCAG 
               
               
                   
                 GTTCAGTGGCAGTGGGTCTGGGACAGAGTTCACTCTCATCATCACCAGCCTGCAGTCTGAAG 
               
               
                   
                 ATTTTGCAGTTTATTACTGTCAGCAGTATAATAACTGGCCGCTCACTTTCGGCGGAGGGACC 
               
               
                   
                 AAGCTGGAGATCAAACGT 
               
               
                   
               
               
                 SEQ 
                 GATGTTGTGATGACTCAGTCTCCAGCCACCCTGTCTTTGTCTCCAGGGGAAAGAGCCACCCT 
               
               
                 ID 
                 CTCCTGCAGGGCCAGTCAGAGTGTTAGCAGCTACTTAGCCTGGTACCAACAGAAACCTGGC 
               
               
                 365 
                 CAGGCTCCCAGGCTCCTCATCTATGATGCATCCAACAGGGCCACTGGCATCCCAGCCAGGTT 
               
               
                   
                 CAGTGGCAGTGGGTCTGGGACAGACTTCACTCTCACCATCAGCAGCCTAGAGCCTGAAGAT 
               
               
                   
                 TTTGCAGTTTATTACTGTCAGCAGCGTAGCAACTGGTCGCTCACTTTCGGCGGAGGGACCAA 
               
               
                   
                 GCTGGAGATCAAACGT 
               
               
                   
               
               
                 SEQ 
                 GAAACGACACTCACGCAGTCTCCAGGCACCCTGTCTTTGTCTCCAGGGGAAAGAGCCACCC 
               
               
                 ID 
                 TCTCCTGCAGGGCCAGTCAGAGTGTTAGCAGCAGCTACTTAGCCTGGTACCAACAGAAACC 
               
               
                 366 
                 TGGCCAGGCTCCCAGGCTCCTCATCTATGGTGCTTCCACCAGGGCCACTGGCATCCCAGACA 
               
               
                   
                 GGTTCAGTGGCAGTGGGTCTGGGACGGACTTCACTCTCACCATCGGCAGACTGGAGCCTGA 
               
               
                   
                 AGATTTTGCAGTGTATTACTGTCAACACTATGGTCCCTCACGTCGGATCACCTTCGGCCAAG 
               
               
                   
                 GGACACGACTGGAGATTAAACGT 
               
               
                   
               
               
                 SEQ 
                 GAAACGACACTCACGCAGTCTCCAGACACCCTGTCTGTGTCTCCAGGGGGAAGAGCCACCC 
               
               
                 ID 
                 TCTCCTGTAGGGCCAGTCAGAGCATTGGGAGCAATTTAGCCTGGTACCAACAGAAACCTGG 
               
               
                 367 
                 CCAGTCTCCCAGGCTCCTCATCTATGATGCATCCACCAGGGCCACGGGAATCCCAGCCAGGT 
               
               
                   
                 TCAGTGGCAGTGGGTCTGGGACAGAATTCACTCTCACCATCAGCAGCCTGGAGTCTGAAGA 
               
               
                   
                 TTTTGTACTTTATTACTGTCAGCAGCATGGTGAATGGCCCACCTTCGGCCAAGGGACACGAC 
               
               
                   
                 TGGAGATTAAACGT 
               
               
                   
               
               
                 SEQ 
                 GATGTTGTGATGACTCAGTCTCCAGCCACCCTGTCTTTGTCTCCAGGGGAAAGAGCCACCCT 
               
               
                 ID 
                 CTCCTGCAGGGCCAGTCAGAGTGTCGGTAACTCCTTAGCCTGGTACCAGCAGAAGCCTGGC 
               
               
                 368 
                 CAGGCTCCCCGGCTCCTCATCTATGATGCATCCAACAGGGCCACTGGCATCCCAGCCCGGTT 
               
               
                   
                 CAGTGGCAGTGGGTCTGGGACAGACTTCACTCTCACCATCACCAGCCTAGAGCCTGAAGAT 
               
               
                   
                 TTTGCAATTTATTACTGTCAACAACGTGGCACCTGGCCTCCCCTCACTTTCGGCGGAGGGAC 
               
               
                   
                 CAAGCTGGAGATCAAACGT 
               
               
                   
               
               
                 SEQ 
                 GATGTTGTGATGACTCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACACAGTCACCAT 
               
               
                 ID 
                 CACTTGCCGGGCCAGTCAGAGTATAACTAACTGGTTGGCCTGGTATCAGCAGAAACCAGGG 
               
               
                 369 
                 AAAGCCCCCAAGCGCCTGATCTATGGTGCGTCCAGTTTGCAGAGTGGGGTCCCATCAAGGT 
               
               
                   
                 TCAGCGGCAGTGGATCTGGGACAGAATTCACTCTCACAATCAGCAGCCTGCAGCCTGAAGA 
               
               
                   
                 TTTTGCAACTTATTACTGTCAACAGTATACTAATTACCCTCGTACGTTCGGCCAAGGGACCA 
               
               
                   
                 AGCTGGAGATCAAACGT 
               
               
                   
               
               
                 SEQ 
                 GACATCCAGATGACCCAGTCTCCTTCCACCCTGTCTGCATCTGTAGGAGACAGAGTCACCAT 
               
               
                 ID 
                 CACTTGTCGGGCCAGGCAGAGCATCAGTAACCGGTTGGCCTGGTATCAGCAGAAACCAGGG 
               
               
                 370 
                 AGAGCCCCTAATGTCCTGATCTATAAGGCGTCTACTTTAGCAAATGGGGTCCCATCAAGGTT 
               
               
                   
                 CAGCGGCAGTGGATCTGGGACAGAATTCACTCTCACCATCAGCAGCCTGCAGCCTGATGAC 
               
               
                   
                 TTTGCAACTTATTACTGCCAACAGTATCAAAGTTACTGGACGTTCGGCCCAGGGACCAAGGT 
               
               
                   
                 GGAAATCAAACGT 
               
               
                   
               
               
                 SEQ 
                 GACATCCAGTTGACCCAGTCTCCAGCCACCCTGTCTTTGTCTCCAGGGGAAAGAGCCACCCT 
               
               
                 ID 
                 CTCCTGCAAGGCCAGTCAGAGTGTTAGTAGCTACTTAGCCTGGTACCAACAGAAACTTGGC 
               
               
                 371 
                 CAGGCTCCCAGGCTCCTCATCTATGATGCATCCAACAGGGCCACTGGCATCCCAGCCAGGTT 
               
               
                   
                 CAGTGCCAGTGGGTCTGGGACAGACTTCACTCTCACCATCAGCAGCCTGCAGCCTGAAGAT 
               
               
                   
                 GTTGCAACTTATTACTGTCAAAAGTATAACAGTCCCCCTCGGACGTTCGGCCAGGGGACCA 
               
               
                   
                 AGGTGGAAATCAAACGT 
               
               
                   
               
               
                 SEQ 
                 GAAACGACACTCACGCAGTCTCCAGGCACCCTGTCTTTGTCTCCAGGGGAAAGGGTCAGCC 
               
               
                 ID 
                 TTTCCTGCAGGGCCAGTCAGAATGTTTACAGCAATTTCTTAGCCTGGTATCAACAGAGACCT 
               
               
                 372 
                 GGCCAGGCTCCCAGTCTCCTCATCTATGGTGCCTCCAGCAGGGCCGCTGGCGTCCCAGACAG 
               
               
                   
                 GTTCAGTGGCAGTGGGTCTGGGACAGACTTCGCTCTCACCATCAGCAGAGTGGAGCCTGAA 
               
               
                   
                 GATTTTGCAGTCTATTACTGTCAACAATATGGAACCTCACCGATCACCTTCGGCCAAGGGAC 
               
               
                   
                 ACGACTGGAGATTAAACGT 
               
               
                   
               
               
                 SEQ 
                 GAAATTGTGCTGACTCAGTCTCCACGCTCCTCACCCGTCACCCTTGGACAGCCGGCCTCCAT 
               
               
                 ID 
                 CTCCTGTAGGTCTAGTCAAAGTCTCGAACACGGTGATGGAAACACGTACTTGAGTTGGCTTC 
               
               
                 373 
                 AGCAGAGGCCAGGCCAGCCTCCAAGACTCCTGATTTATAAGGTTTCTAACCGGTTGTCTGGG 
               
               
                   
                 GTCCCAGACAGATTCAGTGGCAGTGGGGCAGGGACTGATTTCACACTGAAAATCAGCAGGG 
               
               
                   
                 TGGAAGCTGAGGATGTCGGGGTTTATTACTGCATGCAAGGTATATACTGGCCTCGAACCTTC 
               
               
                   
                 GGCCAAGGGACACGACTGGAGATTAAACGT 
               
               
                   
               
               
                 SEQ 
                 GAAACGACACTCACGCAGTCTCCAGTCACCCTGTCTTTGTCTCCAGGGGACAGAGCCACCCT 
               
               
                 ID 
                 CTCTTGCAGGGCCAGTCAGAGTGTTAGCAGCACCTCCTTAGCCTGGTACCAGCACAAACCTG 
               
               
                 374 
                 GCCAGGCTCCCAGGCTCCTCATCTATGGTGCATCCAGGAGGGCCACTGGCATCCCAGACAG 
               
               
                   
                 GTTCAGTGGCAGTGGGTCTGGGACAGACTTCACTCTCACCATCAACAGACTGGAGCCTGAA 
               
               
                   
                 GATTTTGCAGTGTATTACTGTCAGCACTATGGTAGTTCACCTCCAATCACCTTCGGCCAAGG 
               
               
                   
                 GACACGACTGGAGATTAAACGT 
               
               
                   
               
               
                 SEQ 
                 GAAACGACACTCACGCAGTCTCCAGCCACCCTGTCTGTGTCTCCAGGGGAAAGAGCCACCC 
               
               
                 ID 
                 TCTCCTGCAGGGCCAGTCAGAGTGTTGGCAGCAAATTAGCCTGGTACCAGCAGAAACCTGG 
               
               
                 375 
                 CCAGGCTCCCAGGCTCCTCATCTATGGTGCATCCACCAGGGCCACTGGTGTCCCAGTCCGGT 
               
               
                   
                 TCAGTGGCAGTGGGTCTGGGACAGAATTCACTCTCACCATCAGCAGCCTGCAGTCTGAAGA 
               
               
                   
                 TTTTGCAGTTTATTACTGTCAGCAGTATAATAACTGGCCCCCGATCACCTTCGGCCAAGGGA 
               
               
                   
                 CACGACTGGAGATTAAACGT 
               
               
                   
               
               
                 SEQ 
                 GAAATTGTGTTGACGCAGTCTCCACTCTCCCTGCCCGTCACCCCTGGAGAGCCGGCCTCCAT 
               
               
                 ID 
                 CTCCTGCAGGTCTAGTCAGAGCCTCCTGCATAGTAATGGATACAACTATTTGGATTGGTACC 
               
               
                 376 
                 TGCAGAAGCCAGGGCAGTCTCCACAGCTCCTGATCTATTTGGGTTCTAATCGGGCCTCCGGG 
               
               
                   
                 GTCCCTGACAGGTTCAGTGGCAGTGGATCAGGCACAGATTTTACACTGAAAATCAGCAGAG 
               
               
                   
                 TGGAGGCTGAGGATGTTGGGGTGTATTACTGCATGCAAACTCTTCAAACTCCGCTCACTTTC 
               
               
                   
                 GGCGGAGGGACCAAAGTGGATATCAAACGT 
               
               
                   
               
               
                 SEQ 
                 GATGTTGTGATGACTCAGTCTCCAGACTCCCTGGCTGTGTCTCTGGGCGAGAGGGCCACCAT 
               
               
                 ID 
                 CAACTGCAAGTCCAGCCAGAGTGTTTTATACAGCTCCAACAATAAGAACTACTTAGCTTGGT 
               
               
                 377 
                 ACCAGCAGAAACCAGGACAGCCTCCTAAGCTGCTCATTTACTGGGCATCTACCCGGGAATC 
               
               
                   
                 CGGGGTCCCTGACCGATTCAGTGGCAGCGGGTCTGGGACAGATTTCACTCTCACCATCAGC 
               
               
                   
                 AGCCTGCAGGCTGAAGATGTGGCAGTTTATTACTGTCAGCAATATTATAGTAGTACTCCGTA 
               
               
                   
                 CACTTTTGGCCAGGGGACCAAGCTGGAGATCAAACGT 
               
               
                   
               
               
                 SEQ 
                 GATATTGTGATGACCCACACTCCCCTCTCTCTGTCCGTCACCCCTGGACAGCCGGCCTCCAT 
               
               
                 ID 
                 CTCCTGCAAGTCTAGTCAGAGCCTCCTGGGTGGTGATGGAAAGACCTATTTGTATTGGTACC 
               
               
                 378 
                 TGCAGAAGCCAGGCCAGCCTCCACAGCTCCTGCTCTATGAAGTTTCCAACCGATTCTCTGGA 
               
               
                   
                 GTGCCAGATAGGTTCAGTGGCAGCGGGGCAGCGACAGATTTCACACTGAAAATCAGCAGGG 
               
               
                   
                 TGGAAGCTGAGGATGTCGGGGTTTATTACTGCATGCAATCTACACAATTTCCGTGGACGTTC 
               
               
                   
                 GGCCAAGGGACCAAGGTGGAGATCAAACGT 
               
               
                   
               
               
                 SEQ 
                 GAAACGACACTCACGCAGTCTCCAGGCACCCTGTCTTTGTCTGCAGGGGAAAGAGCCACCC 
               
               
                 ID 
                 TCTCCTGCAGGGCCAGTCAGAGTGTTAGCAGCAGCTACTTAGCCTGGTACCAGCAGAAACC 
               
               
                 379 
                 TGGCCAGGCTCCCAGGCTCCTCATCTATGCTGCATCCTACAGGGCCACTGGCATCCCAGACA 
               
               
                   
                 GGTTCAGTGGCCGTGGGTCTGGGACAGAGTTCACTCTCACCATCAGCAGCCTGCAGTCTGA 
               
               
                   
                 AGATTTTGCAGTTTATTACTGTCAGCAGTATAATAACTGGCCTCCCATCACCTTCGGCCAAG 
               
               
                   
                 GGACACGACTGGAGATTAAACGT 
               
               
                   
               
               
                 SEQ 
                 GATGTTGTGATGACTCAGTCTCCAGCCACCCTGTCTGTGTCTCCAGGGGAAAGAGCCACCCT 
               
               
                 ID 
                 CTCCTGCAGGGCCAGTCAGAGTGTTAGCAGCAACTTAGCCTGGTACCAGCAGAAACCTGGC 
               
               
                 380 
                 CAGGCTCCCAGGCTCCTCATCTATGATGCATCCACCAGGGCCACTGGTATCCCAGCCAGGTT 
               
               
                   
                 CAGTGGCAGTGGGTCTGGGACAGAGTTCACTCTCACCATCAGCAGCCTGCAGTCTGAAGAT 
               
               
                   
                 TTTGCAGTTTATTACTGTCAGCACTATAATAACTGGCCTCATACCTTCGGCCAAGGGACCAA 
               
               
                   
                 GCTGGAGATCAAACGT 
               
               
                   
               
               
                 SEQ 
                 GAAACGACACTCACGCAGTCTCCAGGCACCCTGTCTTTGTCTCCAGGGGAAAGAGCCACCC 
               
               
                 ID 
                 TCTCCTGCAGGGCCAGTCAGAGTGTTAGCAGCAACTCCTTAGCCTGGTACCAGCAGAAACC 
               
               
                 381 
                 TGGCCAGGCTCCCAGGCTCCTCATCTATGGTGCATCCAGCAGGGCCTCTGGCATCCCAGACA 
               
               
                   
                 GGTTCAATGGCAGTGGGTCTGGGACAGACTTCACTCTCACCATCAATAGGCTGGAGCCTGA 
               
               
                   
                 AGACTTTGCAGTGTATTACTGTCAGCAGTATGGTAACTCACAGACCTTCGGCCAAGGGACA 
               
               
                   
                 CGACTGGAGATTAAACGT 
               
               
                   
               
               
                 SEQ 
                 GATGTTGTGATGACTCAGTCTCCAGCCACCCTGTCTGTGTCTCCAGGGGAAAGAGCCACCCT 
               
               
                 ID 
                 CTCCTGCAGGGCCAGTCAGAGTGTTAGCAGCAACTTAGCCTGGTACCAGCAGAAACCTGGC 
               
               
                 382 
                 CAGGCTCCCAGGCTCCTCATCTATGGTGCATCCACCAGGGCCACTGGTATCCCAGCCAGGTT 
               
               
                   
                 CAGTGGCAGTGGGTCTGGGACAGAGTTCACTCTCACCATCAGCAGCCTGCAGTCTGAAGAT 
               
               
                   
                 TTTGCAGTTTATTACTGTCAGCAGTATAATAACTGGCCCCGGACGTTCGGCCAAGGGACCAA 
               
               
                   
                 GCTGGAGATCAAACGT 
               
               
                   
               
               
                 SEQ 
                 GATGTTGTGATGACTCAGTCTCCACTCTCCCTGCCCGTCACCCTTGGACAGCCGGCCTCCAT 
               
               
                 ID 
                 CTCCTGCAGGTCTAGTCAAAGCCTCGTATACAGTGATGGAAACACCTACTTGAATTGGTTTC 
               
               
                 383 
                 AGCAGAGGCCAGGCCAATCTCCAAGGCGCCTAATTTATAAGGTTTCTAACCGGGACTCTGG 
               
               
                   
                 GGTCCCAGACAGATTCAGCGGCAGTGGGTCAGGCACTGATTTCACACTGAAAATCAGCAGG 
               
               
                   
                 GTGGAGGCTGAGGATGTTGGGGTTTATTACTGCATGCAAGGTACACATTGGCCTCGGACTTT 
               
               
                   
                 CGGCGGAGGGACCAAGCTGGAGATCAAACGT 
               
               
                   
               
               
                 SEQ 
                 GACATCCAGATGACCCAGTCTCCTTCCACCCTGTCTGCATCTGTAGGAGACAGAGTCACCAT 
               
               
                 ID 
                 CACTTGCCGGGCCAGTCAGAGTATTAGTAGGTGGTTGGCCTGGTATCAGCAGAAGCCAGGG 
               
               
                 384 
                 AAAGCCCCTAAGCTCCTGATCTATAAGGCGTCTACTATAAAAAGTGGGGTCCCATCAAGAT 
               
               
                   
                 TCAGCGCCAGTGGATCTGGGACAGAATTCACTCTCACCATCAGCAGCCTGCAGCCTGAAGA 
               
               
                   
                 TTTTGCAACTTATTACTGCCAACACTATAAAAGTGATTCCCGGACGTTCGGCCAAGGGACCA 
               
               
                   
                 AGGTGGAAATCAAACGT 
               
               
                   
               
               
                 SEQ 
                 GATGTTGTGATGACTCAGTCTCCATCCTCCCTCGCTGCATCTGTTGGAGACAGAATTACCAT 
               
               
                 ID 
                 CACTTGCCGGCCAAGTCAGGACATAGGCACTTATTTAAATTGGTATCAACAGAAGGCAGGG 
               
               
                 385 
                 GAAGCCCCTAAGCTCCTCATCTATGCTGCCTCCAATCTGCACAGTGGCGTCTCATCAAGGTT 
               
               
                   
                 CAGAGGCGTTGGGTCTGGGACACAATTCACTCTCACCATCAGCAGTCTGCAACCTGAGGAT 
               
               
                   
                 TTTGCAACTTACTACTGTCATCAGAGTTACGGTCCTCGGACATTCGGCCAAGGGACCAAGCT 
               
               
                   
                 GGAGATCAAACGT 
               
               
                   
               
               
                 SEQ 
                 GAAACGACACTCACGCAGTCTCCAGCCACCCTGTCTGTGTCTCCAGGGGAAAGAGCCACCC 
               
               
                 ID 
                 TCTCCTGCAGGGCCAGTCAGAGTGTTAGCAGCAACTTAGCCTGGTACCAGCAGAAACCTGG 
               
               
                 386 
                 CCAGGCTCCCAGGCTCCTCATCTATGGTGCATCCACCAGGGCCACTGGCATCCCAGCCAGGT 
               
               
                   
                 TCAGTGGCAGTGGGTCTGGGACAGAGTTCACTCTCACCATCAGCAGCCTGCAGTCTGAAGA 
               
               
                   
                 TTTTGCAGTTTATTACTGTCAGCAGTATAATAACTGGCCTCCGATCACCTTCGGCCAAGGGA 
               
               
                   
                 CACGACTGGAGATTAAACGT 
               
               
                   
               
               
                 SEQ 
                 GATGTTGTGATGACTCAGTCTCCAGGCACCCTGTCTTTGTCTCCAGGGGAAAGAGCCACCCT 
               
               
                 ID 
                 CTCCTGCAGGGCCAGTCAGAGTGTTAGCAGCAGCTACTTAGCCTGGTACCAGCAGAAACCT 
               
               
                 387 
                 GGCCAGGCTCCCAGGCTCCTCATCTATGGTGCATCCAGCAGGGCCACTGGCATCCCAGACA 
               
               
                   
                 GGTTCAGTGGCAGTGGGTCTGGGACAGACTTCACTCTCACCATCAGCAGACTGGAGCCTGA 
               
               
                   
                 AGATTTTGCAGTGTATTACTGTCAGCAGTATGGTAGCTCAGGGTACACTTTTGGCCAGGGGA 
               
               
                   
                 CCAAGCTGGAGATCAAACGT 
               
               
                   
               
               
                 SEQ 
                 GAAACGACACTCACGCAGTCTCCAGGCACCCTGTCTTTGTCTCCAGGGGAAAGAGCCACCC 
               
               
                 ID 
                 TCTCCTGCAGGGCCAGTCAGAGTGTTAGCAGCAGCTACTTAGCCTGGTACCAGCAGAAACC 
               
               
                 388 
                 TGGCCAGGCTCCCAGGCTCCTCATCTATGGTGCATCCAGCAGGGCCACTGGCATCCCAGAC 
               
               
                   
                 AGGTTCAGTGGCAGTGGGTCTGGGACAGACTTCACTCTCACCATCAGCAGACTGGAGCCTG 
               
               
                   
                 AAGATTTTGCAGTGTATTACTGTCAGCAGTATGGTAGCTCGTTCGGCCAAGGGACACGACTG 
               
               
                   
                 GAGATTAAACGT 
               
               
                   
               
               
                 SEQ 
                 GAAATTGTGTTGACACAGTCTCCTTCCACCCTGTCTGCATCTGTAGGGGACAGAGTCACCAT 
               
               
                 ID 
                 CACTTGCCGGGCCAGTCAGAGTATTAGTAGCTGCTTGGCCTGGTATCAGCAGAAACCAGGG 
               
               
                 389 
                 AAAGCCCCTAAGCTCCTGATCTATGCTGCATCCACTTTGCAAAGTGGGGTCCCATCAAGGTT 
               
               
                   
                 CAGCGGCAGTGGATCTGGGACAGAATTCACTCTCACAATCAGCACCCTGCAGCCTGAAGAT 
               
               
                   
                 TTTGCAACTTATTACTGTCAACAGCTTAATAGTTACCCTCAGACGTTCGGCCAAGGGACCAA 
               
               
                   
                 AGTGGATATCAAACGT 
               
               
                   
               
               
                 SEQ 
                 GATATTGTGATGACCCACACTCCACTCTCTCTGTCCGTCACCCCTGGACAGCCGGCCTCCAT 
               
               
                 ID 
                 CTCCTGCAAGTCTAGTCAGAGCCTCCTGCATAGTGATGGAAAGACCTATTTGTATTGGTACC 
               
               
                 390 
                 TGCAGAAGCCAGGCCAGCCTCCACAGCTCCTGATCTATGAAGTTTCCAACCGGTTCTCTGGA 
               
               
                   
                 GTGCCAGATAGGTTCAGTGGCAGCGGGTCAGGGACAGATTTCACACTGAAAATCAGCCGGG 
               
               
                   
                 TGGAGGCTGAGGATGTTGGGGTTTATTACTGCATGCAAAGTATACAGCTTCCGCTCACTTTC 
               
               
                   
                 GGCGGAGGGACCAAGGTGGAGATCAAACGT 
               
               
                   
               
               
                 SEQ 
                 GATGTTGTGATGACTCAGTCTCCAGGCACCCTGTCTTTGTCTCCAGGGGAAAGAGCCACCCT 
               
               
                 ID 
                 CTCCTGCAGGGCCAGTCAGAGTGTTAGCAGCAGCTACTTAGCCTGGTACCAGCAGAAACCT 
               
               
                 391 
                 GGCCAGGCTCCCAGGCTCCTCATCTATGGTGCATCCAGCAGGGCCACTGGCATCCCAGACA 
               
               
                   
                 GGTTCAGTGGCAGTGGGTCTGGGACAGACTTCACTCTCACCATCAGCAGACTGGAGCCTGA 
               
               
                   
                 AGATTTTGCAGTGTATTACTGTCAGCAGTATAATAACTGGCCTCTCACTTTCGGCGGAGGGA 
               
               
                   
                 CCAAGCTGGAGATCAAACGT 
               
               
                   
               
               
                 SEQ 
                 GACATCCAGTTGACCCAGTCTCCCGACTCCCTGGCTGTGTCTCTGGGCGAGAGGGCCACCAT 
               
               
                 ID 
                 CAACTGCACGTCCAGCCAGAGTGTTTTATACAGCTCCAACAATAAGAACTACATAGCTTGGT 
               
               
                 392 
                 ACCAGCAGAAACCAGGACAGCCTCCTAAGCTGCTCATTTACTGGGCATCTACCCGGGAATC 
               
               
                   
                 CGGGGTCCCTGACCGATTCAGTGGCAGCGGGTCTGGGACAGATTTCACTCTCACCATCAGC 
               
               
                   
                 AGCCTGCAGGCTGAAGATGTGGCAGTTTATTACTGTCAGCAATATTATTATATTCCTCGGAC 
               
               
                   
                 GTTCGGCCAAGGGACCAAGGTGGAAATCAAACGT 
               
               
                   
               
               
                 SEQ 
                 GATGTTGTGATGACTCAGTCTCCACTCTCCCTGCCCGTCACCCCTGGAGAGCCGGCCTCCAT 
               
               
                 ID 
                 CTCCTGCAGGTCTAGTCAGAGCCTCCTGCATAGTAATGGATACAACTATTTGGATTGGTACC 
               
               
                 393 
                 TGCAGAAGCCAGGGCAGTCTCCACAGCTCCTGATCTATTTGGGTTCTAATCGGGCCCCCGGG 
               
               
                   
                 GTCCCTGACAGGTTCAGTGGCAGTGGATCAGGCACAGATTTTACACTGAAAATCAGCAGAG 
               
               
                   
                 TGGAGGCTGAGGATGTTGGGGTTTATTACTGCATGCAAGCTCTACAAACTCGGACATTCGGC 
               
               
                   
                 CAAGGGACCAAGCTGGAGATCAAACGT 
               
               
                   
               
               
                 SEQ 
                 GAAACGACACTCACGCAGTCTCCAGGCACCCTGTCTTTGTCTCCAGGGGAAAGAGCCACCC 
               
               
                 ID 
                 TCTCCTGCAGGGCCAGTCAGAGTCTTACCAGCAGCTACTTAGCCTGGTACCAGCAGAAACCT 
               
               
                 394 
                 GGCCAGGCTCCCAGACTCCTCATCTATCGTGCATCCAGCAGGGCCACTGGCATCCCAGACC 
               
               
                   
                 GGTTCAGTGGCAGTGGGTCTGGGACAGACTTCACTCTCACCATCAGCAGACTGGAGCCTGA 
               
               
                   
                 AGATTTTGCAGTTTATTACTGTCAGCAGTATGGTAGTTCACCTAACACCTTCGGCCAAGGGA 
               
               
                   
                 CACGACTGGAGATTAAACGT 
               
               
                   
               
               
                 SEQ 
                 GAAATTGTGTTGACACAGTCTCCACTCTCCCTGCCCGTCACCCTTGGACAGCCGGCCTCCAT 
               
               
                 ID 
                 CTCCTGCAGGTCTAGTCAAAGCCTCGTACACAGTAATGGACACACCTACTTGAGTTGGTTTC 
               
               
                 395 
                 AGCAGAGGCCAGGCCAATCTCCAAGGCGCCTCATTTATGAGGTTTCTAACCGGGACTCTGG 
               
               
                   
                 TGTCCCAGACAGATTCAGCGGCAGTGGGTCAGGCACTGATTTCACACTAAGAATCAGCAGG 
               
               
                   
                 GTGGAGGCTGAGGATGTTGGGGTTTATTACTGCTTGCAAGGAACACACTGGCCCCCCCTCAC 
               
               
                   
                 TGTCGGCGGAGGGACCAAAGTGGATATCAAACGT 
               
               
                   
               
               
                 SEQ 
                 GATGTTGTGATGACTCAGTCTCCAGCCACCCTGTCTTTGTCTCCAGGGGAAAGAGCCACCCT 
               
               
                 ID 
                 CTCCTGCAGGGCCAGTCAGAGTGTTGGCAGCGACTTAGCCTGGTACCAGCAGAAACCTGGC 
               
               
                 396 
                 CAGGCTCCCAGGCTCCTCATCTACCGTGCATCCACCAGGGCCGCTGGTATCCCAGCCAGGTT 
               
               
                   
                 CAGTGGCAGTGGGTCTGGGACAGACTTCACTCTCACCATCAGCAGACTGGAGCCTGAAGAT 
               
               
                   
                 TTTGCAGTGTTTTACTGTCAGCAGTATGGTAGATCACCGTACACTTCTGGCCAGGGGACCAA 
               
               
                   
                 GCTGGAGATCAAACGT 
               
               
                   
               
               
                 SEQ 
                 GATATTGTGATGACCCACACTCCAGACTCCCTGGCTGTGTCTCTGGGCGAGAGGGCCACCAT 
               
               
                 ID 
                 CAACTGCAAGTCCAGCCAGAGTGTTTTATACAGCTCCAACAATAAGAACTACTTAGCTTGGT 
               
               
                 397 
                 ACCAGCAGAAACCAGGACAGCCTCCTAAGCTGCTCATTTACTGGGCATCTACCCGGGAATC 
               
               
                   
                 CGGGGTCCCTGACCGATTCAGTGGCAGCGGGTCTGGGACAGATTTCACTCTCACCATCAGC 
               
               
                   
                 AGCCTGCAGGCTGAAGATGTGGCAGTTTATTACTGTCAGCAATATTATAGTACTCCGCTCAC 
               
               
                   
                 TTTCGGCGGAGGGACCAAGGTGGAGATCAAACGT 
               
               
                   
               
               
                 SEQ 
                 GAAATTGTGATGACGCAGTCTCCACTCTCCCTGTCCGTCACCCCTGGAGAGCCGGCCTCCAT 
               
               
                 ID 
                 CTCCTGCAGGTCTAGTCAGAGCCTCCTACATAGTAGTGGATACAACTATTTGGATTGGTACC 
               
               
                 398 
                 TGCAGAAGCCAGGCCAGTCTCCACAGCTCCTGATCTATTTGGGTTCTACTCGGGCCTCCGGG 
               
               
                   
                 GTCCCTGACAGGTTCAGTGGCAGTGGATCAGGCACAGATTTTACACTGAAAATCAGCAGAG 
               
               
                   
                 TGGAGGCTGAGGATGTTGGGGTTTATTATTGCATGCAAGGTCTACAAATTCCGCTCACTTTC 
               
               
                   
                 GGCGGAGGGACCAAAGTGGATATCAAACGT 
               
               
                   
               
               
                 SEQ 
                 GATATTGTGATGACCCACACTCCACTCTCTCTGTCCGTCACCCCTGGACAGCCGGCCTCCAT 
               
               
                 ID 
                 CTCCTGCAAGTCTAGTCAGAGCCTCCTGCATAGTGATGGAAAGACCTATTTGTATTGGTACC 
               
               
                 399 
                 TGCAGAAGCCAGGCCAGCCTCCACAGCTCCTGATCTATGAAGTTTCCAACCGGTTCTCTGGA 
               
               
                   
                 GTGCCAGATAGGTTCAGTGGCAGCGGGTCAGGGACAGATTTCACACTGAAAATCAGCCGGG 
               
               
                   
                 TGGAGGCTGAGGATGTTGGGGTTTATTACTGCATGCAAAGTATACAGCTTCCGTGGACGTTC 
               
               
                   
                 GGCCAAGGGACCAAGGTGGAGATCAAACGT 
               
               
                   
               
               
                 SEQ 
                 GAAACGACACTCACGCAGTCTCCAGCCACCCTGTCTGTGTCTCCAGGGGAAAGAGCCACCC 
               
               
                 ID 
                 TCTCCTGCAGGGCCAGTCAGAGTGTTAGCAGCAACTTAGCCTGGTACCAGCAGAAACCTGG 
               
               
                 400 
                 CCAGGCTCCCAGGCTCCTCATCTATGGTGCATCCACCAGGGCCACTGGCATCCCAGCCAGGT 
               
               
                   
                 TCAGTGGCAGTGGGTCTGGGACAGAGTTCACTCTCACCATCAGCAGCCTGCAGTCTGAAGA 
               
               
                   
                 TTTTGCAGTTTATTACTGTCAGCAGTATAATAACTGGCCTCGGTTCGGCCAAGGGACACGAC 
               
               
                   
                 TGGAGATTAAACGT 
               
               
                   
               
               
                 SEQ 
                 GATGTTGTGATGACTCAGTCTCCTTCCACCCTGTCTGCATCTGTAGGGGACAGAGTCACCAT 
               
               
                 ID 
                 CACTTGCCGGGCCAGTCAGACTATTAATAGTTGGTTGGCCTGGTATCAGCAGAAACCAGGG 
               
               
                 401 
                 AAGGCCCCTAAGCTCCTCATCTCTAGGGCGTCTCGTTTAGAAAGTGGGGTCCCATCAAGGTT 
               
               
                   
                 CAGCGGCAGTGCATCTGGCACAGAATACATTCTCACCATCAACAGCCTGCAGCCTGATGAT 
               
               
                   
                 TTTGCAATGTACTTCTGCCATCAATATAATAGTTATTCTCCCACTTTTGGCCAGGGGACCAA 
               
               
                   
                 GCTGGAGATCAAACGT 
               
               
                   
               
               
                 SEQ 
                 GAAACGACACTCACGCAGTCTCCAGGCACCCTGTCTTTGTCTCCAGGGGAAAGAGCCACCC 
               
               
                 ID 
                 TCTCCTGCAGGGCCAGTCAGAGTGTTAGCAGCAGCTACTTAGCCTGGTACCAGCAGAAACC 
               
               
                 402 
                 TGGCCAGGCTCCCAGGCTCCTCATCTATGGTGCATCCAGCAGGGCCACTGGCATCCCAGCCA 
               
               
                   
                 GGTTCAGTGGCAGTGGGTCTGGGACAGACTTCACTCTCACCATCAGCAGCCTAGAGCCTGA 
               
               
                   
                 AGATTTTGCAGTTTATTACTGTCAGCAGCGTTACAACTGGCCTATCACCTTCGGCCAAGGGA 
               
               
                   
                 CACGACTGGAGATTAAACGT 
               
               
                   
               
               
                 SEQ 
                 GAAATTGTGTTGACGCAGTCTCCAGCCACCCTGTCTTTGTCTCCGGGGGAAACAGCCACCCT 
               
               
                 ID 
                 CTCCTGCAGGGCCAGTCAGACTATTGGTCCCAAGTCCTTCGGCTGGTACCAACAGAGACCTG 
               
               
                 403 
                 GCCAGGCTCCCAGGCTCCTCATCTATGACTCCAACAGGGCCACTGGCATCCCAGCCAGGTTC 
               
               
                   
                 AGTGGCAGTGGGTCTGGGACAGACTTCACTCTCACCATCAGCAGCCTAGAGCCTGAAGATT 
               
               
                   
                 TTGCAGTTTATTACTGTCAGCAGCGTAGCAGGTGGCCTCTCACTTTCGGCCCTGGGACCAAA 
               
               
                   
                 GTGGATATCAAACGT 
               
               
                   
               
               
                 SEQ 
                 GATGTTGTGATGACTCAGTCTCCACTCTCCCTGCCCGTCACCCTTGGACAGCCGGCCTCCAT 
               
               
                 ID 
                 CTCCTGCAGGTCTAGTCAAAGCCTCGTGTACAGTGATGGAAACACCTACTTGTATTGGTTTC 
               
               
                 404 
                 AGCAGAGGGCAGGCCAATCTCCAAGGCGCCTGATTTATAAGGTTTCTAAGCGGGACTCTGG 
               
               
                   
                 GGTCCCAGACAGGTTCAGCGGCAGTGGGTCAGGCACTGATTTCACACTGAAAATCAGCAGG 
               
               
                   
                 GTGGAGGCTGAGGATGTTGGAATTTATTACTGCGTGCAAGGTAGACACTGGCCGTACACTC 
               
               
                   
                 TTGGCCAGGGGACCAAGCTGGAGATCAAACGT 
               
               
                   
               
               
                 SEQ 
                 GAAATTGTGTTGACGCAGTCTCCAGGCACCCTGTCTTTGTCTCCAGGGGAAAGAGCCACCCT 
               
               
                 ID 
                 CTCCTGCAGGGCCAGTCAGAGTGTTAGCAGCAGCTACTTAGCCTGGTACCAGCAGAAACCT 
               
               
                 405 
                 GGCCAGGCTCCCAGGCTCCTCATCTATGATGCATCCAACAGGGCCACTGGCATCCCAGCCA 
               
               
                   
                 GGTTCAGTGGCAGTGGATCTGGGACAGAATTCACTCTCACCATCAGCAGCCTGCAGCCTGA 
               
               
                   
                 TGATTTTGCAACTTATTACTGCCAACAGTATAATAGTTATTCAAGGACGTTCGGCCAGGGGA 
               
               
                   
                 CCAAAGTGGATATCAAACGT 
               
               
                   
               
               
                 SEQ 
                 GATGTTGTGATGACTCAGTCTCCTTCCACCCTGTCTGCATCTGTGGGAGACAGAGTCACCAT 
               
               
                 ID 
                 CACTTGCCGGGCCAGTCAGAGTATTACTACCTGGTTGGCCTGGTCTCAGCAGCAACCAGGG 
               
               
                 406 
                 AAAGCCCCTAAGCTCCTCATCTATAAGGCCTCTAGTTTAACAAGTGGGGTCCCATCAAGGTT 
               
               
                   
                 CAGCGGCAGTGGATCTGGGACAGAGTTCACTCTCACCATCAGCAGCCTGCAGCCTGATGAT 
               
               
                   
                 TTTGCAAGTTATTACTGCCATCATTATAATGGTGCTTCTCGTATGTTCGGCCAAGGGACCAA 
               
               
                   
                 GCTGGAGATCAAACGT 
               
               
                   
               
               
                 SEQ 
                 GAAACGACACTCACGCAGTCTCCAGCCACCCTGTCTTTGTCTCCAGGGGAAAGAGCCACCC 
               
               
                 ID 
                 TCTCCTGCAGGGCCAGTCAGAGTGTTAGCAGCTACTTAGCCTGGTACCAACAGAAACCTGG 
               
               
                 407 
                 CCAGGCTCCCAGGCTCCTCATCTATGATGCATCCAACAGGGCCACTGGCATCCCAGCCAGGT 
               
               
                   
                 TCAGTGGCAGTGGGTCTGGGACAGACTTCACTCTCACCATCAGCAGCCTAGAGCCTGAAGA 
               
               
                   
                 TTTTGCAGTTTATTACTGTCAGCAGCGTAGCAACTGGCCTTTCTTCGGCCAAGGGACACGAC 
               
               
                   
                 TGGAGATTAAACGT 
               
               
                   
               
               
                 SEQ 
                 GAAACGACACTCACGCAGTCTCCAGCCACCCTGACTTTGTCTCCAGGGGAAAGAGTCACCC 
               
               
                 ID 
                 TCTCCTGCAGGGCCAGTCAGAGTATTGGCACTTACGTCGCCTGGTATCAGCAGAAACCTGGC 
               
               
                 408 
                 CAGGCTCCCAGATTCCTCATCTATGATTCATCGAATAGGGCCACTGGCATCCCAGCCAGGTT 
               
               
                   
                 CAGTGGTAGTGGGTCTGGGACAGACTTCACTCTCACGATCAGCAGCCTGGAGCCTGAAGAT 
               
               
                   
                 TTTGCATTTTATTACTGTCAACAGCGTGCCGAGTGGCCTCTCACCTTCGGCCAAGGGACACG 
               
               
                   
                 ACTGGAGATTAAACGT 
               
               
                   
               
               
                 SEQ 
                 GATGTTGTGATGACTCAGTCTCCAGGCACCCTGTCTTTGTCTCCAGGGGAAAGAGCCACTCT 
               
               
                 ID 
                 CTCCTGCAGGGCCAGTCAGAGTGTTAATAGCGGCTACTTAGCCTGGTACCAGCAGAAACCT 
               
               
                 409 
                 GGCCAACCTCCCAGACTCCTCATCTCTGGTGTTTCCACCAGGGCCACTGGCATCCCAGACAG 
               
               
                   
                 GTTCAGTGGCAGTGGGTCTGGGACAGACTTCACTCTCACCATCAGCAGACTGGAGCCTGAA 
               
               
                   
                 GATTTTGCAGTGTATTACTGTCAGGAGTATGGTAACTCAGCTATGTACAATTTTGGCCAGGG 
               
               
                   
                 GACCAAGCTGGAGATCAAACGT 
               
               
                   
               
               
                 SEQ 
                 GAAACGACACTCACGCAGTCTCCAGCCACCCTGTCTGTGTCTCCAGGGGAAAGAGCCACCC 
               
               
                 ID 
                 TCTCCTGCAGGGCCAGTCAGAGTGTTAGCAGCAACTTAGCCTGGTACCAGCAGAAACCTGG 
               
               
                 410 
                 CCAGGCTCCCAGGCTCCTCATCTATGGTGCATCCACCAGGGCCACTGGTATCCCAGCCAGGT 
               
               
                   
                 TCAGTGGCAGTGGGTCTGGGACAGAGTTCACTCTCACCATCAGCAGCCTGCAGTCTGAAGA 
               
               
                   
                 TTTTGCAGTTTATTACTGTCAGCAGTATAATAACTGGCCTCCCTTCACCTTCGGCCAAGGGA 
               
               
                   
                 CACGACTGGAGATTAAACGT 
               
               
                   
               
               
                 SEQ 
                 GATGTTGTGATGACTCAGTCTCCAGGCACCCTGTCTTTGTCTCCAGGGGAAAGAGCCACCCT 
               
               
                 ID 
                 CTCCTGCAGGGCCAGTCAGAGTGTTAGCAGCAGCTACTTAGGCTGGTATCAGCAGAAATCC 
               
               
                 411 
                 GGCCAGGCTCCCAGGCTCCTCATCTATGGTGCATCCAGCAGGGCCACTGACATCCCAGACA 
               
               
                   
                 GGTTCAGTGGCAGTGGGTCTGGGACAGACTTCACTCTCACCATCAGCAAACTGGAGGCAGA 
               
               
                   
                 AGATTCTGCAGTGTATTACTGTCAGCAGTATGGTATCTCACCTCTCGCGTTCGGCCAAGGGA 
               
               
                   
                 CCAAGCTGGAGATCAAACGT 
               
               
                   
               
               
                 SEQ 
                 GAAACGACACTCACGCAGTCTCCAGCCACCCTGTCTGTGTCTCCAGGGGAGAGAGCCACCC 
               
               
                 ID 
                 TCTCCTGCAGGGCCAGTCAGAGTATTAGCAACAACTTAGCCTGGTACCAGCAGAAACCTGG 
               
               
                 412 
                 CCAGGCTCCCAGGCTCCTCATCTATGGTACATCCACCAGGGCCACTGGTATCCCAGCCAGGT 
               
               
                   
                 TCAGTGGCAGTGGGTCTGGGACAGAGTTCACTCTCACCATCAGCAGCCTGCAGTCTGAAGA 
               
               
                   
                 TTTTGCAGTTTATTACTGTCAGCAGTATAATTTCTGGCCTTCGATCACCTTCGGCCAAGGGAC 
               
               
                   
                 ACGACTGGAGATTAAACGT 
               
               
                   
               
               
                 SEQ 
                 GAAACGACACTCACGCAGTCTCCAGGCACCCTGTCTTTGTCTCCAGGGGAAAGAGCCACCC 
               
               
                 ID 
                 TCTCCTGCAGGGCCAGTCAGAGTGTTAGCAGCAGCTCCTTAGCCTGGTACCAGCAGAAACC 
               
               
                 413 
                 TGGCCAGGCTCCCAGGCTCCTCATCTATGGTGCATCCAGCAGGGCCACTGGCATCCCAGAC 
               
               
                   
                 AGGTTCAGTGGCAGTGGGTCTGGGACAGACTTCACTCTCACCATCAGCAGACTGGAGCCTG 
               
               
                   
                 AAGATTTTGCAGTGTATTACTGTCAGCAGTATGGTAGCTCACAGACCTTCGGCCAAGGGAC 
               
               
                   
                 ACGACTGGAGATTAAACGT 
               
               
                   
               
               
                 SEQ 
                 GATGTTGTGATGACTCAGTCTCCACTCTCCCTGCCCGTCTCCCTTGGACAGCCGGCCTCCATC 
               
               
                 ID 
                 TCCTGCAGGTCTAATCAAAGCCTCGTATACAGTGATGGAGGCACCTACTTGAATTGGTTTCA 
               
               
                 414 
                 GCAGAGGGCAGGCCAGTCTCCAAGGCGCCTAGTTTATAAGGTTTCTAACCGGGACTCTGGG 
               
               
                   
                 GTCCCAGACAGATTCAGCGGCAGTGGGTCAGGCACTGATTTCACACTGAGAATCAGCAGGG 
               
               
                   
                 TGGAGGCTGAGGATGTTGGGGTTTATTACTGCATGCAAGGGACACACTGGCCGTACACTTTT 
               
               
                   
                 GGCCAGGGGACCAAGCTGGAGATCAAACGT 
               
               
                   
               
               
                 SEQ 
                 GACATCCAGTTGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCACCGT 
               
               
                 ID 
                 CACTTGCCGGGCAAGTCAGAGCATTAGCAGCTATTTAAATTGGTATCAGCAGAAACCAGGG 
               
               
                 415 
                 AAAGCCCCTCAACTCCTGATCTACGATGCATCCAATTTGGAAACAGGGGTCCCCTCAAGGTT 
               
               
                   
                 CAGTGGAAGTGGATCTGGGACAGATTTTACTTTCACCATCAGCAGCCTGCAGCCTGAAGATT 
               
               
                   
                 TTGCAACATATTACTGTCAGCAGTTTGATAATGTCCCAGTCACTTTCGGCGGAGGGACCAAG 
               
               
                   
                 GTGGAAATCAAACGT 
               
               
                   
               
               
                 SEQ 
                 GAAATTGTGCTGACTCAGTCTCCACTCTCCCTGCCCGTCACCCTTGGACAGCCGGCCTCCAT 
               
               
                 ID 
                 CTCCTGCAGGTCTAGTCAAAGCCTCGTATACAGTGATGGAAACACCTACTTGAATTGGTTTC 
               
               
                 416 
                 AGCAGAGGCCAGGCCAATCTCCAAGGCGCCTAATTTATAAGGTTTCTAACCGGGACTCTGG 
               
               
                   
                 GGTCCCAGACAGATTCAGCGGCAGTGGGTCAGGCACTGATTTCACACTGAAAATCAGCAGG 
               
               
                   
                 GTGGAGGCTGAGGATGTTGGGGTTTATTACTGCATGCAAGGTACACACTGGCCTCGAACGT 
               
               
                   
                 TCGGCCAAGGGACCAAGCTGGAGATCAAACGT 
               
               
                   
               
               
                 SEQ 
                 GATGTTGTGATGACTCAGTCTCCAGCCACCCTGTCTGTGTCTCCAGGGGAAAGAGCCACCCT 
               
               
                 ID 
                 CTCCTGCAGGGCCAGTCAGAGTGTTAGCAGCAACTTAGCCTGGTACCAGCAGAAACCTGGC 
               
               
                 417 
                 CAGGCTCCCAGGCTCCTCATCTATGGTGCATCCAGCAGGGCCACTGGCATCCCAGACAGGTT 
               
               
                   
                 CAGTGGCAGTGGGTCTGGGACAGACTTCACTCTCACCATCAACAGACTGGAGCCTGAAGAT 
               
               
                   
                 TTTGCAGTGTATTACTGTCAGCAGTATGGTAGCTCATCCATGTACACTTTTGGCCAGGGGAC 
               
               
                   
                 CAAGCTGGAGATCAAACGT 
               
               
                   
               
               
                 SEQ 
                 GATGTTGTGATGACTCAGTCTCCATCCTCCCTGTCTGCATCTGTGGGGGACAGCGTCGCCAT 
               
               
                 ID 
                 CACTTGCCGGGCAAGTCAGAGCATTAGCAACTATTTAAATTGGTATCAGCAGAGACCAGGG 
               
               
                 418 
                 AAAGCCCCTAAGCTCCTGATCTTTGCTGCATCCAGTTTGCAAAGTGGGGTCCCATCAAGGTT 
               
               
                   
                 CAGTGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGTCTGCAACCTGAAGATT 
               
               
                   
                 TTGCAACTTACTCCTGTCAACAGAGTTACATTACCCCGTGGACGTTCGGCCAAGGGACCAAG 
               
               
                   
                 CTGGAGATCAAACGT 
               
               
                   
               
               
                 SEQ 
                 GATGTTGTGATGACTCAGTCTCCAGGCACCCTGTCTTTGTCTCCAGGGGAAAGAGCCACCCT 
               
               
                 ID 
                 CTCCTGCAGGGCCAGTCAGAGTGTTAGCACCCTCTTAGCCTGGTACCAACAGAAACCTGGC 
               
               
                 419 
                 CAGGCTCCCAGGCTCCTCATCTATGATGCATCCAACAGGGCCACTGGCATCCCAGGCAGGTT 
               
               
                   
                 CAGTGCCAGTGGGTCTGGGACAGACTTCAGTCTCACCATCAGCAGCCTAGAGACTGAAGAT 
               
               
                   
                 TCTGCAGTTTATTACTGTCAGCACCGTTACGTGTGGCCGTTCACTTTCGGCGGAGGGACCAA 
               
               
                   
                 GCTGGAGATCAAACGT 
               
               
                   
               
               
                 SEQ 
                 GACATCCAGATGACCCAGTCTCCATCCTCCCTGTCTGCATCTGTAGGAGACAGAGTCACCAT 
               
               
                 ID 
                 CACTTGCCGGGCAAGTCAGGGCATTAGAAATGATTTAGGCTGGTATCAGCAGAAACCAGGG 
               
               
                 420 
                 AAAGCCCCTAAGCGTCTGATCTATGGTGCATCCAGTTTGCAAAGTGGAGTCCCATCAAGGTT 
               
               
                   
                 CAGCGGCAGTGGATCTGGGACAGAATTCACTCTCACAATCAGGAGCCTGCAGCCTGAAGAT 
               
               
                   
                 TTTGCAACTTATTATTGTCTACAGCATAATTCCTACCCTCGAACATTCGGCCAAGGGACCAA 
               
               
                   
                 GGTGGAAATCAAACGT 
               
               
                   
               
               
                 SEQ 
                 GATGTTGTGATGACTCAGTCTCCAGCCACCCTGTCTTTGTCTCCAGGGGAAAGAGCCACCCT 
               
               
                 ID 
                 CTCCTGCAGGGCCAGTCAGAGTGTTAGCAGCTACTTAGCCTGGTACCAACAGAAACCTGGC 
               
               
                 421 
                 CAGGCTCCCAGGCTCCTCATCTATGATGCATCCAACAGGGCCACTGGCATCCCAGCCAGGTT 
               
               
                   
                 CAGTGGCAGTGGGTCTGGGACAGACTTCACTCTCACCATCAGCAGCCTAGAGCCTGAAGAT 
               
               
                   
                 TTTGCAGTTTATTACTGTCAGCAGCGTAGCAACTGGCCGTGGACGTTCGGCCAAGGGACCA 
               
               
                   
                 AGCTGGAGATCAAACGT 
               
               
                   
               
               
                 SEQ 
                 GATGTTGTGATGACTCAGTCTCCGCTCTCCCTGCCCGTCACCCTTGGACAGGCGGCCTCCAT 
               
               
                 ID 
                 CTCCTGCAGGTCTAGTCATAGCCTCACAACTACTGATGGACGTACTTACGTGGCTTGGTTTC 
               
               
                 422 
                 AGCAGAGGCCAGGCCAATCTCCAAGGCGCCTTCTTTATGAGGTTTCTAAGCGGGACTCTGG 
               
               
                   
                 GGCCCCAGACAGATTCAGCGGCAGTGGGTCAGGCACTGATTTCACTCTGAAAATCAGCAGG 
               
               
                   
                 GTGGAGGCTGACGATGTTGGAATTTATCATTGCATGCAAGGAACACATGGGCCTCACACGT 
               
               
                   
                 TCGGCCAAGGGACCAAGCTGGAGATCAAACGT 
               
               
                   
               
               
                 SEQ 
                 GAAACGACACTCACGCAGTCTCCAGCCACCCTGTCTGTGTCTCCAGGGGAAAGAGCCACCC 
               
               
                 ID 
                 TCTCCTGCAGGGCCAGTCAAAGTGTTACCAGCAACTTAGCCTGGTACCAGCAGAAACCTGG 
               
               
                 423 
                 CCAGGCTCCCAGGCTCCTCATCTATGGTGCATCCAACAGGGCCACTGGTATCCCAGCCAGGT 
               
               
                   
                 TCAGTGTCAGTGGGTCTGGGACAGACTTCACTCTCACCATCAGCAGACTGGAGCCTGAAGA 
               
               
                   
                 TTTTGCAGTGTATTACTGTCAGCAGTATGGTAGTCCACCTCCGACCACCTTCGGCCAAGGGA 
               
               
                   
                 CACGACTGGAGATTAAACGT 
               
               
                   
               
               
                 SEQ 
                 GATGTTGTGATGACTCAGTCTCCAGGCACCCTGTCTTTGTCTCCAGGGGAAAGAGCCACCCT 
               
               
                 ID 
                 CTCCTGCAGGGCCAGTCAGAGTGTTAGCAGCAGCTACTTAGCCTGGTACCAGCAGAAACCT 
               
               
                 424 
                 GGCCAGGCTCCCAGGCTCCTCATCTATGGTGCATCCAGCAGGGCCACTGGCATCCCAGACA 
               
               
                   
                 GGTTCAGTGGCAGTGGGTCTGGGACAGACTTCACTCTCACCATCAGCAGACTGGAGCCTGA 
               
               
                   
                 AGATTTTGCAGTGTATTACTGTCAGCAGTATGGTAGCTCACGTCGGACGTTCGGCCAAGGGA 
               
               
                   
                 CCAAGCTGGAGATCAAACGT 
               
               
                   
               
               
                 SEQ 
                 GAAACGACACTCACGCAGTCTCCAGGCACCCTGTCCTTGTCTCCAGGGGAAAGAGCCACCC 
               
               
                 ID 
                 TCTCCTGCAGGGCCAGTCAGAGTGTTTTCAACAACTACTTAGCCTGGTACCAACAGAGACCT 
               
               
                 425 
                 GGCCAGGCTCCCAGGCTCCTCATCTATGGTGCATCCAGCAGGGCCACTGGCATCCCAGACA 
               
               
                   
                 GGTTCAGTGGCGGTGGGTCTGGGACAGACTTCACTCTCACCATCAGCAGACTGGAGCCTGA 
               
               
                   
                 AGATTTCGCAGTGTATTGCTGTCAGCAGTATGGTAGTTCACCGATCACCTTCGGCCAAGGGA 
               
               
                   
                 CACGACTGGAGATTAAACGT 
               
               
                   
               
               
                 SEQ 
                 GAAATTGTGCTGACTCAGTCTCCAGCCACCCTGTCTTTGTCTCCAGGGGAAAGAGCCACCCT 
               
               
                 ID 
                 CTCCTGCAGGGCCAGTCAGAGTGTTAGCAGCTACTTAGCCTGGTACCAACAGAAACCTGGC 
               
               
                 426 
                 CAGGCTCCCAGGCTCCTCATCTATGATGCATCCAACAGGGCCACTGGCATCCCAGCCAGGTT 
               
               
                   
                 CAGTGGCAGTGGGTCTGGGACAGACTTCACTCTCACCATCAGCAGACTGGAGCCTGAAGAT 
               
               
                   
                 TTTGCAGTGTATTACTGTCAGCAGTATGGTAGCTCACTCAGGTACACTTTTGGCCAGGGGAC 
               
               
                   
                 CAAGCTGGAGATCAAACGT 
               
               
                   
               
               
                 SEQ 
                 GAAATTGTGCTGACTCAGTCTCCAGACTCCCTGGCTGTGTCTCTGGGCGAGAGGGCCACCAT 
               
               
                 ID 
                 CAACTGCAAGTCCAGCCAGAGTGTTTTATATGATTCCAACAGTAAGAACTACTTAAGTTGGT 
               
               
                 427 
                 ATCAGCAGAAACCAGGCCAGCCTCCTAAGTTGCTCATTTCCTGGGCGTCTACCCGGGGGTCC 
               
               
                   
                 GGGGTCCCTGACCGATTCAGTGGCAGCGGGTCTGGGACAGATTTCACTCTCACCATCAGCA 
               
               
                   
                 GCCTGCAGGCTGAAGATGTGGCAGTTTATTACTGTCAGCAATTTTATGGTATTCCCCACTTC 
               
               
                   
                 GGCCAAGGGACACGACTGGAGATTAAACGT 
               
               
                   
               
               
                 SEQ 
                 GATGTTGTGATGACTCAGTCTCCAGCCACCCTGTCTTTGTCTCCAGGGGAAAGAGCCACCCT 
               
               
                 ID 
                 CTCCTGCAGGGCCAGTCAGAGTGTTGGTACCAATTTAGCCTGGTACCAGCAGAAACCTGGC 
               
               
                 428 
                 CAGGCTCCCAGGCTCCTCATCTATGATGCATCCAACAGGGCCACTGGCATCCCAGCCAGGTT 
               
               
                   
                 CAGTGGCAGTGGGTCTGGGACAGAGTTCACTCTCACCATCAGCAGCCTGCAGTCTGAAGAT 
               
               
                   
                 TTTGCAGTTTATTACTGTCAGCAGTATAATAACTGGCCTCCGATAACTTTCGGCGGAGGGAC 
               
               
                   
                 CAAGCTGGAGATCAAACGT 
               
               
                   
               
               
                 SEQ 
                 GATGTTGTGATGACTCAGTCTCCACTCTCCCTGCCCGTCACCCTTGGACAGCCGGCCTCCAT 
               
               
                 ID 
                 CTCCTGCAGGTCTAGTCAAAGCCTCGTATACAGTGATGGAAACACCTACTTGAGTTGGCTTC 
               
               
                 429 
                 AGCAGAGGCCAGGCCAGCCTCCAAGACTCCTAATTTATAAGATTTCTAACCGGTTCTCTGGG 
               
               
                   
                 GTCCCAGACAGATTCAGTGGCAGTGGGGCAGGGACAGATTTCACACTGAAAATCAGCAGGG 
               
               
                   
                 TGGAAGCTGAGGATGTCGGGGTTTATTACTGCATGCAAGGTACACAATTTCCTCAAACGTTC 
               
               
                   
                 GGCCAAGGGACCAAGCTGGAGATCAAACGT 
               
               
                   
               
               
                 SEQ 
                 GAAATTGTGCTGACTCAGTCTCCAGGCACCCTGTCTTTGTCTCCAGGGGAAAGAGCCACCCT 
               
               
                 ID 
                 CTCCTGCAGGGCCAGTCAGAGTGTAATAAGCAGGTACTTAGCCTGGTATCAGCAGAAACCT 
               
               
                 430 
                 GGCCAGGCTCCCAGGCTCCTCATCCATGGTGCATCCACCAGGGCCACTGGCATCCCAGACA 
               
               
                   
                 GGTTCAGTGGCAGTGGGTCTGGGACAGACTTCACTCTCACCATCAGCAGACTGGAGCCTGA 
               
               
                   
                 AGACTTTGCAGTGTATTACTGTCAGCAGTATGGTAGCTCACCTCCGTACACTTTTGGCCAGG 
               
               
                   
                 GGACCAAGGTGGAAATCAAACGT 
               
               
                   
               
               
                 SEQ 
                 GACATCCAGTTGACCCAGTCTCCTTCCACCCTGGCTGCATCTGTAGGAGACAGAGTCACCAT 
               
               
                 ID 
                 CACTTGCCGGGCCAGTCAGAGTATTAGTAGCTGGTTGGCCTGGTATCAGCAGAAACCAGGG 
               
               
                 431 
                 AAAGCCCCTAAGGTCCTGATCTATAAGGCGTCTAGTTTAGAAAGTGGGGTCCCATCAAGGT 
               
               
                   
                 TCAGCGGCAGTGGATCTGGGACAGAATTCACTCTCACCATCAGCAGCCTGCAGCCTGATGA 
               
               
                   
                 TTTTGCAACTTATTACTGCCAACAGTATAATAGTTATTCGGGGACGTTCGGCCAAGGGACCA 
               
               
                   
                 AGGTGGAAATCAAACGT 
               
               
                   
               
               
                 SEQ 
                 GATGTTGTGATGACTCAGTCTCCAGCCATCCTGTCTGTGTCTCCAGGGGAAAGAGCCACCCT 
               
               
                 ID 
                 CTCCTGCAGGGCCAGTCAGAGTGTTAGTAGCAGCTTAGCCTGGTACCAGCAGAAACCTGGC 
               
               
                 432 
                 CAGCCTCCCAGGCTCCTCATCTATGGTGCCTCCACCAGGGCCACTGCTATCCCAGCCAGGTT 
               
               
                   
                 CAGTGGCAGTGGGTCTGGGACAGAGTTCACTCTCACCATCAGCAGCCTGCAGTCTGAAGAT 
               
               
                   
                 TTTGCAGTTTATTACTGTCAGCGCTATGATAACTGGCCTCCCCTTTTTGGCCAGGGGACCAA 
               
               
                   
                 GCTGGAGATCAAACGT 
               
               
                   
               
            
           
         
       
     
     Exemplary CDR amino acid sequences of CLEC2D antibodies of the disclosure are shown in Table 6 below. 
     
       
         
           
               
             
               
                 TABLE 6 
               
             
            
               
                   
               
               
                 CDR Amino Acid Sequences 
               
            
           
           
               
               
            
               
                 VH 
                 VL 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
               
            
               
                 SEQ 
                   
                 SEQ 
                   
                 SEQ 
                   
                 SEQ 
                   
                 SEQ 
                   
                 SEQ 
                   
               
               
                 ID 
                 CDRH1 
                 ID 
                 CDRH2 
                 ID 
                 CDRH3 
                 ID 
                 CDRL1 
                 ID 
                 CDRL2 
                 ID 
                 CDRL3 
               
               
                   
               
               
                 SEQ 
                 GYTFT 
                 SEQ  
                 WINAGNG 
                 SEQ 
                 GSLSRSGWY 
                 SEQ 
                 ASQSIGS 
                 SEQ 
                 SAT 
                 SEQ 
                 YGSS 
               
               
                 ID 
                 SYAM 
                 ID 
                 NTKYSQKF 
                 ID 
                 AGLFDY 
                 ID 
                 NLVW 
                 ID 
                 SRA 
                 ID 
                 PPTT 
               
               
                 433 
                 H 
                 486 
                 QG 
                 547 
                   
                 654 
                   
                 727 
                 TG 
                 784 
                 F 
               
               
                   
               
               
                 SEQ 
                 GFTFS 
                 SEQ 
                 IISDDGSKS 
                 SEQ 
                 DRGTKWNQ 
                 SEQ 
                 ASQSVSS 
                 SEQ 
                 GAS 
                 SEQ 
                 YGSS 
               
               
                 ID 
                 SYSMN 
                 ID 
                 YYADSVQ 
                 ID 
                 LNDVFDM 
                 ID 
                 SYLAW 
                 ID 
                 NRA 
                 ID 
                 PGTF 
               
               
                 434 
                   
                 487 
                 G 
                 548 
                   
                 655 
                   
                 728 
                 TG 
                 785 
                   
               
               
                   
               
               
                 SEQ 
                 GYTFT 
                 SEQ 
                 IINPSGGST 
                 SEQ 
                 GRGYSSSRL 
                 SEQ 
                 ASQSVSS 
                 SEQ 
                 DAS 
                 SEQ 
                 RSN 
               
               
                 ID 
                 SYYM 
                 ID 
                 SYAQKFQ 
                 ID 
                 YYFDY 
                 ID 
                 YLAW 
                 ID 
                 NRA 
                 ID 
                 WPRT 
               
               
                 435 
                 H 
                 488 
                 G 
                 549 
                   
                 656 
                   
                 729 
                 TG 
                 786 
                 F 
               
               
                   
               
               
                 SEQ 
                 GFTFS 
                 SEQ 
                 RITNKRTG 
                 SEQ 
                 DVSGSFAAY 
                 SEQ 
                 SSRNILYS 
                 SEQ 
                 WAS 
                 SEQ 
                 SSSLP 
               
               
                 ID 
                 DPYM 
                 ID 
                 YATTYAA 
                 ID 
                   
                 ID 
                 GNNKNFL 
                 ID 
                 TRE 
                 ID 
                 HTF 
               
               
                 436 
                 D 
                 489 
                 SVKD 
                 550 
                   
                 657 
                 AW 
                 730 
                 SG 
                 787 
                   
               
               
                   
               
               
                 SEQ 
                 GFTFS 
                 SEQ 
                 WINAGNG 
                 SEQ 
                 EGGAVAGTV 
                 SEQ 
                 ASESVSK 
                 SEQ 
                 GAS 
                 SEQ 
                 YGSS 
               
               
                 ID 
                 SYAM 
                 ID 
                 NTKYSQKF 
                 ID 
                 Y 
                 ID 
                 SYLLW 
                 ID 
                 TRA 
                 ID 
                 RTF 
               
               
                 437 
                 H 
                 490 
                 QG 
                 551 
                   
                 658 
                   
                 731 
                 SG 
                 788 
                   
               
               
                   
               
               
                 SEQ 
                 GFTFS 
                 SEQ 
                 RIKSKTDG 
                 SEQ 
                 DEYFY 
                 SEQ 
                 ASQSISST 
                 SEQ 
                 GAS 
                 SEQ 
                 YGNS 
               
               
                 ID 
                 NAWM 
                 ID 
                 GTTDYAA 
                 ID 
                   
                 ID 
                 YLAW 
                 ID 
                 TRA 
                 ID 
                 PPGA 
               
               
                 438 
                 S 
                 491 
                 PVKG 
                 552 
                   
                 659 
                   
                 732 
                 TG 
                 789 
                 TF 
               
               
                   
               
               
                 SEQ 
                 GGSFS 
                 SEQ 
                 EINHSGST 
                 SEQ 
                 VNPGSYTRE 
                 SEQ 
                 SSQALRN 
                 SEQ 
                 STS 
                 SEQ 
                 HHDF 
               
               
                 ID 
                 GYYW 
                 ID 
                 NYNPSLKS 
                 ID  
                 VSNFDY 
                 ID 
                 VVGLGD 
                 ID 
                 TLQ 
                 ID 
                 PFTF 
               
               
                 439 
                 S 
                 492 
                   
                 553 
                   
                 660 
                 DLAW 
                 733 
                 SG 
                 790 
                   
               
               
                   
               
               
                 SEQ 
                 GDSVS 
                 SEQ 
                 RTYYRSQ 
                 SEQ 
                 RGHNYGVD 
                 SEQ 
                 SSQSLLN 
                 SEQ 
                 LGS 
                 SEQ 
                 SLQT 
               
               
                 ID 
                 SNSVT 
                 ID 
                 WYYNYAV 
                 ID 
                 Y 
                 ID 
                 SNGYNYL 
                 ID 
                 NRA 
                 ID 
                 PLTF 
               
               
                 440 
                 WN 
                 493 
                 SVKS 
                 554 
                   
                 661 
                 EW 
                 734 
                 SG 
                 791 
                   
               
               
                   
               
               
                 SEQ 
                 GYTFA 
                 SEQ 
                 RIKSKTDG 
                 SEQ 
                 GVGWSPFQY 
                 SEQ 
                 ASQSVSS 
                 SEQ 
                 GAS 
                 SEQ 
                 YGSS 
               
               
                 ID 
                 AYYL 
                 ID 
                 ETTDYAAP 
                 ID 
                   
                 ID 
                 NLAW 
                 ID 
                 SRA 
                 ID 
                 PRITF 
               
               
                 441 
                 H 
                 494 
                 VKG 
                 555 
                   
                 662 
                   
                 735 
                 TG 
                 792 
                   
               
               
                   
               
               
                 SEQ 
                 GFTFS 
                 SEQ 
                 FIRSKAYG 
                 SEQ 
                 DDKIAAAGF 
                 SEQ 
                 ASQSVRD 
                 SEQ 
                 AAS 
                 SEQ 
                 YNN 
               
               
                 ID 
                 SHLM 
                 ID 
                 GTTEYAAS 
                 ID 
                 TYWYFDL 
                 ID 
                 NVGW 
                 ID 
                 SM 
                 ID 
                 WPP 
               
               
                 442 
                 H 
                 495 
                 VKG 
                 556 
                   
                 663 
                   
                 736 
                 TG 
                 793 
                 MYTF 
               
               
                   
               
               
                 SEQ 
                 GGSISS 
                 SEQ 
                 RISPGNGV 
                 SEQ 
                 EAADDPFDH 
                 SEQ 
                 ASQSISSY 
                 SEQ 
                 DVS 
                 SEQ 
                 FNN 
               
               
                 ID 
                 GGYS 
                 ID 
                 TSYAQKFQ 
                 ID 
                   
                 ID 
                 LNW 
                 ID 
                 TRA 
                 ID 
                 WPYT 
               
               
                 443 
                 WS 
                 496 
                 G 
                 557 
                   
                 664 
                   
                 737 
                 TD 
                 794 
                 F 
               
               
                   
               
               
                 SEQ 
                 GDSVS 
                 SEQ 
                 VISYDGTS 
                 SEQ 
                 ADYKYD 
                 SEQ 
                 ASQSVNS 
                 SEQ 
                 DAS 
                 SEQ 
                 SYSIP 
               
               
                 ID 
                 NNRA 
                 ID 
                 KYYGDSV 
                 ID 
                   
                 ID 
                 NVAW 
                 ID 
                 SRA 
                 ID 
                 RTF 
               
               
                 444 
                 AWN 
                 497 
                 KG 
                 558 
                   
                 665 
                   
                 738 
                 TG 
                 795 
                   
               
               
                   
               
               
                 SEQ 
                 GYTFT 
                 SEQ 
                 YIYHSGST 
                 SEQ 
                 HRRPIYDILT 
                 SEQ 
                 ASQSVSS 
                 SEQ 
                 DSS 
                 SEQ 
                 CASS 
               
               
                 ID 
                 SYGIS 
                 ID 
                 YYNPSLKS 
                 ID 
                 GFDY 
                 ID 
                 SALAW 
                 ID 
                 SRA 
                 ID 
                 PPVT 
               
               
                 445 
                   
                 498 
                   
                 559 
                   
                 666 
                   
                 739 
                 TG 
                 796 
                 F 
               
               
                   
               
               
                 SEQ 
                 GYSFT 
                 SEQ 
                 YISSSGSYT 
                 SEQ 
                 EDTMVRGVI 
                 SEQ 
                 SSQSLLH 
                 SEQ 
                 MGS 
                 SEQ 
                 YGSS 
               
               
                 ID 
                 SWIG 
                 ID 
                 NYADSVK 
                 ID 
                 P 
                 ID 
                 SNGYNYL 
                 ID 
                 SRA 
                 ID 
                 PRVT 
               
               
                 446 
                   
                 499 
                 G 
                 560 
                   
                 667 
                 DW 
                 740 
                 SG 
                 797 
                 F 
               
               
                   
               
               
                 SEQ 
                 GYSFT 
                 SEQ 
                 WISAYNG 
                 SEQ 
                 DRRYYDSSG 
                 SEQ 
                 ASQGISSS 
                 SEQ 
                 AAS 
                 SEQ 
                 FNTY 
               
               
                 ID 
                 SYWIA 
                 ID 
                 NTNYAQK 
                 ID 
                 YYPAYYFDY 
                 ID 
                 LAW 
                 ID 
                 TLQ 
                 ID 
                 PNTF 
               
               
                 447 
                   
                 500 
                 LQG 
                 561 
                   
                 668 
                   
                 741 
                   
                 798 
                   
               
               
                   
               
               
                 SEQ 
                 GFTFT 
                 SEQ 
                 IIYPGDSDT 
                 SEQ 
                 DGGYDSSGF 
                 SEQ 
                 SCQSLVY 
                 SEQ 
                 KVS 
                 SEQ 
                 TLHT 
               
               
                 ID 
                 DAWM 
                 ID 
                 RYSPSFQG 
                 ID 
                 HFDY 
                 ID 
                 SDGNTYL 
                 ID 
                 NRD 
                 ID 
                 VTF 
               
               
                 448 
                 N 
                 501 
                   
                 562 
                   
                 669 
                 NC 
                 742 
                 SG 
                 799 
                   
               
               
                   
               
               
                 SEQ 
                 GFTFS 
                 SEQ 
                 WIIPIFGIA 
                 SEQ 
                 LPSSGYLQD 
                 SEQ 
                 ASEGLTT 
                 SEQ 
                 LGS 
                 SEQ 
                 YGSS 
               
               
                 ID 
                 NNWM 
                 ID 
                 NYAQKFQ 
                 ID 
                 HHYYGMDV 
                 ID 
                 NLAW 
                 ID 
                 TRA 
                 ID 
                 LLF 
               
               
                 449 
                 T 
                 502 
                 G 
                 563 
                   
                 670 
                   
                 743 
                 SG 
                 800 
                   
               
               
                   
               
               
                 SEQ 
                 GFTFS 
                 SEQ 
                 VIYPGDSD 
                 SEQ 
                 AAVGDGYSY 
                 SEQ 
                 SSQSLEH 
                 SEQ 
                 AAS 
                 SEQ 
                 YDNL 
               
               
                 ID 
                 SYGM 
                 ID 
                 TRYSPSFQ 
                 ID 
                 GRLD 
                 ID 
                 TDGNTYL 
                 ID 
                 TRA 
                 ID 
                 PPLT 
               
               
                 450 
                 H 
                 503 
                 G 
                 564 
                   
                 671 
                 SW 
                 744 
                 TG 
                 801 
                 F 
               
               
                   
               
               
                 SEQ 
                 GFTFD 
                 SEQ 
                 RVKNKAD 
                 SEQ 
                 LPSYYYDSS 
                 SEQ 
                 ASQSISGS 
                 SEQ 
                 KVS 
                 SEQ 
                 ALQT 
               
               
                 ID 
                 DYAM 
                 ID 
                 GETTDYA 
                 ID 
                 GYFTWYFDL 
                 ID 
                 YLAW 
                 ID 
                 TRF 
                 ID 
                 PYTF 
               
               
                 451 
                 H 
                 504 
                 APVKG 
                 565 
                   
                 672 
                   
                 745 
                 SG 
                 802 
                   
               
               
                   
               
               
                 SEQ 
                 GFTFS 
                 SEQ 
                 NIKQDGTE 
                 SEQ 
                 ELYNYGSKD 
                 SEQ 
                 SSQSLLH 
                 SEQ 
                 DAS 
                 SEQ 
                 GLQT 
               
               
                 ID 
                 NYVM 
                 ID 
                 KHYVDSV 
                 ID 
                 YFDY 
                 ID 
                 SNGNNYL 
                 ID 
                 SRA 
                 ID 
                 PFTF 
               
               
                 452 
                 S 
                 505 
                 KG 
                 566 
                   
                 673 
                 DW 
                 746 
                 FG 
                 803 
                   
               
               
                   
               
               
                 SEQ 
                 GFTFS 
                 SEQ 
                 VISYDGSN 
                 SEQ 
                 GGTWDTAM 
                 SEQ 
                 ASQNIRH 
                 SEQ 
                 AAS 
                 SEQ 
                 YGSS 
               
               
                 ID 
                 SYAMS 
                 ID 
                 KYYADSV 
                 ID 
                 VTGFDY 
                 ID 
                 WLVW 
                 ID 
                 NLQ 
                 ID 
                 PALT 
               
               
                 453 
                   
                 506 
                 KG 
                 567 
                   
                 674 
                   
                 747 
                 SG 
                 804 
                 F 
               
               
                   
               
               
                 SEQ 
                 GYTFT 
                 SEQ 
                 AISGSGGS 
                 SEQ 
                 PHYDILTGSR 
                 SEQ 
                 ASQSIGG 
                 SEQ 
                 YAS 
                 SEQ 
                 ALHT 
               
               
                 ID 
                 SYDIN 
                 ID 
                 TYYADSV 
                 ID 
                 APFDY 
                 ID 
                 SLHW 
                 ID 
                 QSF 
                 ID 
                 PWTF 
               
               
                 454 
                   
                 507 
                 KG 
                 568 
                   
                 675 
                   
                 748 
                 SG 
                 805 
                   
               
               
                   
               
               
                 SEQ 
                 GYTFT 
                 SEQ 
                 YISSTSSTI 
                 SEQ 
                 ARVESKDGY 
                 SEQ 
                 ASQSVTS 
                 SEQ 
                 GAS 
                 SEQ 
                 YNH 
               
               
                 ID 
                 DYAIH 
                 ID 
                 YYADSVK 
                 ID 
                 FDY 
                 ID 
                 NYLAW 
                 ID 
                 YRA 
                 ID 
                 WNY 
               
               
                 455 
                   
                 508 
                 G 
                 569 
                   
                 676 
                   
                 749 
                 TG 
                 806 
                 TF 
               
               
                   
               
               
                 SEQ 
                 GFTVS 
                 SEQ 
                 AISGIGDTT 
                 SEQ 
                 DLRLSTWDA 
                 SEQ 
                 ASQSISSN 
                 SEQ 
                 WAS 
                 SEQ 
                 GSN 
               
               
                 ID 
                 SNYMS 
                 ID 
                 YYADSVK 
                 ID 
                 YDF 
                 ID 
                 LAW 
                 ID 
                 ARE 
                 ID 
                 WPLT 
               
               
                 456 
                   
                 509 
                 G 
                 570 
                   
                 677 
                   
                 750 
                 SG 
                 807 
                 F 
               
               
                   
               
               
                 SEQ 
                 GGTFS 
                 SEQ 
                 WMNPNSG 
                 SEQ 
                 NSQRSFDY 
                 SEQ 
                 SSQSVLY 
                 SEQ 
                 TAS 
                 SEQ 
                 ATHY 
               
               
                 ID 
                 SYAIS 
                 ID 
                 NTGYAQK 
                 ID 
                   
                 ID 
                 SSNNKNY 
                 ID 
                 KRA 
                 ID 
                 PRTF 
               
               
                 457 
                   
                 510 
                 FQG 
                 571 
                   
                 678 
                 LAW 
                 751 
                 TG 
                 808 
                   
               
               
                   
               
               
                 SEQ 
                 GFTFS 
                 SEQ 
                 WINAGDG 
                 SEQ 
                 DLGDPRGGIL 
                 SEQ 
                 ASQSLST 
                 SEQ 
                 ASS 
                 SEQ 
                 YGSS 
               
               
                 ID 
                 SYAIS 
                 ID 
                 GTKSSREF 
                 ID 
                 NY 
                 ID 
                 NLAW 
                 ID 
                 TLQ 
                 ID 
                 PIFTF 
               
               
                 458 
                   
                 511 
                 QG 
                 572 
                   
                 679 
                   
                 752 
                 SG 
                 809 
                   
               
               
                   
               
               
                 SEQ 
                 GFTFS 
                 SEQ 
                 VIYSGGST 
                 SEQ 
                 SSPWGELSL 
                 SEQ 
                 ASQSISS 
                 SEQ 
                 WAS 
                 SEQ 
                 GLQI 
               
               
                 ID 
                 SYAIH 
                 ID 
                 YYADSVK 
                 ID 
                 YQGAFDI 
                 ID 
                 WLAW 
                 ID 
                 TRD 
                 ID 
                 PITF 
               
               
                 459 
                   
                 512 
                 G 
                 573 
                   
                 680 
                   
                 753 
                 SG 
                 810 
                   
               
               
                   
               
               
                 SEQ 
                 GYTFT 
                 SEQ 
                 GIIPIFGTA 
                 SEQ 
                 DNDFWSGKV 
                 SEQ 
                 ASHSVGA 
                 SEQ 
                 DAS 
                 SEQ 
                 HNSY 
               
               
                 ID 
                 SSDIN 
                 ID 
                 NYAQKFQ 
                 ID 
                 FDY 
                 ID 
                 NYIAW 
                 ID 
                 TRA 
                 ID 
                 PWTF 
               
               
                 460 
                   
                 513 
                 G 
                 574 
                   
                 681 
                   
                 754 
                 TG 
                 811 
                   
               
               
                   
               
               
                 SEQ 
                 GDSVS 
                 SEQ 
                 GIIPMYGT 
                 SEQ 
                 EGGSGWRHY 
                 SEQ 
                 ASQGIAN 
                 SEQ 
                 GAS 
                 SEQ 
                 SISLP 
               
               
                 ID 
                 SNSAA 
                 ID 
                 ANYAQKF 
                 ID 
                 FDY 
                 ID 
                 YLAW 
                 ID 
                 SLQ 
                 ID 
                 LTF 
               
               
                 461 
                 WN 
                 514 
                 QG 
                 575 
                   
                 682 
                   
                 755 
                 SG 
                 812 
                   
               
               
                   
               
               
                 SEQ 
                 GDSVS 
                 SEQ 
                 WMNPNSG 
                 SEQ 
                 DYCSSTSCQ 
                 SEQ 
                 SSQSVLY 
                 SEQ 
                 KAS 
                 SEQ 
                 YASS 
               
               
                 ID 
                 SNNAA 
                 ID 
                 NTGYAEK 
                 ID 
                 NWFDP 
                 ID 
                 RTNNKN 
                 ID 
                 TLA 
                 ID 
                 VTF 
               
               
                 462 
                 WN 
                 515 
                 FQG 
                 576 
                   
                 683 
                 YLAW 
                 756 
                 NG 
                 813 
                   
               
               
                   
               
               
                 SEQ 
                 GFSLS 
                 SEQ 
                 RTYYRSK 
                 SEQ 
                 GRVAGDAFD 
                 SEQ 
                 SNRSVLY 
                 SEQ 
                 GAS 
                 SEQ 
                 YNN  
               
               
                 ID 
                 TSGVG 
                 ID 
                 WYNDYAV 
                 ID 
                 I 
                 ID 
                 SPNNQNY 
                 ID 
                 SRA 
                 ID 
                 WPRT 
               
               
                 463 
                 VG 
                 516 
                 SVKS 
                 577 
                   
                 684 
                 LGW 
                 757 
                 AG 
                 814 
                 F 
               
               
                   
               
               
                 SEQ 
                 GGSISS 
                 SEQ 
                 RTFYRSK 
                 SEQ 
                 DQGAAAGTL 
                 SEQ 
                 ASESVNS 
                 SEQ 
                 KVS 
                 SEQ 
                 FYSP 
               
               
                 ID 
                 YYWS 
                 ID 
                 WYNDYAV 
                 ID 
                 GYFDY 
                 ID 
                 NFLAW 
                 ID 
                 NRL 
                 ID 
                 PRTF 
               
               
                 464 
                   
                 517 
                 SVKS 
                 578 
                   
                 685 
                   
                 758 
                 SG 
                 815 
                   
               
               
                   
               
               
                 SEQ 
                 GFTFS 
                 SEQ 
                 LIYWDDD 
                 SEQ 
                 GIYDSSGSSN 
                 SEQ 
                 ASQSIGS 
                 SEQ 
                 GAS 
                 SEQ 
                 YGSS 
               
               
                 ID 
                 SSAMH 
                 ID 
                 KRYSPSLK 
                 ID 
                 PFDS 
                 ID 
                 NLAW 
                 ID 
                 RRA 
                 ID 
                 PPGT 
               
               
                 465 
                   
                 518 
                 S 
                 579 
                   
                 686 
                   
                 759 
                 TG 
                 816 
                 P 
               
               
                   
               
               
                 SEQ 
                 GDSVS 
                 SEQ 
                 YIYYTGST 
                 SEQ 
                 GYCSGGSCP 
                 SEQ 
                 ASQSVGN 
                 SEQ 
                 EVS 
                 SEQ 
                 YHN 
               
               
                 ID 
                 SDSAV 
                 ID 
                 NYNPSLKS 
                 ID 
                 GTDFDY 
                 ID 
                 SLAW 
                 ID 
                 NRF 
                 ID 
                 WPPY 
               
               
                 466 
                 WT 
                 519 
                   
                 580 
                   
                 687 
                   
                 760 
                 SG 
                 817 
                 IF 
               
               
                   
               
               
                 SEQ 
                 GFTFS 
                 SEQ 
                 MIWHDES 
                 SEQ 
                 DGVGGRDG 
                 SEQ 
                 ASQSITN 
                 SEQ 
                 AAS 
                 SEQ 
                 YNSY 
               
               
                 ID 
                 TYPM 
                 ID 
                 KKYYADS 
                 ID 
                 YNFDY 
                 ID 
                 WLAW 
                 ID 
                 YRA 
                 ID 
                 WTF 
               
               
                 467 
                 H 
                 520 
                 VKG 
                 581 
                   
                 688 
                   
                 761 
                 IG 
                 818 
                   
               
               
                   
               
               
                 SEQ 
                 GFTFA 
                 SEQ 
                 RTYYKSK 
                 SEQ 
                 APLAADGYF 
                 SEQ 
                 ARQSISN 
                 SEQ 
                 GAS 
                 SEQ 
                 YAA 
               
               
                 ID 
                 AYNIN 
                 ID 
                 WYNDYAA 
                 ID 
                 DY 
                 ID 
                 RLAW 
                 ID 
                 SRA 
                 ID 
                 APITF 
               
               
                 468 
                   
                 521 
                 SVKS 
                 582 
                   
                 689 
                   
                 762 
                 SG 
                 819 
                   
               
               
                   
               
               
                 SEQ 
                 GFTFS 
                 SEQ 
                 VISYDGRN 
                 SEQ 
                 ARGLQYLIW 
                 SEQ 
                 ASQNVYS 
                 SEQ 
                 KAS 
                 SEQ 
                 YNSV 
               
               
                 ID 
                 SYGM 
                 ID 
                 EYYADSV 
                 ID 
                 YFDL 
                 ID 
                 NFLAW 
                 ID 
                 TIKS 
                 ID 
                 PLTF 
               
               
                 469 
                 T 
                 522 
                 KG 
                 583 
                   
                 690 
                   
                 763 
                 G 
                 820 
                   
               
               
                   
               
               
                 SEQ 
                 GYTFT 
                 SEQ 
                 FISYDGSN 
                 SEQ 
                 PGMVRGVIT 
                 SEQ 
                 SSQSLEH 
                 SEQ 
                 AAS 
                 SEQ 
                 YYNL 
               
               
                 ID 
                 GYYM 
                 ID 
                 KYYADSV 
                 ID 
                 APLDY 
                 ID 
                 GDGNTY 
                 ID 
                 NLH 
                 ID 
                 PRSF 
               
               
                 470 
                 H 
                 523 
                 KG 
                 584 
                   
                 691 
                 LSW 
                 764 
                 SG 
                 821 
                   
               
               
                   
               
               
                 SEQ 
                 GYTLT 
                 SEQ 
                 FIRANADS 
                 SEQ 
                 EAKWGMYY 
                 SEQ 
                 ASQSVSS 
                 SEQ 
                 LGS 
                 SEQ 
                 YAST 
               
               
                 ID 
                 ELSMH 
                 ID 
                 GTTEYAAS 
                 ID 
                 FDY 
                 ID 
                 TSLAW 
                 ID 
                 NRA 
                 ID 
                 PYTF 
               
               
                 471 
                   
                 524 
                 VKG 
                 585 
                   
                 692 
                   
                 765 
                 PG 
                 822 
                   
               
               
                   
               
               
                 SEQ 
                 GFTFS 
                 SEQ 
                 TISGNGVG 
                 SEQ 
                 GGGASYTDS 
                 SEQ 
                 ASQSVGS 
                 SEQ 
                 RAS 
                 SEQ 
                 YNN 
               
               
                 ID 
                 DQYM 
                 ID 
                 TYYPDSVK 
                 ID 
                   
                 ID 
                 KLAW 
                 ID 
                 SRA 
                 ID 
                 WFLT 
               
               
                 472 
                 D 
                 525 
                 D 
                 586 
                   
                 693 
                   
                 766 
                 IG 
                 823 
                 P 
               
               
                   
               
               
                 SEQ 
                 GFTFG 
                 SEQ 
                 WINPNSGG 
                 SEQ 
                 KGGYVGYSY 
                 SEQ 
                 SSQSLLG 
                 SEQ 
                 EVS 
                 SEQ 
                 RSN 
               
               
                 ID 
                 DYAM 
                 ID 
                 TNYAQKF 
                 ID 
                 GPFGGY 
                 ID 
                 GDGKTY 
                 ID 
                 NRD 
                 ID 
                 WSLT 
               
               
                 473 
                 S 
                 526 
                 QG 
                 587 
                   
                 694 
                 LYW 
                 767 
                 SG 
                 824 
                 P 
               
               
                   
               
               
                 SEQ 
                 GFNFS 
                 SEQ 
                 GFDPEDGE 
                 SEQ 
                 GGTMVRGFG 
                 SEQ 
                 ASQSVSS 
                 SEQ 
                 RAS 
                 SEQ 
                 YGPS 
               
               
                 ID 
                 GYEM 
                 ID 
                 TIYAQKFQ 
                 ID 
                 FNY 
                 ID 
                 NSLAW 
                 ID 
                 TRA 
                 ID 
                 RRITF 
               
               
                 474 
                 N 
                 527 
                 G 
                 588 
                   
                 695 
                   
                 768 
                 AG 
                 825 
                   
               
               
                   
               
               
                 SEQ 
                 RFTFS 
                 SEQ 
                 RVRNKAN 
                 SEQ 
                 ARRAMIGPL 
                 SEQ 
                 SSQSLVY 
                 SEQ 
                 RAS 
                 SEQ 
                 HGE 
               
               
                 ID 
                 DAWM 
                 ID 
                 SYTTEYAA 
                 ID 
                 PRLVGYFDL 
                 ID 
                 SDGNTYL 
                 ID 
                 RLE 
                 ID 
                 WPTF 
               
               
                 475 
                 S 
                 528 
                 SVKG 
                 589 
                   
                 696 
                 NW 
                 769 
                 SG 
                 826 
                   
               
               
                   
               
               
                 SEQ 
                 GFTFS 
                 SEQ 
                 AISSNGGS 
                 SEQ 
                 GRPAPSWVK 
                 SEQ 
                 ASQSISR 
                 SEQ 
                 DSN 
                 SEQ 
                 RGT 
               
               
                 ID 
                 TYGM 
                 ID 
                 TYYADSV 
                 ID 
                 TRNWFDP 
                 ID 
                 WLAW 
                 ID 
                 RAT 
                 ID 
                 WPPL 
               
               
                 476 
                 H 
                 529 
                 KG 
                 590 
                   
                 697 
                   
                 770 
                 G 
                 827 
                 IF 
               
               
                   
               
               
                 SEQ 
                 GISFR 
                 SEQ 
                 YVSTSGST 
                 SEQ 
                 EASSGWN 
                 SEQ 
                 PSQDIGT 
                 SEQ 
                 KVS 
                 SEQ 
                 YTNY 
               
               
                 ID 
                 DYWM 
                 ID 
                 RYYADSV 
                 ID 
                   
                 ID 
                 YLNW 
                 ID 
                 KRD 
                 ID 
                 PRTF 
               
               
                 477 
                 H 
                 530 
                 KG 
                 591 
                   
                 698 
                   
                 771 
                 SG 
                 828 
                   
               
               
                   
               
               
                 SEQ 
                 GDSVS 
                 SEQ 
                 GISGSGGS 
                 SEQ 
                 GGRYTKGGY 
                 SEQ 
                 ASQSISSC 
                 SEQ 
                 KAS 
                 SEQ 
                 YQSY 
               
               
                 ID 
                 SKSAA 
                 ID 
                 TYYADSV 
                 ID 
                 FDD 
                 ID 
                 LAW 
                 ID 
                 SLT 
                 ID 
                 WTF 
               
               
                 478 
                 WN 
                 531 
                 KG 
                 592 
                   
                 699 
                   
                 772 
                 SG 
                 829 
                   
               
               
                   
               
               
                 SEQ 
                 GDSVS 
                 SEQ 
                 RIKSKISGG 
                 SEQ 
                 RLDSSGRGG 
                 SEQ 
                 SSQSLLH 
                 SEQ 
                 DSS 
                 SEQ 
                 YNSP 
               
               
                 ID 
                 SGSAA 
                 ID 
                 TTDYAAP 
                 ID 
                 YFDY 
                 ID 
                 SDGKTYL 
                 ID 
                 NRA 
                 ID 
                 PRTF 
               
               
                 479 
                 WN 
                 532 
                 VQG 
                 593 
                   
                 700 
                 YW 
                 773 
                 TG 
                 830 
                   
               
               
                   
               
               
                 SEQ 
                 EFTLR 
                 SEQ 
                 RTYYRSK 
                 SEQ 
                 ELVGTSSPYY 
                 SEQ 
                 SSQSVLY 
                 SEQ 
                 GVS 
                 SEQ 
                 YGTS 
               
               
                 ID 
                 NYGVS 
                 ID 
                 WYNDYAV 
                 ID 
                 YYYYGMDV 
                 ID 
                 SSNNKNY 
                 ID 
                 TRA 
                 ID 
                 PITF 
               
               
                 480 
                   
                 533 
                 SLKS 
                 594 
                   
                 701 
                 IAW 
                 774 
                 TG 
                 831 
                   
               
               
                   
               
               
                 SEQ 
                 GGSVS 
                 SEQ 
                 LISYDGSK 
                 SEQ 
                 DYYYGSGSS 
                 SEQ 
                 ASQSLTS 
                 SEQ 
                 GAS 
                 SEQ 
                 GIYW 
               
               
                 ID 
                 GYYW 
                 ID 
                 KYYANSV 
                 ID 
                 P 
                 ID 
                 SYLAW 
                 ID 
                 SRA 
                 ID 
                 PRTF 
               
               
                 481 
                 S 
                 534 
                 KG 
                 595 
                   
                 702 
                   
                 775 
                 TD 
                 832 
                   
               
               
                   
               
               
                 SEQ 
                 GDSVS 
                 SEQ 
                 WINAGNG 
                 SEQ 
                 GRPYCSSTSC 
                 SEQ 
                 SSQSLVH 
                 SEQ 
                 GTS 
                 SEQ 
                 YGSS 
               
               
                 ID 
                 SNTAT 
                 ID 
                 NTKYSEKF 
                 ID 
                 YPEWFDP 
                 ID 
                 SNGHTYL 
                 ID 
                 TRA 
                 ID 
                 PPITF 
               
               
                 482 
                 WN 
                 535 
                 EG 
                 596 
                   
                 703 
                 SW 
                 776 
                 TG 
                 833 
                   
               
               
                   
               
               
                 SEQ 
                 GDSVS 
                 SEQ 
                 RINPDGSS 
                 SEQ 
                 LRGIDYYDSS 
                 SEQ 
                 ASQSVGS 
                 SEQ 
                 DAS 
                 SEQ 
                 YNN 
               
               
                 ID 
                 GNSAA 
                 ID 
                 TSYADSVK 
                 ID 
                 GYQRGFDY 
                 ID 
                 DLAW 
                 ID 
                 NLE 
                 ID 
                 WPPI 
               
               
                 483 
                 WN 
                 536 
                 G 
                 597 
                   
                 704 
                   
                 777 
                 TG 
                 834 
                 TF 
               
               
                   
               
               
                 SEQ 
                 GYTFT 
                 SEQ 
                 RTYYRSK 
                 SEQ 
                 GGRGDGAAF 
                 SEQ 
                 SSQSLLH 
                 SEQ 
                 AAS 
                 SEQ 
                 TLQT 
               
               
                 ID 
                 SYAIS 
                 ID 
                 WNNDYAL 
                 ID 
                 DI 
                 ID 
                 SSGYNYL 
                 ID  
                 SLQ 
                 ID 
                 PLTF 
               
               
                 484 
                   
                 537 
                 SVKS 
                 598 
                   
                 705 
                 DW 
                 778 
                 SG 
                 835 
                   
               
               
                   
               
               
                 SEQ 
                 GFIFSN 
                 SEQ 
                 RTYYRAK 
                 SEQ 
                 PPDGGNSGR 
                 SEQ 
                 ASQTINS 
                 SEQ 
                 EVS 
                 SEQ 
                 YYSS 
               
               
                 ID 
                 YAIH 
                 ID 
                 WYNEYAG 
                 ID 
                 WYFDL 
                 ID 
                 WLAW 
                 ID 
                 KRD 
                 ID 
                 TPYT 
               
               
                 485 
                   
                 538 
                 SVKS 
                 599 
                   
                 706 
                   
                 779 
                 SG 
                 836 
                 F 
               
               
                   
               
               
                   
                   
                 SEQ 
                 GMSGSGY 
                 SEQ 
                 DKNVRKHD 
                 SEQ 
                 ASQTIGP 
                 SEQ 
                 WAS 
                 SEQ 
                 STQF 
               
               
                   
                   
                 ID 
                 STYYADSV 
                 ID 
                 YGDHPYGGY 
                 ID 
                 KSFGW 
                 ID 
                 TRG 
                 ID 
                 PWTF 
               
               
                   
                   
                 539 
                 KG 
                 600 
                 FDY 
                 707 
                   
                 780 
                 SG 
                 837 
                   
               
               
                   
               
               
                   
                   
                 SEQ 
                 EIHHSGST 
                 SEQ 
                 VAGATSLWY 
                 SEQ 
                 SSQSLVY 
                 SEQ 
                 KIS 
                 SEQ 
                 YNN 
               
               
                   
                   
                 ID 
                 NYNPSLKS 
                 ID 
                   
                 ID 
                 SDGNTYL 
                 ID 
                 NRF 
                 ID 
                 WPHT 
               
               
                   
                   
                 540 
                   
                 601 
                   
                 708 
                 YW 
                 781 
                 SG 
                 838 
                 F 
               
               
                   
               
               
                   
                   
                 SEQ 
                 RTYYRSK 
                 SEQ 
                 LANSDGVDV 
                 SEQ 
                 ASQSITT 
                 SEQ 
                 KAS 
                 SEQ 
                 YGNS 
               
               
                   
                   
                 ID 
                 WYKDNAL 
                 ID 
                   
                 ID 
                 WLAW 
                 ID 
                 SLE 
                 ID 
                 QTF 
               
               
                   
                   
                 541 
                 SVKS 
                 602 
                   
                 709 
                   
                 782 
                 SG 
                 839 
                   
               
               
                   
               
               
                   
                   
                 SEQ 
                 LIYSDGRT 
                 SEQ 
                 GVTRTFDY 
                 SEQ 
                 ASQSIGT 
                 SEQ 
                 GAS 
                 SEQ 
                 GTH 
               
               
                   
                   
                 ID 
                 NYADSVK 
                 ID 
                   
                 ID 
                 YVAW 
                 ID 
                 TRA 
                 ID 
                 WPRT 
               
               
                   
                   
                 542 
                 G 
                 603 
                   
                 710 
                   
                 783 
                 TA 
                 840 
                 F 
               
               
                   
               
               
                   
                   
                 SEQ 
                 AISSNGGS 
                 SEQ 
                 GNGPFDP 
                 SEQ 
                 ASQSVNS 
                   
                   
                 SEQ 
                 YKSD 
               
               
                   
                   
                 ID 
                 TYYANSV 
                 ID 
                   
                 ID 
                 GYLAW 
                   
                   
                 ID 
                 SRTF 
               
               
                   
                   
                 543 
                 KG 
                 604 
                   
                 711 
                   
                   
                   
                 841 
                   
               
               
                   
               
               
                   
                   
                 SEQ 
                 WISAYDG 
                 SEQ 
                 RDTPLVGVSI 
                 SEQ 
                 ASQSVSS 
                   
                   
                 SEQ 
                 SYGP 
               
               
                   
                   
                 ID 
                 NTNYAQK 
                 ID 
                 Y 
                 ID 
                 SYLGW 
                   
                   
                 ID 
                 RTF 
               
               
                   
                   
                 544 
                 LQG 
                 605 
                   
                 712 
                   
                   
                   
                 842 
                   
               
               
                   
               
               
                   
                   
                 SEQ 
                 YISSSGTTI 
                 SEQ 
                 RAGYGDYRH 
                 SEQ 
                 ASQSISN 
                   
                   
                 SEQ 
                 YGSS 
               
               
                   
                   
                 ID 
                 YYADSVK 
                 ID 
                 FQH 
                 ID 
                 NLAW 
                   
                   
                 ID 
                 GYTF 
               
               
                   
                   
                 545 
                 G 
                 606 
                   
                 713 
                   
                   
                   
                 843 
                   
               
               
                   
               
               
                   
                   
                 SEQ 
                 VIWYDGS 
                 SEQ 
                 TGDRFQEFD 
                 SEQ 
                 ASQSVSS 
                   
                   
                 SEQ 
                 YGSS 
               
               
                   
                   
                 ID 
                 NKYYADS 
                 ID 
                 Y 
                 ID 
                 SSLAW 
                   
                   
                 ID 
                 P 
               
               
                   
                   
                 546 
                 VKG 
                 607 
                   
                 714 
                   
                   
                   
                 844 
                   
               
               
                   
               
               
                   
                   
                   
                   
                 SEQ 
                 DDRGRGDDF 
                 SEQ 
                 SNQSLVY 
                   
                   
                 SEQ 
                 LNSY 
               
               
                   
                   
                   
                   
                 ID 
                 DY 
                 ID 
                 SDGGTYL 
                   
                   
                 ID 
                 PQTF 
               
               
                   
                   
                   
                   
                 608 
                   
                 715 
                 NW 
                   
                   
                 845 
                   
               
               
                   
               
               
                   
                   
                   
                   
                 SEQ 
                 HGRAGINWY 
                 SEQ 
                 ASQSISN 
                   
                   
                 SEQ 
                 SIQLP 
               
               
                   
                   
                   
                   
                 ID 
                 FDL 
                 ID 
                 YLNW 
                   
                   
                 ID 
                 LTF 
               
               
                   
                   
                   
                   
                 609 
                   
                 716 
                   
                   
                   
                 846 
                   
               
               
                   
               
               
                   
                   
                   
                   
                 SEQ 
                 GGGLWAFDI 
                 SEQ 
                 ASQSVST 
                   
                   
                 SEQ 
                 YYYI 
               
               
                   
                   
                   
                   
                 ID 
                   
                 ID 
                 LLAW 
                   
                   
                 ID 
                 PRTF 
               
               
                   
                   
                   
                   
                 610 
                   
                 717 
                   
                   
                   
                 847 
                   
               
               
                   
               
               
                   
                   
                   
                   
                 SEQ 
                 DKIGSCPY 
                 SEQ 
                 ASQGIRN 
                   
                   
                 SEQ 
                 ALQT 
               
               
                   
                   
                   
                   
                 ID 
                   
                 ID 
                 DLGW 
                   
                   
                 ID 
                 RTF 
               
               
                   
                   
                   
                   
                 611 
                   
                 718 
                   
                   
                   
                 848 
                   
               
               
                   
               
               
                   
                   
                   
                   
                 SEQ 
                 RPDSSSQCFD 
                 SEQ 
                 SSHSLTT 
                   
                   
                 SEQ 
                 YGSS 
               
               
                   
                   
                   
                   
                 ID 
                 Y 
                 ID 
                 TDGRTYV 
                   
                   
                 ID 
                 PNTF 
               
               
                   
                   
                   
                   
                 612 
                   
                 719 
                 AW 
                   
                   
                 849 
                   
               
               
                   
               
               
                   
                   
                   
                   
                 SEQ 
                 SSGWSLPED 
                 SEQ 
                 ASQSVTS 
                   
                   
                 SEQ 
                 GTH 
               
               
                   
                   
                   
                   
                 ID 
                 Y 
                 ID 
                 NLAW 
                   
                   
                 ID 
                 WPPL 
               
               
                   
                   
                   
                   
                 613 
                   
                 720 
                   
                   
                   
                 850 
                 TV 
               
               
                   
               
               
                   
                   
                   
                   
                 SEQ 
                 DVNPELLGA 
                 SEQ 
                 ASQSVFN 
                   
                   
                 SEQ 
                 YGRS 
               
               
                   
                   
                   
                   
                 ID 
                 GFDY 
                 ID 
                 NYLAW 
                   
                   
                 ID 
                 PYTS 
               
               
                   
                   
                   
                   
                 614 
                   
                 721 
                   
                   
                   
                 851 
                   
               
               
                   
               
               
                   
                   
                   
                   
                 SEQ 
                 SLNSGGYRC 
                 SEQ 
                 SSQSVLY 
                   
                   
                 SEQ 
                 YYST 
               
               
                   
                   
                   
                   
                 ID 
                 FHH 
                 ID 
                 DSNSKNY 
                   
                   
                 ID 
                 PLTF 
               
               
                   
                   
                   
                   
                 615 
                   
                 722 
                 LSW 
                   
                   
                 852 
                   
               
               
                   
               
               
                   
                   
                   
                   
                 SEQ 
                 APRGVVPAA 
                 SEQ 
                 ASQSVGT 
                   
                   
                 SEQ 
                 GLQI 
               
               
                   
                   
                   
                   
                 ID 
                 MRGGY 
                 ID 
                 NLAW 
                   
                   
                 ID 
                 PLTF 
               
               
                   
                   
                   
                   
                 616 
                   
                 723 
                   
                   
                   
                 853 
                   
               
               
                   
               
               
                   
                   
                   
                   
                 SEQ 
                 LVGNSGSYY 
                 SEQ 
                 SSQSLVY 
                   
                   
                 SEQ 
                 SIQLP 
               
               
                   
                   
                   
                   
                 ID 
                 PFGY 
                 ID 
                 SDGNTYL 
                   
                   
                 ID 
                 WTF 
               
               
                   
                   
                   
                   
                 617 
                   
                 724 
                 SW 
                   
                   
                 854 
                   
               
               
                   
               
               
                   
                   
                   
                   
                 SEQ 
                 GRSLPYRGL 
                 SEQ 
                 ASQSVIS 
                   
                   
                 SEQ 
                 YNN 
               
               
                   
                   
                   
                   
                 ID 
                 APRSFGGYY 
                 ID 
                 RYLAW 
                   
                   
                 ID 
                 WPRF 
               
               
                   
                   
                   
                   
                 618 
                 FDY 
                 725 
                   
                   
                   
                 855 
                   
               
               
                   
               
               
                   
                   
                   
                   
                 SEQ 
                 GRTHWGPQD 
                 SEQ 
                 ASQSVSS 
                   
                   
                 SEQ 
                 YNSY 
               
               
                   
                   
                   
                   
                 ID 
                 FDY 
                 ID 
                 SLAW 
                   
                   
                 ID 
                 SPTF 
               
               
                   
                   
                   
                   
                 619 
                   
                 726 
                   
                   
                   
                 856 
                   
               
               
                   
               
               
                   
                   
                   
                   
                 SEQ 
                 GGMYYYGS 
                   
                   
                   
                   
                 SEQ 
                 RYN 
               
               
                   
                   
                   
                   
                 ID 
                 GSSYFDY 
                   
                   
                   
                   
                 ID 
                 WPIT 
               
               
                   
                   
                   
                   
                 620 
                   
                   
                   
                   
                   
                 857 
                 F 
               
               
                   
               
               
                   
                   
                   
                   
                 SEQ 
                 KIAAAGKQP 
                   
                   
                   
                   
                 SEQ 
                 RSRW 
               
               
                   
                   
                   
                   
                 ID 
                 VDY 
                   
                   
                   
                   
                 ID 
                 PLTF 
               
               
                   
                   
                   
                   
                 621 
                   
                   
                   
                   
                   
                 858 
                   
               
               
                   
               
               
                   
                   
                   
                   
                 SEQ 
                 RKVYDYVW 
                   
                   
                   
                   
                 SEQ 
                 GRH 
               
               
                   
                   
                   
                   
                 ID 
                 GSYRLPGSVS 
                   
                   
                   
                   
                 ID 
                 WPYT 
               
               
                   
                   
                   
                   
                 622 
                 YYFDY 
                   
                   
                   
                   
                 859 
                 L 
               
               
                   
               
               
                   
                   
                   
                   
                 SEQ 
                 LPGRAARPD 
                   
                   
                   
                   
                 SEQ 
                 YNSY 
               
               
                   
                   
                   
                   
                 ID 
                 Y 
                   
                   
                   
                   
                 ID 
                 SRTF 
               
               
                   
                   
                   
                   
                 623 
                   
                   
                   
                   
                   
                 860 
                   
               
               
                   
               
               
                   
                   
                   
                   
                 SEQ 
                 GPGAVAGTK 
                   
                   
                   
                   
                 SEQ 
                 YNG 
               
               
                   
                   
                   
                   
                 ID 
                 PKYYFDY 
                   
                   
                   
                   
                 ID 
                 ASRM 
               
               
                   
                   
                   
                   
                 624 
                   
                   
                   
                   
                   
                 861 
                 F 
               
               
                   
               
               
                   
                   
                   
                   
                 SEQ 
                 ATYYYDSSG 
                   
                   
                   
                   
                 SEQ 
                 RSN 
               
               
                   
                   
                   
                   
                 ID 
                 YRFDY 
                   
                   
                   
                   
                 ID 
                 WPFF 
               
               
                   
                   
                   
                   
                 625 
                   
                   
                   
                   
                   
                 862 
                   
               
               
                   
               
               
                   
                   
                   
                   
                 SEQ 
                 RNLGY 
                   
                   
                   
                   
                 SEQ 
                 RAE 
               
               
                   
                   
                   
                   
                 ID 
                   
                   
                   
                   
                   
                 ID 
                 WPLT 
               
               
                   
                   
                   
                   
                 626 
                   
                   
                   
                   
                   
                 863 
                 F 
               
               
                   
               
               
                   
                   
                   
                   
                 SEQ 
                 ARYYDSSGY 
                   
                   
                   
                   
                 SEQ 
                 YGNS 
               
               
                   
                   
                   
                   
                 ID 
                 IAPSGYFDY 
                   
                   
                   
                   
                 ID 
                 AMY 
               
               
                   
                   
                   
                   
                 627 
                   
                   
                   
                   
                   
                 864 
                 NF 
               
               
                   
               
               
                   
                   
                   
                   
                 SEQ 
                 DGPAVDGAE 
                   
                   
                   
                   
                 SEQ 
                 YNN 
               
               
                   
                   
                   
                   
                 ID 
                 YFQH 
                   
                   
                   
                   
                 ID 
                 WPPF 
               
               
                   
                   
                   
                   
                 628 
                   
                   
                   
                   
                   
                 865 
                 TF 
               
               
                   
               
               
                   
                   
                   
                   
                 SEQ 
                 LASGSPPPGD 
                   
                   
                   
                   
                 SEQ 
                 YGIS 
               
               
                   
                   
                   
                   
                 ID 
                 Y 
                   
                   
                   
                   
                 ID 
                 PLAF 
               
               
                   
                   
                   
                   
                 629 
                   
                   
                   
                   
                   
                 866 
                   
               
               
                   
               
               
                   
                   
                   
                   
                 SEQ 
                 GPIVGATMD 
                   
                   
                   
                   
                 SEQ 
                 YNF 
               
               
                   
                   
                   
                   
                 ID 
                 Y 
                   
                   
                   
                   
                 ID 
                 WPSI 
               
               
                   
                   
                   
                   
                 630 
                   
                   
                   
                   
                   
                 867 
                 TF 
               
               
                   
               
               
                   
                   
                   
                   
                 SEQ 
                 WYGDYGLD 
                   
                   
                   
                   
                 SEQ 
                 YGSS 
               
               
                   
                   
                   
                   
                 ID 
                 Y 
                   
                   
                   
                   
                 ID 
                 QTF 
               
               
                   
                   
                   
                   
                 631 
                   
                   
                   
                   
                   
                 868 
                   
               
               
                   
               
               
                   
                   
                   
                   
                 SEQ 
                 VAKYYYESG 
                   
                   
                   
                   
                 SEQ 
                 GTH 
               
               
                   
                   
                   
                   
                 ID 
                 GYRASNWFD 
                   
                   
                   
                   
                 ID 
                 WPYT 
               
               
                   
                   
                   
                   
                 632 
                 P 
                   
                   
                   
                   
                 869 
                 F 
               
               
                   
               
               
                   
                   
                   
                   
                 SEQ 
                 APPPTVGWY 
                   
                   
                   
                   
                 SEQ 
                 FDNV 
               
               
                   
                   
                   
                   
                 ID 
                 APVFDY 
                   
                   
                   
                   
                 ID 
                 PVTF 
               
               
                   
                   
                   
                   
                 633 
                   
                   
                   
                   
                   
                 870 
                   
               
               
                   
               
               
                   
                   
                   
                   
                 SEQ 
                 VTGRRVGAH 
                   
                   
                   
                   
                 SEQ 
                 YGSS 
               
               
                   
                   
                   
                   
                 ID 
                 DY 
                   
                   
                   
                   
                 ID 
                 SMYT 
               
               
                   
                   
                   
                   
                 634 
                   
                   
                   
                   
                   
                 871 
                 F 
               
               
                   
               
               
                   
                   
                   
                   
                 SEQ 
                 AQPGAETLN 
                   
                   
                   
                   
                 SEQ 
                 SYITP 
               
               
                   
                   
                   
                   
                 ID 
                 FDL 
                   
                   
                   
                   
                 ID 
                 WTP 
               
               
                   
                   
                   
                   
                 635 
                   
                   
                   
                   
                   
                 872 
                   
               
               
                   
               
               
                   
                   
                   
                   
                 SEQ 
                 QVAGGMDV 
                   
                   
                   
                   
                 SEQ 
                 RYV 
               
               
                   
                   
                   
                   
                 ID 
                   
                   
                   
                   
                   
                 ID 
                 WPFT 
               
               
                   
                   
                   
                   
                 636 
                   
                   
                   
                   
                   
                 873 
                 F 
               
               
                   
               
               
                   
                   
                   
                   
                 SEQ 
                 GSVYSGSYY 
                   
                   
                   
                   
                 SEQ 
                 HNSY 
               
               
                   
                   
                   
                   
                 ID 
                 MLIDY 
                   
                   
                   
                   
                 ID 
                 PRTF 
               
               
                   
                   
                   
                   
                 637 
                   
                   
                   
                   
                   
                 874 
                   
               
               
                   
               
               
                   
                   
                   
                   
                 SEQ 
                 QDKDNTRYS 
                   
                   
                   
                   
                 SEQ 
                 RSN 
               
               
                   
                   
                   
                   
                 ID 
                 GLGV 
                   
                   
                   
                   
                 ID 
                 WPW 
               
               
                   
                   
                   
                   
                 638 
                   
                   
                   
                   
                   
                 875 
                 TF 
               
               
                   
               
               
                   
                   
                   
                   
                 SEQ 
                 GPRMWSSGI 
                   
                   
                   
                   
                 SEQ 
                 GTHG 
               
               
                   
                   
                   
                   
                 ID 
                 DAFDI 
                   
                   
                   
                   
                 ID 
                 PHTF 
               
               
                   
                   
                   
                   
                 639 
                   
                   
                   
                   
                   
                 876 
                   
               
               
                   
               
               
                   
                   
                   
                   
                 SEQ 
                 RDWAGKRV 
                   
                   
                   
                   
                 SEQ 
                 YGSP 
               
               
                   
                   
                   
                   
                 ID 
                   
                   
                   
                   
                   
                 ID 
                 PPTT 
               
               
                   
                   
                   
                   
                 640 
                   
                   
                   
                   
                   
                 877 
                 F 
               
               
                   
               
               
                   
                   
                   
                   
                 SEQ 
                 GRAGIAAFDI 
                   
                   
                   
                   
                 SEQ 
                 YGSS 
               
               
                   
                   
                   
                   
                 ID 
                   
                   
                   
                   
                   
                 ID 
                 RRTF 
               
               
                   
                   
                   
                   
                 641 
                   
                   
                   
                   
                   
                 878 
                   
               
               
                   
               
               
                   
                   
                   
                   
                 SEQ 
                 GALQGEWRR 
                   
                   
                   
                   
                 SEQ 
                 YGSS 
               
               
                   
                   
                   
                   
                 ID 
                 FDY 
                   
                   
                   
                   
                 ID 
                 PITF 
               
               
                   
                   
                   
                   
                 642 
                   
                   
                   
                   
                   
                 879 
                   
               
               
                   
               
               
                   
                   
                   
                   
                 SEQ 
                 TNQGYGGNS 
                   
                   
                   
                   
                 SEQ 
                 YGSS 
               
               
                   
                   
                   
                   
                 ID 
                 GVFDY 
                   
                   
                   
                   
                 ID 
                 LRYT 
               
               
                   
                   
                   
                   
                 643 
                   
                   
                   
                   
                   
                 880 
                 F 
               
               
                   
               
               
                   
                   
                   
                   
                 SEQ 
                 IVGGAVDC 
                   
                   
                   
                   
                 SEQ 
                 FYGI 
               
               
                   
                   
                   
                   
                 ID 
                   
                   
                   
                   
                   
                 ID 
                 PHF 
               
               
                   
                   
                   
                   
                 644 
                   
                   
                   
                   
                   
                 881 
                   
               
               
                   
               
               
                   
                   
                   
                   
                 SEQ 
                 VRVGATTVY 
                   
                   
                   
                   
                 SEQ 
                 GTQF 
               
               
                   
                   
                   
                   
                 ID 
                 DSWFDP 
                   
                   
                   
                   
                 ID 
                 PQTF 
               
               
                   
                   
                   
                   
                 645 
                   
                   
                   
                   
                   
                 882 
                   
               
               
                   
               
               
                   
                   
                   
                   
                 SEQ 
                 DGGSSPYYD 
                   
                   
                   
                   
                 SEQ 
                 YGSS 
               
               
                   
                   
                   
                   
                 ID 
                 SSGLLPWYF 
                   
                   
                   
                   
                 ID 
                 PPYT 
               
               
                   
                   
                   
                   
                 646 
                 DL 
                   
                   
                   
                   
                 883 
                 F 
               
               
                   
               
               
                   
                   
                   
                   
                 SEQ 
                 AKFWTYYFD 
                   
                   
                   
                   
                 SEQ 
                 YNSY 
               
               
                   
                   
                   
                   
                 ID 
                 Y 
                   
                   
                   
                   
                 ID 
                 SGTF 
               
               
                   
                   
                   
                   
                 647 
                   
                   
                   
                   
                   
                 884 
                   
               
               
                   
               
               
                   
                   
                   
                   
                 SEQ 
                 GGGSGSYYK 
                   
                   
                   
                   
                 SEQ 
                 YDN 
               
               
                   
                   
                   
                   
                 ID 
                 RFFDY 
                   
                   
                   
                   
                 ID 
                 WPPL 
               
               
                   
                   
                   
                   
                 648 
                   
                   
                   
                   
                   
                 885 
                 F 
               
               
                   
               
               
                   
                   
                   
                   
                 SEQ 
                 DGTVRRVVG 
                   
                   
                   
                   
                   
                   
               
               
                   
                   
                   
                   
                 ID 
                 ATTPGNFDY 
                   
                   
                   
                   
                   
                   
               
               
                   
                   
                   
                   
                 649 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                   
                   
                   
                   
                 SEQ 
                 DLNRGYCSG 
                   
                   
                   
                   
                   
                   
               
               
                   
                   
                   
                   
                 ID 
                 GSCFGY 
                   
                   
                   
                   
                   
                   
               
               
                   
                   
                   
                   
                 650 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                   
                   
                   
                   
                 SEQ 
                 DYSSSGECFD 
                   
                   
                   
                   
                   
                   
               
               
                   
                   
                   
                   
                 ID 
                 Y 
                   
                   
                   
                   
                   
                   
               
               
                   
                   
                   
                   
                 651 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                   
                   
                   
                   
                 SEQ 
                 DQAAMVGY 
                   
                   
                   
                   
                   
                   
               
               
                   
                   
                   
                   
                 ID 
                 FDY 
                   
                   
                   
                   
                   
                   
               
               
                   
                   
                   
                   
                 652 
                   
                   
                   
                   
                   
                   
                   
               
               
                   
               
               
                   
                   
                   
                   
                 SEQ 
                 TFAGYSSKL 
                   
                   
                   
                   
                   
                   
               
               
                   
                   
                   
                   
                 ID 
                 GYFDL 
                   
                   
                   
                   
                   
                   
               
               
                   
                   
                   
                   
                 653 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 7 
               
             
            
               
                   
               
               
                 Heavy Chain CDR DNA Sequences 
               
            
           
           
               
               
               
               
               
               
            
               
                 SEQ ID 
                 CDRH1 DNA Seq 
                 SEQ ID 
                 CDRH2 DNA Seq 
                 SEQ ID 
                 CDRH3 DNA Seq 
               
               
                   
               
               
                 SEQ ID 1004 
                 GGGGACAGTGTCTCTAG 
                 SEQ ID 
                 AGGACATACTACAGGTCCAAG 
                 SEQ ID 
                 GCCCGGCGGGCTATGATAGGGCCGC 
               
               
                   
                 CAACACTGCTACTTGGA 
                 1062 
                 TGGTATAAGGATAATGCACTGT 
                 1127 
                 TTCCGCGACTTGTCGGGTACTTCGA 
               
               
                   
                 AC 
                   
                 CTGTGAAAAGT 
                   
                 TCTC 
               
               
                   
               
               
                 SEQ ID 1005 
                 GGATTCACCTTCAGTTCC 
                 SEQ ID 
                 GTTATATCATATGATGGAACTA 
                 SEQ ID 
                 GGCCGCCCCGCCCCATCCTGGGTTA 
               
               
                   
                 CATCTTATGCAC 
                 1063 
                 GTAAATATTACGGAGACTCCGT 
                 1128 
                 AAACCCGTAACTGGTTCGACCCC 
               
               
                   
                   
                   
                 GAAGGGC 
                   
                   
               
               
                   
               
               
                 SEQ ID 1006 
                 GGGGACAGTGTCTCTAG 
                 SEQ ID 
                 AGGACATATTATAGGGCCAAG 
                 SEQ ID 
                 GGAGGAATGTATTACTATGGTTCGG 
               
               
                   
                 CGGCAGTGCTGCTTGGA 
                 1064 
                 TGGTATAATGAATATGCAGGG 
                 1129 
                 GGAGCTCGTACTTTGACTAC 
               
               
                   
                 AC 
                   
                 TCTGTGAAAAGC 
                   
                   
               
               
                   
               
               
                 SEQ ID 1007 
                 GGTTACACCTTTACCAGC 
                 SEQ ID 
                 TGGATCAGCGCTTACAATGGTA 
                 SEQ ID 
                 AGGAAGGTGTATGATTACGTTTGGG 
               
               
                   
                 TACGGTATCAGC 
                 1065 
                 ACACAAACTATGCACAGAAGC 
                 1130 
                 GGAGTTATCGCCTCCCCGGGTCGGT 
               
               
                   
                 TCCAGGGC 
                   
                 ATCGTACTACTTTGACTAC 
                   
                   
               
               
                   
               
               
                 SEQ ID 1008 
                 GGATTCACCTTCAGTAG 
                 SEQ ID 
                 CTCATTTATTGGGATGATGATA 
                 SEQ ID 
                 AAGGGGGGCTACGTCGGATACAGCT 
               
               
                   
                 CTATGCTATACAC 
                 1066 
                 AGCGCTACAGCCCATCTCTGAA 
                 1131 
                 ATGGACCTTTTGGGGGCTAC 
               
               
                   
                   
                   
                 GAGC 
                   
                   
               
               
                   
               
               
                 SEQ ID 1009 
                 GGGTTCTCACTCAGCACT 
                 SEQ ID 
                 TGGATGAACCCTAACAGTGGT 
                 SEQ ID 
                 GGTCGGGCTGGTATTGCCGCTTTTG 
               
               
                   
                 AGTGGAGTGGGTGTGGG 
                 1067 
                 AACACCGGCTATGCAGAGAAG 
                 1132 
                 ATATC 
               
               
                   
                 C 
                   
                 TTCCAGGGC 
                   
                   
               
               
                   
               
               
                 SEQ ID 1010 
                 GGATACACCTTCACCAG 
                 SEQ ID 
                 GTTATATCATATGATGGAAGTA 
                 SEQ ID 
                 GCAGATTATAAATATGACT 
               
               
                   
                 TTCTGATATCAAC 
                 1068 
                 ATAAATACTACGCAGACTCCGT 
                 1133 
                   
               
               
                   
                   
                   
                 GAAGGGC 
                   
                   
               
               
                   
               
               
                 SEQ ID 1011 
                 GGATTCACCTTCAGTAG 
                 SEQ ID 
                 ACTATTAGTGGTAATGGTGTTG 
                 SEQ ID 
                 AGCAGTGGCTGGTCACTGCCTGAAG 
               
               
                   
                 CTATGCTATGCAC 
                 1069 
                 GCACATACTACCCAGACTCCGT 
                 1134 
                 ACTAC 
               
               
                   
                   
                   
                 GAAGGAC 
                   
                   
               
               
                   
               
               
                 SEQ ID 1012 
                 GGATTCACCTTTAGCAG 
                 SEQ ID 
                 GTTATATGGTATGATGGAAGTA 
                 SEQ ID 
                 CAAGACAAAGACAACACGAGATAT 
               
               
                   
                 CTATGGCATGACG 
                 1070 
                 ATAAATACTATGCAGACTCCGT 
                 1135 
                 TCCGGTTTGGGCGTC 
               
               
                   
                   
                   
                 GAAGGGC 
                   
                   
               
               
                   
               
               
                 SEQ ID 1013 
                 GGATACACCTTCGCCGC 
                 SEQ ID 
                 CGGATCAGCCCTGGTAACGGT 
                 SEQ ID 
                 GCCGCGGTGGGGGATGGATACAGCT 
               
               
                   
                 CTATTATTTACAC 
                 1071 
                 GTCACAAGTTATGCACAGAAA 
                 1136 
                 ATGGTCGGCTCGATT 
               
               
                   
                   
                   
                 TTTCAGGGC 
                   
                   
               
               
                   
               
               
                 SEQ ID 1014 
                 GGATACACCTTCACCGG 
                 SEQ ID 
                 TGGATCAACCCTAACAGTGGT 
                 SEQ ID 
                 GATCAGGCAGCTATGGTAGGCTACT 
               
               
                   
                 CTACTATATGCAC 
                 1072 
                 GGCACAAACTATGCACAGAAG 
                 1137 
                 TTGACTAC 
               
               
                   
                   
                   
                 TTTCAGGGC 
                   
                   
               
               
                   
               
               
                 SEQ ID 1015 
                 GGATACACCTTCACCAG 
                 SEQ ID 
                 TGGATGAACCCTAACAGTGGT 
                 SEQ ID 
                 GGCCGGCCATATTGTAGTAGTACCA 
               
               
                   
                 TTATGATATCAAC 
                 1073 
                 AACACAGGCTATGCACAGAAG 
                 1138 
                 GCTGCTACCCAGAGTGGTTCGACCC 
               
               
                   
                   
                   
                 TTCCAGGGC 
                   
                 C 
               
               
                   
               
               
                 SEQ ID 1016 
                 GGATTCATCTTCAGTAAC 
                 SEQ ID 
                 CGTGTTAAAAACAAAGCTGAT 
                 SEQ ID 
                 AGATTGGATAGCAGTGGCCGTGGTG 
               
               
                   
                 TATGCTATACAC 
                 1074 
                 GGTGAGACAACGGACTACGCT 
                 1139 
                 GTTACTTTGACTAC 
               
               
                   
                   
                   
                 GCACCCGTCAAAGGC 
                   
                   
               
               
                   
               
               
                 SEQ ID 1017 
                 GGATTCACTTTCACTGAT 
                 SEQ ID 
                 GCTATTAGTGGTAGTGGTGGTA 
                 SEQ ID 
                 GACAAGAACGTCCGAAAACATGAC 
               
               
                   
                 GCCTGGATGAAC 
                 1075 
                 GCACATACTATGCAGACTCCGT 
                 1140 
                 TACGGTGACCACCCCTACGGGGGGT 
               
               
                   
                   
                   
                 GAAGGGC 
                   
                 ACTTTGACTAC 
               
               
                   
               
               
                 SEQ ID 1018 
                 GGTGGGTCCGTCAGTGG 
                 SEQ ID 
                 GAAATCCATCATAGTGGAAGC 
                 SEQ ID 
                 GAGTTGGTGGGTACCAGCTCTCCTT 
               
               
                   
                 TTACTACTGGAGC 
                 1076 
                 ACCAACTACAACCCGTCCCTCA 
                 1141 
                 ATTACTACTACTACTACGGTATGGA 
               
               
                   
                   
                   
                 AGAGT 
                   
                 CGTC 
               
               
                   
               
               
                 SEQ ID 1019 
                 GGATTCAACTTCAGTGG 
                 SEQ ID 
                 TACGTCAGTACTAGTGGTAGTA 
                 SEQ ID 
                 GGTGGGGGTGCGAGCTATACTGACT 
               
               
                   
                 ATATGAAATGAAC 
                 1077 
                 CCAGATACTACGCAGACTCTGT 
                 1142 
                 CC 
               
               
                   
                   
                   
                 GAAGGGC 
                   
                   
               
               
                   
               
               
                 SEQ ID 1020 
                 GGGGACAGTGTCTCTAG 
                 SEQ ID 
                 AGGACTTACTACCGGTCCCAGT 
                 SEQ ID 
                 TCGAGCCCCTGGGGGGAGTTATCGT 
               
               
                   
                 CAACAGTGTTACTTGGA 
                 1078 
                 GGTATTATAATTATGCGGTGTC 
                 1143 
                 TATACCAGGGGGCTTTTGATATC 
               
               
                   
                 AC 
                   
                 TGTGAAAAGT 
                   
                   
               
               
                   
               
               
                 SEQ ID 1021 
                 GGATTCACCTTCAGCAG 
                 SEQ ID 
                 CGTATTAATCCTGATGGGAGTA 
                 SEQ ID 
                 GTGGCGGGAGCTACTTCCCTATGGT 
               
               
                   
                 CTATGCTATGCAC 
                 1079 
                 GCACAAGCTACGCGGACTCCG 
                 1144 
                 AC 
               
               
                   
                   
                   
                 TGAAGGGC 
                   
                   
               
               
                   
               
               
                 SEQ ID 1022 
                 GGAATCAGCTTCAGAGA 
                 SEQ ID 
                 TGGATCAACGCTGGCAATGGT 
                 SEQ ID 
                 CATGGTAGGGCCGGAATAAACTGGT 
               
               
                   
                 TTACTGGATGCAC 
                 1080 
                 AACACAAAATATTCACAGAAG 
                 1145 
                 ACTTCGATCTC 
               
               
                   
                   
                   
                 TTCCAGGGC 
                   
                   
               
               
                   
               
               
                 SEQ ID 1023 
                 GGATACACCTTCACTAG 
                 SEQ ID 
                 CTTATTTATAGTGATGGTCGCA 
                 SEQ ID 
                 GCGCCCCCTCCGACTGTTGGCTGGT 
               
               
                   
                 CTATGCTATGCAT 
                 1081 
                 CAAACTATGCAGACTCCGTGA 
                 1146 
                 ACGCCCCCGTCTTTGACTAC 
               
               
                   
                   
                   
                 AGGGC 
                   
                   
               
               
                   
               
               
                 SEQ ID 1024 
                 GGGTTCACCGTCAGTAG 
                 SEQ ID 
                 AACATAAAGCAAGATGGAACT 
                 SEQ ID 
                 GACTATTACTATGGTTCGGGGAGTT 
               
               
                   
                 CAACTACATGAGC 
                 1082 
                 GAGAAACACTATGTGGACTCT 
                 1147 
                 CTCCC 
               
               
                   
                   
                   
                 GTGAAGGGC 
                   
                   
               
               
                   
               
               
                 SEQ ID 1025 
                 GGATTCACCTTTAGTAAC 
                 SEQ ID 
                 GGTATGAGTGGTAGTGGTTATA 
                 SEQ ID 
                 GATCTGAATCGAGGATATTGTAGTG 
               
               
                   
                 AATTGGATGACC 
                 1083 
                 GTACATACTACGCAGACTCCGT 
                 1148 
                 GTGGTAGCTGCTTTGGCTAC 
               
               
                   
                   
                   
                 GAAGGGC 
                   
                   
               
               
                   
               
               
                 SEQ ID 1026 
                 GAATTCACCCTTAGGAA 
                 SEQ ID 
                 GCTATTAGTAGTAATGGGGGT 
                 SEQ ID 
                 GCCCAGCCGGGCGCTGAGACGTTGA 
               
               
                   
                 CTATGGCGTGAGC 
                 1084 
                 AGCACATACTACGCAGACTCA 
                 1149 
                 ACTTCGATCTC 
               
               
                   
                   
                   
                 GTGAAGGGC 
                   
                   
               
               
                   
               
               
                 SEQ ID 1027 
                 GGTTACACATTTACCAGT 
                 SEQ ID 
                 TGGATCAGCGCTTACGACGGT 
                 SEQ ID 
                 CCGGGTATGGTTCGGGGAGTTATTA 
               
               
                   
                 TATGCCATCAGC 
                 1085 
                 AACACAAACTATGCACAGAAG 
                 1150 
                 CTGCCCCGCTTGACTAC 
               
               
                   
                   
                   
                 CTCCAGGGC 
                   
                   
               
               
                   
               
               
                 SEQ ID 1028 
                 GGATTCACCTTCAGTACC 
                 SEQ ID 
                 GTTATATCATATGATGGACGTA 
                 SEQ ID 
                 GGGGGGACTATGGTTCGGGGTTTCG 
               
               
                   
                 TATCCCATGCAC 
                 1086 
                 ATGAATACTACGCAGACTCCGT 
                 1151 
                 GATTTAACTAC 
               
               
                   
                   
                   
                 GAAGGGC 
                   
                   
               
               
                   
               
               
                 SEQ ID 1029 
                 GGATTCACCTTTGATGAT 
                 SEQ ID 
                 GCTATTAGTGGTAGTGGTGGTA 
                 SEQ ID 
                 GCCACGTATTACTATGATAGTAGTG 
               
               
                   
                 TATGCCATGCAC 
                 1087 
                 GCACATACTACGCAGACTCCGT 
                 1152 
                 GTTATAGGTTTGACTAC 
               
               
                   
                   
                   
                 GAAGGGC 
                   
                   
               
               
                   
               
               
                 SEQ ID 1030 
                 GGGGACAGTGTCTCTAA 
                 SEQ ID 
                 AGGACATACTACAGGTCCAAG 
                 SEQ ID 
                 GAGGCTGCCGACGACCCGTTTGACC 
               
               
                   
                 CAACAGGGCTGCTTGGA 
                 1088 
                 TGGTATAATGAATATGCAGTCT 
                 1153 
                 AT 
               
               
                   
                 AC 
                   
                 CTGTGAAAAGT 
                   
                   
               
               
                   
               
               
                 SEQ ID 1031 
                 GGATTCACCTTCAGTGA 
                 SEQ ID 
                 CGAATTACAAATAAGCGTACC 
                 SEQ ID 
                 GGCCCCGGGGCAGTGGCTGGTACTA 
               
               
                   
                 CCCCTACATGGAC 
                 1089 
                 GGTTACGCCACAACATATGCC 
                 1154 
                 AGCCAAAGTACTACTTTGACTAC 
               
               
                   
                   
                   
                 GCGTCTGTGAAGGAC 
                   
                   
               
               
                   
               
               
                 SEQ ID 1032 
                 GGATTCACTTTCAGTAAC 
                 SEQ ID 
                 CGTATTAAAAGCAAAACTGAT 
                 SEQ ID 
                 GACAAGATCGGCAGCTGTCCTTAC 
               
               
                   
                 GCCTGGATGAGC 
                 1090 
                 GGTGGGACAACAGACTACGCT 
                 1155 
                   
               
               
                   
                   
                   
                 GCACCCGTGAAAGGC 
                   
                   
               
               
                   
               
               
                 SEQ ID 1033 
                 GGGGACAGTGTCTCTAG 
                 SEQ ID 
                 AGGACATACTACAGGTCCAAG 
                 SEQ ID 
                 GGAATCTATGATAGTAGTGGTTCTT 
               
               
                   
                 CAACAGTGCTGCTTGGA 
                 1091 
                 TGGTATAATGATTATGCAGTAT 
                 1156 
                 CCAATCCCTTTGACTCC 
               
               
                   
                 AC 
                   
                 CTGTGAAAAGT 
                   
                   
               
               
                   
               
               
                 SEQ ID 1034 
                 GGATTCACCTTCAGTAG 
                 SEQ ID 
                 TACATCTATCATAGTGGGAGCA 
                 SEQ ID 
                 ACTTTTGCGGGGTATAGCAGCAAAC 
               
               
                   
                 CTATGCTATGCAT 
                 1092 
                 CCTACTACAACCCGTCCCTCAA 
                 1157 
                 TGGGGTACTTCGATCTC 
               
               
                   
                   
                   
                 GAGT 
                   
                   
               
               
                   
               
               
                 SEQ ID 1035 
                 GGTGGCTCCATCAGCAG 
                 SEQ ID 
                 AGGACTTACTACAGGTCCAAG 
                 SEQ ID 
                 GCCCGAGTGGAATCCAAGGATGGGT 
               
               
                   
                 TGGTGGTTACTCCTGGA 
                 1093 
                 TGGTATAATGATTATGCAGTAT 
                 1158 
                 ACTTTGACTAC 
               
               
                   
                 GC 
                   
                 CTCTGAAAAGT 
                   
                   
               
               
                   
               
               
                 SEQ ID 1036 
                 GGGGACAGTGTCTCTGG 
                 SEQ ID 
                 TTCATTAGAGCCAACGCTGATA 
                 SEQ ID 
                 GACCTGCGACTTTCTACGTGGGATG 
               
               
                   
                 CAACAGTGCTGCTTGGA 
                 1094 
                 GTGGGACAACAGAGTACGCCG 
                 1159 
                 CTTATGATTTC 
               
               
                   
                 AC 
                   
                 CGTCTGTGAAAGGC 
                   
                   
               
               
                   
               
               
                 SEQ ID 1037 
                 GGATTCACCTTTGCTGCT 
                 SEQ ID 
                 AGGACATACTACAGGTCCAAG 
                 SEQ ID 
                 GGATCGGTATATAGTGGGAGCTACT 
               
               
                   
                 TATAATATCAAC 
                 1095 
                 TGGTATAATGATTATGCAGTAT 
                 1160 
                 ATATGCTCATTGACTAC 
               
               
                   
                   
                   
                 CTGTGAAGAGT 
                   
                   
               
               
                   
               
               
                 SEQ ID 1038 
                 GGGGACAGTGTCTCTAG 
                 SEQ ID 
                 AGGACATTCTACAGGTCCAAG 
                 SEQ ID 
                 CGGGATTGGGCAGGAAAAAGGGTC 
               
               
                   
                 CAACAATGCTGCTTGGA 
                 1096 
                 TGGTATAATGACTATGCAGTTT 
                 1161 
                   
               
               
                   
                 AC 
                   
                 CTGTGAAAAGT 
                   
                   
               
               
                   
               
               
                 SEQ ID 1039 
                 GGTTACACCTTTACCAGC 
                 SEQ ID 
                 TGGATCATCCCTATCTTTGGTA 
                 SEQ ID 
                 GATGGGGGGTCCAGCCCATACTATG 
               
               
                   
                 TATGGTATCAGC 
                 1097 
                 TAGCAAACTACGCACAGAAGT 
                 1162 
                 ATAGTAGTGGTTTACTACCCTGGTA 
               
               
                   
                   
                   
                 TCCAGGGC 
                   
                 CTTCGATCTC 
               
               
                   
               
               
                 SEQ ID 1040 
                 GGATTCACCTTTAGCAG 
                 SEQ ID 
                 TGGATCAACGCTGGCAATGGT 
                 SEQ ID 
                 GGCAATGGGCCGTTCGACCCC 
               
               
                   
                 CTATGCCATGAGC 
                 1098 
                 AACACAAAATATTCAGAGAAG 
                 1163 
                   
               
               
                   
                   
                   
                 TTCGAAGGC 
                   
                   
               
               
                   
               
               
                 SEQ ID 1041 
                 GGATTCACCTTTAGCAA 
                 SEQ ID 
                 TACATCAGTAGTACTAGTAGTA 
                 SEQ ID 
                 GGACGGACTCACTGGGGCCCCCAGG 
               
               
                   
                 CTATGTCATGAGC 
                 1099 
                 CCATATACTACGCAGACTCCGT 
                 1164 
                 ACTTTGACTAC 
               
               
                   
                   
                   
                 GAAGGGC 
                   
                   
               
               
                   
               
               
                 SEQ ID 1042 
                 GGATTCACCTTCAGCAG 
                 SEQ ID 
                 GCTATTAGTGGTATTGGTGATA 
                 SEQ ID 
                 AGGGGACATAACTACGGTGTAGATT 
               
               
                   
                 CTCTGCCATGCAC 
                 1100 
                 CTACATACTACGCGGACTCCGT 
                 1165 
                 AC 
               
               
                   
                   
                   
                 GAAGGGC 
                   
                   
               
               
                   
               
               
                 SEQ ID 1043 
                 GGAGGCACCTTCAGCAG 
                 SEQ ID 
                 AGGACATATTACAGGTCCAAG 
                 SEQ ID 
                 GATTATTGTAGTAGTACCAGCTGCC 
               
               
                   
                 CTATGCTATCAGC 
                 1101 
                 TGGTATAATGATTATGCAGTAT 
                 1166 
                 AGAACTGGTTCGACCCC 
               
               
                   
                   
                   
                 CTGTGAAAAGT 
                   
                   
               
               
                   
               
               
                 SEQ ID 1044 
                 GGATACAGCTTTACCAG 
                 SEQ ID 
                 ATGATTTGGCATGATGAGAGT 
                 SEQ ID 
                 TGGTACGGTGACTACGGCCTTGACT 
               
               
                   
                 CTACTGGATCGCC 
                 1102 
                 AAGAAATACTATGCAGACTCC 
                 1167 
                 AC 
               
               
                   
                   
                   
                 GTGAAGGGC 
                   
                   
               
               
                   
               
               
                 SEQ ID 1045 
                 CGATTCACTTTCAGTGAC 
                 SEQ ID 
                 GGGATCATCCCTATCTTTGGTA 
                 SEQ ID 
                 GTTACGGGACGGAGAGTGGGAGCC 
               
               
                   
                 GCCTGGATGAGC 
                 1103 
                 CAGCAAACTACGCACAGAAGT 
                 1168 
                 CATGACTAC 
               
               
                   
                   
                   
                 TCCAGGGC 
                   
                   
               
               
                   
               
               
                 SEQ ID 1046 
                 GGATTCACCTTCAGTACC 
                 SEQ ID 
                 GTCATCTATCCTGGTGACTCTG 
                 SEQ ID 
                 GGCTCCTTGTCCCGAAGTGGCTGGT 
               
               
                   
                 TATGGCATGCAC 
                 1104 
                 ATACCAGATACAGCCCGTCCTT 
                 1169 
                 ACGCCGGACTCTTTGACTAC 
               
               
                   
                   
                   
                 CCAAGGC 
                   
                   
               
               
                   
               
               
                 SEQ ID 1047 
                 GGATTCACCGTCAGTAG 
                 SEQ ID 
                 CGTATTAAAAGCAAAATAAGT 
                 SEQ ID 
                 GGGGCCCTACAGGGCGAATGGCGG 
               
               
                   
                 CAACTACATGAGC 
                 1105 
                 GGTGGGACAACAGACTACGCT 
                 1170 
                 AGATTTGACTAC 
               
               
                   
                   
                   
                 GCACCCGTGCAAGGC 
                   
                   
               
               
                   
               
               
                 SEQ ID 1048 
                 GGATTCACCTTCAGTAG 
                 SEQ ID 
                 GCTATTAGTAGTAATGGGGGT 
                 SEQ ID 
                 AACAGTCAACGTTCGTTTGACTAC 
               
               
                   
                 CTATAGCATGAAC 
                 1106 
                 AGCACATATTATGCAAACTCTG 
                 1171 
                   
               
               
                   
                   
                   
                 TGAAGGGC 
                   
                   
               
               
                   
               
               
                 SEQ ID 1049 
                 GGGGACAGTGTCTCTAG 
                 SEQ ID 
                 GGTATTAGTGGTAGTGGTGGTA 
                 SEQ ID 
                 GGGCCCCGAATGTGGAGCAGTGGC 
               
               
                   
                 CGACAGTGCTGTTTGGA 
                 1107 
                 GCACATACTACGCAGACTCCGT 
                 1172 
                 ATTGATGCTTTTGATATC 
               
               
                   
                 CC 
                   
                 GAAGGGC 
                   
                   
               
               
                   
               
               
                 SEQ ID 1050 
                 GGATTCACCTTTGGTGAT 
                 SEQ ID 
                 CTTATATCATATGATGGAAGTA 
                 SEQ ID 
                 CGGGCGGGTTACGGTGACTACAGAC 
               
               
                   
                 TATGCTATGAGC 
                 1108 
                 AAAAATACTATGCAAACTCCG 
                 1173 
                 ACTTCCAGCAC 
               
               
                   
                   
                   
                 TGAAGGGC 
                   
                   
               
               
                   
               
               
                 SEQ ID 1051 
                 GGATTCACCTTCAGTAGT 
                 SEQ ID 
                 GTTATTTATAGCGGTGGTAGCA 
                 SEQ ID 
                 CATAGACGCCCAATTTACGATATTT 
               
               
                   
                 TATAGCATGAAC 
                 1109 
                 CATACTACGCAGACTCCGTGA 
                 1174 
                 TGACTGGTTTTGACTAC 
               
               
                   
                   
                   
                 AGGGC 
                   
                   
               
               
                   
               
               
                 SEQ ID 1052 
                 GGATACACCTTCACTGA 
                 SEQ ID 
                 TACATTAGTAGTAGTGGTAGTT 
                 SEQ ID 
                 GATGGTACGGTCCGAAGGGTAGTGG 
               
               
                   
                 TTATGCTATACAT 
                 1110 
                 ACACAAACTACGCAGACTCTG 
                 1175 
                 GAGCTACTACCCCTGGAAACTTTGA 
               
               
                   
                   
                   
                 TGAAGGGC 
                   
                 CTAC 
               
               
                   
               
               
                 SEQ ID 1053 
                 GGTGGCTCCATCAGTAG 
                 SEQ ID 
                 CGTATTAAAAGCAAAACTGAT 
                 SEQ ID 
                 CGGGATACACCTTTGGTTGGGGTTT 
               
               
                   
                 TTACTACTGGAGC 
                 1111 
                 GGTGAGACAACAGACTACGCT 
                 1176 
                 CGATATAC 
               
               
                   
                   
                   
                 GCACCCGTGAAAGGC 
                   
                   
               
               
                   
               
               
                 SEQ ID 1054 
                 GGATTCACCTTCAGTAG 
                 SEQ ID 
                 AGGACATACTACAAGTCGAAG 
                 SEQ ID 
                 GATAACGATTTTTGGAGTGGGAAAG 
               
               
                   
                 CTATGGCATGCAC 
                 1112 
                 TGGTATAATGATTATGCAGCAT 
                 1177 
                 TCTTTGACTAC 
               
               
                   
                   
                   
                 CTGTGAAAAGT 
                   
                   
               
               
                   
               
               
                 SEQ ID 1055 
                 GGATTCACCTTCAGTGA 
                 SEQ ID 
                 TTCATTAGAAGCAAAGCTTATG 
                 SEQ ID 
                 GGCCGGTCCCTTCCCTACCGGGGGT 
               
               
                   
                 CCAGTACATGGAC 
                 1113 
                 GTGGGACAACAGAATACGCCG 
                 1178 
                 TGGCTCCTAGATCTTTCGGAGGATA 
               
               
                   
                   
                   
                 CGTCTGTGAAAGGC 
                   
                 CTACTTTGACTAC 
               
               
                   
               
               
                 SEQ ID 1056 
                 GGTGGGTCCTTCAGTGG 
                 SEQ ID 
                 TACATTAGTAGTAGTGGTACTA 
                 SEQ ID 
                 TTGCCTAGTAGTGGTTATCTACAGG 
               
               
                   
                 TTACTACTGGAGC 
                 1114 
                 CCATATACTACGCAGACTCTGT 
                 1179 
                 ACCACCACTACTACGGTATGGACGT 
               
               
                   
                   
                   
                 GAAGGGC 
                   
                 C 
               
               
                   
               
               
                 SEQ ID 1057 
                 GGATTCACCTTCAGCAG 
                 SEQ ID 
                 ATTATATCAGATGATGGAAGT 
                 SEQ ID 
                 GATGTCAGTGGGTCCTTCGCGGCCT 
               
               
                   
                 CTATGCTATCAGC 
                 1115 
                 AAGAGTTACTACGCAGACTCC 
                 1180 
                 AC 
               
               
                   
                   
                   
                 GTGCAGGGC 
                   
                   
               
               
                   
               
               
                 SEQ ID 1058 
                 GGATACACCTTCACCAG 
                 SEQ ID 
                 TGGATCAACGCTGGCGATGGT 
                 SEQ ID 
                 GACGAGTATTTCTAC 
               
               
                   
                 CTACTATATGCAC 
                 1116 
                 GGCACAAAAAGTTCACGGGAG 
                 1181 
                   
               
               
                   
                   
                   
                 TTCCAGGGC 
                   
                   
               
               
                   
               
               
                 SEQ ID 1059 
                 GGGGACAGTGTCTCTAG 
                 SEQ ID 
                 TATATCTATTACACTGGGAGCA 
                 SEQ ID 
                 GAGGCTAGCAGTGGCTGGAAC 
               
               
                   
                 CAAAAGTGCTGCTTGGA 
                 1117 
                 CCAACTACAACCCCTCCCTCAA 
                 1182 
                   
               
               
                   
                 AC 
                   
                 GAGC 
                   
                   
               
               
                   
               
               
                 SEQ ID 1060 
                 GGATACAGCTTTACCAG 
                 SEQ ID 
                 GTTATATCATATGATGGAAGTA 
                 SEQ ID 
                 GAGGGCGGAGCAGTGGCTGGTACT 
               
               
                   
                 CTACTGGATCGGC 
                 1118 
                 ATAAATACTATGCAGACTCCGT 
                 1183 
                 GTCTAC 
               
               
                   
                   
                   
                 GAAGGGC 
                   
                   
               
               
                   
               
               
                 SEQ ID 1061 
                 GGATACACCCTCACTGA 
                 SEQ ID 
                 CGTGTTAGAAACAAAGCTAAC 
                 SEQ ID 
                 GATCGGCGTTACTATGATAGTAGTG 
               
               
                   
                 ATTATCCATGCAC 
                 1119 
                 AGTTACACCACAGAATACGCC 
                 1184 
                 GTTATTATCCCGCCTACTACTTTGAC 
               
               
                   
                   
                   
                 GCGTCTGTGAAAGGC 
                   
                 TAC 
               
               
                   
               
               
                   
                   
                 SEQ ID 
                 GAAATCAATCATAGTGGAAGC 
                 SEQ ID 
                 GGCGGTACTTGGGATACAGCTATGG 
               
               
                   
                   
                 1120 
                 ACCAACTACAACCCGTCCCTCA 
                 1185 
                 TTACGGGCTTTGACTAC 
               
               
                   
                   
                   
                 AGAGT 
                   
                   
               
               
                   
               
               
                   
                   
                 SEQ ID 
                 GGGATCATCCCTATGTATGGTA 
                 SEQ ID 
                 ATAGTGGGAGGTGCCGTTGACTGC 
               
               
                   
                   
                 1121 
                 CAGCAAACTACGCACAGAAGT 
                 1186 
                   
               
               
                   
                   
                   
                 TCCAGGGC 
                   
                   
               
               
                   
               
               
                   
                   
                 SEQ ID 
                 ATAATCAACCCTAGTGGTGGTA 
                 SEQ ID 
                 GAGGATACTATGGTTCGGGGAGTTA 
               
               
                   
                   
                 1122 
                 GCACAAGCTACGCACAGAAGT 
                 1187 
                 TTCCC 
               
               
                   
                   
                   
                 TCCAGGGC 
                   
                   
               
               
                   
               
               
                   
                   
                 SEQ ID 
                 AGGACATACTACAGGTCCAAA 
                 SEQ ID 
                 TTGGCGAGTGGTTCCCCCCCTCCGG 
               
               
                   
                   
                 1123 
                 TGGAATAATGATTATGCATTAT 
                 1188 
                 GGGACTAC 
               
               
                   
                   
                   
                 CTGTGAAAAGT 
                   
                   
               
               
                   
               
               
                   
                   
                 SEQ ID 
                 ATCATCTATCCTGGTGACTCTG 
                 SEQ ID 
                 GTTAGAGTGGGAGCTACTACTGTTT 
               
               
                   
                   
                 1124 
                 ATACCAGATACAGCCCGTCCTT 
                 1189 
                 ACGACAGCTGGTTCGACCCC 
               
               
                   
                   
                   
                 CCAAGGC 
                   
                   
               
               
                   
               
               
                   
                   
                 SEQ ID 
                 TTTATATCATATGATGGAAGTA 
                 SEQ ID 
                 GATGATCGGGGTCGGGGAGATGACT 
               
               
                   
                   
                 1125 
                 ATAAATACTACGCAGACTCCGT 
                 1190 
                 TTGACTAC 
               
               
                   
                   
                   
                 GAAGGGC 
                   
                   
               
               
                   
               
               
                   
                   
                 SEQ ID 
                 GGTTTTGATCCTGAAGATGGTG 
                 SEQ ID 
                 CTAGCTAATTCCGACGGTGTGGACG 
               
               
                   
                   
                 1126 
                 AAACAATCTACGCACAGAAGT 
                 1191 
                 TC 
               
               
                   
                   
                   
                 TCCAGGGC 
                   
                   
               
               
                   
               
               
                   
                   
                   
                   
                 SEQ ID 
                 GGCGGTGGTTCGGGGAGTTATTATA 
               
               
                   
                   
                   
                   
                 1192 
                 AGAGGTTCTTTGACTAC 
               
               
                   
               
               
                   
                   
                   
                   
                 SEQ ID 
                 GGGGGAAGATATACCAAGGGAGGG 
               
               
                   
                   
                   
                   
                 1193 
                 TACTTTGACGAC 
               
               
                   
               
               
                   
                   
                   
                   
                 SEQ ID 
                 GAACTATACAACTATGGTTCAAAGG 
               
               
                   
                   
                   
                   
                 1194 
                 ACTACTTTGACTAC 
               
               
                   
               
               
                   
                   
                   
                   
                 SEQ ID 
                 GATGGCCCCGCCGTTGATGGTGCTG 
               
               
                   
                   
                   
                   
                 1195 
                 AATACTTCCAGCAC 
               
               
                   
               
               
                   
                   
                   
                   
                 SEQ ID 
                 GTCGCCAAATATTATTACGAGAGTG 
               
               
                   
                   
                   
                   
                 1196 
                 GTGGTTATCGGGCCTCCAACTGGTT 
               
               
                   
                   
                   
                   
                   
                 CGACCCC 
               
               
                   
               
               
                   
                   
                   
                   
                 SEQ ID 
                 GAAGGGGGCAGTGGCTGGCGCCAC 
               
               
                   
                   
                   
                   
                 1197 
                 TACTTTGACTAC 
               
               
                   
               
               
                   
                   
                   
                   
                 SEQ ID 
                 GATCAAGGGGCAGCAGCTGGTACCC 
               
               
                   
                   
                   
                   
                 1198 
                 TGGGGTACTTTGACTAC 
               
               
                   
               
               
                   
                   
                   
                   
                 SEQ ID 
                 GGGCGCGTGGCGGGGGATGCTTTTG 
               
               
                   
                   
                   
                   
                 1199 
                 ATATC 
               
               
                   
               
               
                   
                   
                   
                   
                 SEQ ID 
                 ACCAACCAGGGATACGGTGGTAACT 
               
               
                   
                   
                   
                   
                 1200 
                 CCGGGGTATTTGACTAC 
               
               
                   
               
               
                   
                   
                   
                   
                 SEQ ID 
                 CCCCCCGACGGTGGTAACTCCGGTC 
               
               
                   
                   
                   
                   
                 1201 
                 GCTGGTACTTCGATCTC 
               
               
                   
               
               
                   
                   
                   
                   
                 SEQ ID 
                 GCCCGGGGGCTACAGTACCTAATCT 
               
               
                   
                   
                   
                   
                 1202 
                 GGTACTTCGATCTC 
               
               
                   
               
               
                   
                   
                   
                   
                 SEQ ID 
                 GCTCGTTACTATGATAGTAGTGGTT 
               
               
                   
                   
                   
                   
                 1203 
                 ATATTGCCCCATCGGGTTACTTTGA 
               
               
                   
                   
                   
                   
                   
                 CTAC 
               
               
                   
               
               
                   
                   
                   
                   
                 SEQ ID 
                 GATGGTGTAGGAGGGAGAGATGGC 
               
               
                   
                   
                   
                   
                 1204 
                 TACAATTTTGACTAC 
               
               
                   
               
               
                   
                   
                   
                   
                 SEQ ID 
                 CCCCATTACGATATTTTGACTGGTTC 
               
               
                   
                   
                   
                   
                 1205 
                 CCGGGCGCCCTTTGACTAC 
               
               
                   
               
               
                   
                   
                   
                   
                 SEQ ID 
                 CGAAACTTAGGCTAC 
               
               
                   
                   
                   
                   
                 1206 
                   
               
               
                   
               
               
                   
                   
                   
                   
                 SEQ ID 
                 GCTAAGTTTTGGACATACTACTTTG 
               
               
                   
                   
                   
                   
                 1207 
                 ACTAC 
               
               
                   
               
               
                   
                   
                   
                   
                 SEQ ID 
                 AAAATAGCAGCAGCTGGTAAGCAA 
               
               
                   
                   
                   
                   
                 1208 
                 CCTGTTGACTAC 
               
               
                   
               
               
                   
                   
                   
                   
                 SEQ ID 
                 GGCCCTATAGTGGGAGCGACTATGG 
               
               
                   
                   
                   
                   
                 1209 
                 ACTAC 
               
               
                   
               
               
                   
                   
                   
                   
                 SEQ ID 
                 AGACCGGATAGCAGCAGTCAATGTT 
               
               
                   
                   
                   
                   
                 1210 
                 TTGACTAC 
               
               
                   
               
               
                   
                   
                   
                   
                 SEQ ID 
                 GCCCCCCTAGCAGCAGATGGCTACT 
               
               
                   
                   
                   
                   
                 1211 
                 TTGACTAC 
               
               
                   
               
               
                   
                   
                   
                   
                 SEQ ID 
                 GACGGGGGCTATGATAGTAGTGGTT 
               
               
                   
                   
                   
                   
                 1212 
                 TTCACTTTGACTAC 
               
               
                   
               
               
                   
                   
                   
                   
                 SEQ ID 
                 GGGGTGGGATGGTCGCCCTTCCAAT 
               
               
                   
                   
                   
                   
                 1213 
                 AC 
               
               
                   
               
               
                   
                   
                   
                   
                 SEQ ID 
                 GGTGTAACCCGGACCTTTGACTAC 
               
               
                   
                   
                   
                   
                 1214 
                   
               
               
                   
               
               
                   
                   
                   
                   
                 SEQ ID 
                 GACGACAAAATAGCAGCAGCTGGA 
               
               
                   
                   
                   
                   
                 1215 
                 TTCACATACTGGTACTTCGATCTC 
               
               
                   
               
               
                   
                   
                   
                   
                 SEQ ID 
                 GATTATAGCAGCTCGGGGGAGTGCT 
               
               
                   
                   
                   
                   
                 1216 
                 TTGACTAC 
               
               
                   
               
               
                   
                   
                   
                   
                 SEQ ID 
                 TTAAGGGGTATAGATTACTATGATA 
               
               
                   
                   
                   
                   
                 1217 
                 GTAGTGGTTACCAACGGGGGTTTGA 
               
               
                   
                   
                   
                   
                   
                 CTAC 
               
               
                   
               
               
                   
                   
                   
                   
                 SEQ ID 
                 GCGCCGAGGGGTGTAGTACCAGCTG 
               
               
                   
                   
                   
                   
                 1218 
                 CTATGCGGGGGGGCTAC 
               
               
                   
               
               
                   
                   
                   
                   
                 SEQ ID 
                 GACAGGGGAACTAAATGGAACCAA 
               
               
                   
                   
                   
                   
                 1219 
                 TTGAATGATGTTTTTGATATG 
               
               
                   
               
               
                   
                   
                   
                   
                 SEQ ID 
                 GGATATTGTAGTGGTGGTAGCTGCC 
               
               
                   
                   
                   
                   
                 1220 
                 CAGGAACGGATTTTGACTAC 
               
               
                   
               
               
                   
                   
                   
                   
                 SEQ ID 
                 GGTGGGAGGGGGGATGGGGCCGCT 
               
               
                   
                   
                   
                   
                 1221 
                 TTTGACATC 
               
               
                   
               
               
                   
                   
                   
                   
                 SEQ ID 
                 GATTTAGGGGATCCCCGGGGTGGTA 
               
               
                   
                   
                   
                   
                 1222 
                 TTTTGAACTAC 
               
               
                   
               
               
                   
                   
                   
                   
                 SEQ ID 
                 AGTCTCAATAGTGGGGGCTACCGAT 
               
               
                   
                   
                   
                   
                 1223 
                 GCTTCCATCAC 
               
               
                   
               
               
                   
                   
                   
                   
                 SEQ ID 
                 GTAAATCCGGGGAGTTATACGAGGG 
               
               
                   
                   
                   
                   
                 1224 
                 AGGTGAGCAACTTTGACTAC 
               
               
                   
               
               
                   
                   
                   
                   
                 SEQ ID 
                 CTCCCGGGGAGAGCAGCTCGTCCAG 
               
               
                   
                   
                   
                   
                 1225 
                 ACTAC 
               
               
                   
               
               
                   
                   
                   
                   
                 SEQ ID 
                 GAAGCTAAGTGGGGAATGTACTACT 
               
               
                   
                   
                   
                   
                 1226 
                 TTGACTAC 
               
               
                   
               
               
                   
                   
                   
                   
                 SEQ ID 
                 GGCCGAGGGTATAGCAGCAGTCGG 
               
               
                   
                   
                   
                   
                 1227 
                 CTCTACTACTTTGACTAC 
               
               
                   
               
               
                   
                   
                   
                   
                 SEQ ID 
                 TTGGTGGGCAATAGTGGGAGCTACT 
               
               
                   
                   
                   
                   
                 1228 
                 ATCCGTTTGGGTAC 
               
               
                   
               
               
                   
                   
                   
                   
                 SEQ ID 
                 CAAGTCGCGGGCGGTATGGACGTC 
               
               
                   
                   
                   
                   
                 1229 
                   
               
               
                   
               
               
                   
                   
                   
                   
                 SEQ ID 
                 GGGGGAGGGCTTTGGGCTTTTGATA 
               
               
                   
                   
                   
                   
                 1230 
                 TC 
               
               
                   
               
               
                   
                   
                   
                   
                 SEQ ID 
                 CTCCCCTCGTATTACTATGATAGTA 
               
               
                   
                   
                   
                   
                 1231 
                 GTGGTTACTTTACCTGGTACTTCGAT 
               
               
                   
                   
                   
                   
                   
                 CTC 
               
               
                   
               
               
                   
                   
                   
                   
                 SEQ ID 
                 ACAGGGGACCGCTTCCAAGAGTTTG 
               
               
                   
                   
                   
                   
                 1232 
                 ACTAC 
               
               
                   
               
               
                   
                   
                   
                   
                 SEQ ID 
                 GATGTGAACCCGGAGCTACTGGGGG 
               
               
                   
                   
                   
                   
                 1233 
                 CGGGATTTGACTAC 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 8 
               
             
            
               
                   
               
               
                 Light Chain CDR DNA Sequences 
               
            
           
           
               
               
               
               
               
               
            
               
                 SEQ ID 
                 CDRL1 DNA Seq 
                 SEQ ID 
                 CDRL2 DNA Seq 
                 SEQ ID 
                 CDRL3DNASeq 
               
               
                   
               
               
                 SEQ ID 
                 GCCAGTCAGAGTGTCGGTAACTCCTTA 
                 SEQ ID 1308 
                 GGTGCGTCCAGTTTGCAG 
                 SEQ ID 
                 CAACGTGGCACCTGGCCT 
               
               
                 1234 
                 GCCTGG 
                   
                 AGTGGG 
                 1373 
                 CCCCTCACTTTC 
               
               
                   
               
               
                 SEQ ID 
                 GCCAGTCAGAGTATAACTAACTGGTTG 
                 SEQ ID 1309 
                 AGGGCGTCTCGTTTAGAA 
                 SEQ ID 
                 CAGTATACTAATTACCCTC 
               
               
                 1235 
                 GCCTGG 
                   
                 AGTGGG 
                 1374 
                 GTACGTTC 
               
               
                   
               
               
                 SEQ ID 
                 GCCAGTCAGACTATTAATAGTTGGTTG 
                 SEQ ID 1310 
                 GGTGCTTCCACCAGGGCC 
                 SEQ ID 
                 CAAAGTATACAGCTTCCG 
               
               
                 1236 
                 GCCTGG 
                   
                 ACTGGC 
                 1375 
                 TGGACGTTC 
               
               
                   
               
               
                 SEQ ID 
                 GCAAGTCAGGGCATTAGAAATGATTTA 
                 SEQ ID 1311 
                 GGTGCATCCAGTTTGCAA 
                 SEQ ID 
                 CAATATAATAGTTATTCTC 
               
               
                 1237 
                 GGCTGG 
                   
                 AGTGGA 
                 1376 
                 CCACTTTT 
               
               
                   
               
               
                 SEQ ID 
                 GCAAGTCAGAGCATTAGCAGCTATTTA 
                 SEQ ID 1312 
                 GCTGCATCCAGTTTGCAC 
                 SEQ ID 
                 CACTATGGTCCCTCACGTC 
               
               
                 1238 
                 AATTGG 
                   
                 ACTGGG 
                 1377 
                 GGATCACCTTC 
               
               
                   
               
               
                 SEQ ID 
                 TCCAGCCAGAGTGTTTTATACAGCTCC 
                 SEQ ID 1313 
                 GCTGCATCCACTTTGCAA 
                 SEQ ID 
                 CAGCATAATTCCTACCCTC 
               
               
                 1239 
                 AACAATAAGAACTACATAGCTTGG 
                   
                 AGTGGG 
                 1378 
                 GAACATTC 
               
               
                   
               
               
                 SEQ ID 
                 GCCAGTCAGGGCATTAGCAGTTCTTTG 
                 SEQ ID 1314 
                 GCTGCATCCACCAGGGCC 
                 SEQ ID 
                 CAGAGTTACAGTATTCCTC 
               
               
                 1240 
                 GCCTGG 
                   
                 ACTGGT 
                 1379 
                 GAACGTTC 
               
               
                   
               
               
                 SEQ ID 
                 GCCAGTGAGAGTGTTAATAGCAACTTC 
                 SEQ ID 1315 
                 GGTGCCTCCAGCAGGGCC 
                 SEQ ID 
                 CAATATTATTATATTCCTC 
               
               
                 1241 
                 TTAGCCTGG 
                   
                 GCTGGC 
                 1380 
                 GGACGTTC 
               
               
                   
               
               
                 SEQ ID 
                 GCCAGTCAGAGTGTTGGCAGCAAATTA 
                 SEQ ID 1316 
                 GCTGCATCCTACAGGGCC 
                 SEQ ID 
                 CAGTATGGTAGCTCATCC 
               
               
                 1242 
                 GCCTGG 
                   
                 ACTGGC 
                 1381 
                 ATGTACACTTTT 
               
               
                   
               
               
                 SEQ ID 
                 GCCAGTCAGAATGTTTACAGCAATTTC 
                 SEQ ID 1317 
                 AAGGTTTCTAACCGGTTG 
                 SEQ ID 
                 CAGTATGATAATCTCCCTC 
               
               
                 1243 
                 TTAGCCTGG 
                   
                 TCTGGG 
                 1382 
                 CTCTCACTTTC 
               
               
                   
               
               
                 SEQ ID 
                 TCTAGTCAAAGTCTCGAACACGGTGAT 
                 SEQ ID 1318 
                 GATGCATCCACCAGGGCC 
                 SEQ ID 
                 CAGTATAATAACTGGCCG 
               
               
                 1244 
                 GGAAACACGTACTTGAGTTGG 
                   
                 ACTGGT 
                 1383 
                 CTCACTTTC 
               
               
                   
               
               
                 SEQ ID 
                 TCTAGTCAGAGCCTCCTGCATAGTAAT 
                 SEQ ID 1319 
                 GGTACATCCACCAGGGCC 
                 SEQ ID 
                 CAGTATAATAGTTATTCGG 
               
               
                 1245 
                 GGAAACAACTATTTGGATTGG 
                   
                 ACTGGT 
                 1384 
                 GGACGTTC 
               
               
                   
               
               
                 SEQ ID 
                 GCCAGTCAGAGTATTAGCAACAACTTA 
                 SEQ ID 1320 
                 GGTGCATCCAGGAGGGC 
                 SEQ ID 
                 CAGTATAATAACTGGCCC 
               
               
                 1246 
                 GCCTGG 
                   
                 CACTGGC 
                 1385 
                 CCGATCACCTTC 
               
               
                   
               
               
                 SEQ ID 
                 GCCAGTCAGAGTGTTAGCAGCACCTCC 
                 SEQ ID 1321 
                 AAGATTTCTAACCGGTTC 
                 SEQ ID 
                 CAATATGGAACCTCACCG 
               
               
                 1247 
                 TTAGCCTGG 
                   
                 TCTGGG 
                 1386 
                 ATCACCTTC 
               
               
                   
               
               
                 SEQ ID 
                 TCTAGTCAAAGCCTCGTATACAGTGAT 
                 SEQ ID 1322 
                 GATGCATCCACCAGGGCC 
                 SEQ ID 
                 CAGTATAATAACTGGCCT 
               
               
                 1248 
                 GGAAACACCTACTTGAGTTGG 
                   
                 ACGGGA 
                 1387 
                 CCCATCACCTTC 
               
               
                   
               
               
                 SEQ ID 
                 TCTAATCAAAGCCTCGTATACAGTGAT 
                 SEQ ID 1323 
                 AAGGTTTCTAAGCGGGAC 
                 SEQ ID 
                 CAAGGTATATACTGGCCT 
               
               
                 1249 
                 GGAGGCACCTACTTGAATTGG 
                   
                 TCTGGG 
                 1388 
                 CGAACCTTC 
               
               
                   
               
               
                 SEQ ID 
                 TCCAGCCAGAGTGTTTTATACAGAACC 
                 SEQ ID 1324 
                 GACTCCAACAGGGCCACT 
                 SEQ ID 
                 CAGCGTAGCAACTGGTCG 
               
               
                 1250 
                 AACAATAAGAACTACTTGGCTTGG 
                   
                 GGC 
                 1389 
                 CTCACTTTC 
               
               
                   
               
               
                 SEQ ID 
                 GCCAGTCAGAGCATTGGGAGCAATTTA 
                 SEQ ID 1325 
                 GAAGTTTCCAACCGGTTC 
                 SEQ ID 
                 CAAGGTCTACAAATCCCT 
               
               
                 1251 
                 GCCTGG 
                   
                 TCTGGA 
                 1390 
                 ATCACTTTC 
               
               
                   
               
               
                 SEQ ID 
                 TCTAGTCAAAGCCTCGTGTACAGTGAT 
                 SEQ ID 1326 
                 GGTGCCTCCACCAGGGCC 
                 SEQ ID 
                 CACTATAATAACTGGCCTC 
               
               
                 1252 
                 GGAAACACCTACTTGTATTGG 
                   
                 ACTGCT 
                 1391 
                 ATACCTTC 
               
               
                   
               
               
                 SEQ ID 
                 GCCAGTCAGAGTGTTAGAGACAACGTA 
                 SEQ ID 1327 
                 GCTGCCTCCACCAGGGCC 
                 SEQ ID 
                 CAGTATGGTAGCTCGTTC 
               
               
                 1253 
                 GGTTGG 
                   
                 ACTGGT 
                 1392 
                   
               
               
                   
               
               
                 SEQ ID 
                 GCCAGTCAGACTATTGGTCCCAAGTCC 
                 SEQ ID 1328 
                 TTGGGTTCTAATCGGGCC 
                 SEQ ID 
                 CAGTATAATTTCTGGCCTT 
               
               
                 1254 
                 TTCGGCTGG 
                   
                 TCCGGG 
                 1393 
                 CGATCACCTTC 
               
               
                   
               
               
                 SEQ ID 
                 TCTAGTCAGAGCCTCCTGCATAGTGAT 
                 SEQ ID 1329 
                 GGTGCATCCTACAGGGCC 
                 SEQ ID 
                 CACTATGGTAGTTCACCTC 
               
               
                 1255 
                 GGAAAGACCTATTTGTATTGG 
                   
                 ACTGGC 
                 1394 
                 CAATCACCTTC 
               
               
                   
               
               
                 SEQ ID 
                 GCCAGTCAGAGTGTTAGTAGCAGCTTA 
                 SEQ ID 1330 
                 AGTGCAACCTCTAGGGCC 
                 SEQ ID 
                 CAAGGTACACAATTTCCTC 
               
               
                 1256 
                 GCCTGG 
                   
                 ACTGGA 
                 1395 
                 AAACGTTC 
               
               
                   
               
               
                 SEQ ID 
                 GCCAGTGAAGGTCTTACCACCAACTTA 
                 SEQ ID 1331 
                 AAGGTTTCTACCCGGTTC 
                 SEQ ID 
                 CAAGGGACACACTGGCCG 
               
               
                 1257 
                 GCCTGG 
                   
                 TCTGGG 
                 1396 
                 TACACTTTT 
               
               
                   
               
               
                 SEQ ID 
                 GCCAGTCAGAGTGTTAGCACCCTCTTA 
                 SEQ ID 1332 
                 GCTGCATCCAGTTTGCAA 
                 SEQ ID 
                 CAATATTACAATCTTCCTC 
               
               
                 1258 
                 GCCTGG 
                   
                 AGTGGG 
                 1397 
                 GATCTTTT 
               
               
                   
               
               
                 SEQ ID 
                 GCCAGTCAGAGTGTTTTCAACAACTAC 
                 SEQ ID 1333 
                 GCTGCCTCCAATCTGCAC 
                 SEQ ID 
                 CAGCATGGTGAATGGCCC 
               
               
                 1259 
                 TTAGCCTGG 
                   
                 AGTGGC 
                 1398 
                 ACCTTC 
               
               
                   
               
               
                 SEQ ID 
                 TCTAGTCAAAGCCTCGTATACAGTGAT 
                 SEQ ID 1334 
                 GATGTATCCACCAGGGCC 
                 SEQ ID 
                 CAAGGTAGACACTGGCCG 
               
               
                 1260 
                 GGAAACACCTACTTGAATTGG 
                   
                 ACTGAT 
                 1399 
                 TACACTCTT 
               
               
                   
               
               
                 SEQ ID 
                 TCTAGTCAGAGCCTCCTACATAGTAGT 
                 SEQ ID 1335 
                 AAGGCGTCTACTATAAAA 
                 SEQ ID 
                 CAGTTTAATAATTGGCCTT 
               
               
                 1261 
                 GGATACAACTATTTGGATTGG 
                   
                 AGTGGG 
                 1400 
                 ACACTTTT 
               
               
                   
               
               
                 SEQ ID 
                 TCTAGTCAGAGCCTCCTGAATAGTAAT 
                 SEQ ID 1336 
                 GCTGCGTCCAATTTGCAA 
                 SEQ ID 
                 CAGCGTAGCAGGTGGCCT 
               
               
                 1262 
                 GGATACAACTATTTGGAGTGG 
                   
                 AGTGGG 
                 1401 
                 CTCACTTTC 
               
               
                   
               
               
                 SEQ ID 
                 GCCAGTCAGAGTGTTACCAGCAACTAC 
                 SEQ ID 1337 
                 TGGGCATCTACCCGGGAA 
                 SEQ ID 
                 CAAAGTATACAGCTTCCG 
               
               
                 1263 
                 TTAGCCTGG 
                   
                 TCCGGG 
                 1402 
                 CTCACTTTC 
               
               
                   
               
               
                 SEQ ID 
                 GCCAGTCAGAGTGTTAGCAGCAGCTCC 
                 SEQ ID 1338 
                 GGTGCATCCACCAGGGCC 
                 SEQ ID 
                 CAGTATGGTAGCTCACCC 
               
               
                 1264 
                 TTAGCCTGG 
                   
                 ACTGGC 
                 1403 
                 CCGGGCACTTTC 
               
               
                   
               
               
                 SEQ ID 
                 GCCAGTCAGAGTATTGGCAGCAACTTA 
                 SEQ ID 1339 
                 AAGGCGTCTACTTTAGCA 
                 SEQ ID 
                 CGCTATGATAACTGGCCTC 
               
               
                 1265 
                 GTCTGG 
                   
                 AATGGG 
                 1404 
                 CCCTTTTT 
               
               
                   
               
               
                 SEQ ID 
                 TCTAGTCAAAGCCTCGAACACACTGAT 
                 SEQ ID 1340 
                 GGTGCATCCACCAGGGCC 
                 SEQ ID 
                 CAGTATAATCACTGGCCTC 
               
               
                 1266 
                 GGAAACACCTACTTAAGTTGG 
                   
                 AGTGGC 
                 1405 
                 TCTACACTTTT 
               
               
                   
               
               
                 SEQ ID 
                 GCAAGTCAGAGCATTAGCAACTATTTA 
                 SEQ ID 1341 
                 GATTCATCCAGCAGGGCC 
                 SEQ ID 
                 CAGGGTAGCAACTGGCCG 
               
               
                 1267 
                 AATTGG 
                   
                 ACTGGC 
                 1406 
                 CTCACTTTC 
               
               
                   
               
               
                 SEQ ID 
                 CCAAGTCAGGACATAGGCACTTATTTA 
                 SEQ ID 1342 
                 GGTGCATCCAACAGGGCC 
                 SEQ ID 
                 CAAGGTACACACTGGCCT 
               
               
                 1268 
                 AATTGG 
                   
                 ACTGGT 
                 1407 
                 CGAACGTTC 
               
               
                   
               
               
                 SEQ ID 
                 GCCAGTCAAAGTGTTAACAGCAACGTA 
                 SEQ ID 1343 
                 GATGCATCCAGCAGGGCC 
                 SEQ ID 
                 CACCGTTACGTGTGGCCGT 
               
               
                 1269 
                 GCCTGG 
                   
                 ACTGGC 
                 1408 
                 TCACTTTC 
               
               
                   
               
               
                 SEQ ID 
                 GCCAGTCAGAGTGTTGGTACCAATTTA 
                 SEQ ID 1344 
                 GATTCATCGAATAGGGCC 
                 SEQ ID 
                 CAGTATGGTAGTTCACCG 
               
               
                 1270 
                 GCCTGG 
                   
                 ACTGGC 
                 1409 
                 ATCACCTTC 
               
               
                   
               
               
                 SEQ ID 
                 GCCAGTCAGAGTATTAGTAGGTGGTTG 
                 SEQ ID 1345 
                 GGTGCATCCAGCAGGGCC 
                 SEQ ID 
                 CAAGGTACACATTGGCCT 
               
               
                 1271 
                 GCCTGG 
                   
                 TCTGGC 
                 1410 
                 CGGACTTTC 
               
               
                   
               
               
                 SEQ ID 
                 GCGAGTCAGAACATTCGCCACTGGTTA 
                 SEQ ID 1346 
                 TGGGCGTCTACCCGGGGG 
                 SEQ ID 
                 CAAGGTCTACAAATTCCG 
               
               
                 1272 
                 GTCTGG 
                   
                 TCCGGG 
                 1411 
                 CTCACTTTC 
               
               
                   
               
               
                 SEQ ID 
                 TCCAGCCGGAATATTTTATACAGCGGC 
                 SEQ ID 1347 
                 AAGGTTTCTAACCGGGAC 
                 SEQ ID 
                 CAGTCTCTACAAACTCCTC 
               
               
                 1273 
                 AACAATAAAAACTTCTTGGCTTGG 
                   
                 TCTGGG 
                 1412 
                 TCACTTTC 
               
               
                   
               
               
                 SEQ ID 
                 GCCAGTCAGAGTATTAGCAGCACCTAC 
                 SEQ ID 1348 
                 GGTGCATCCAGCAGGGCC 
                 SEQ ID 
                 CAGTATGCTAGCTCAGTC 
               
               
                 1274 
                 TTAGCCTGG 
                   
                 ACTGAC 
                 1413 
                 ACCTTC 
               
               
                   
               
               
                 SEQ ID 
                 GCCAGGCAGAGCATCAGTAACCGGTTG 
                 SEQ ID 1349 
                 TATGCTTCCCAGTCCTTCT 
                 SEQ ID 
                 CAGTATAATAACTGGCCT 
               
               
                 1275 
                 GCCTGG 
                   
                 CAGGG 
                 1414 
                 CCCTTCACCTTC 
               
               
                   
               
               
                 SEQ ID 
                 GCCAGTGAGAGTGTTAGCAAGAGCTAC 
                 SEQ ID 1350 
                 TGGGCATCTGCCCGGGAA 
                 SEQ ID 
                 CAGTATGGTAGCTCACAG 
               
               
                 1276 
                 TTACTCTGG 
                   
                 TCCGGG 
                 1415 
                 ACCTTC 
               
               
                   
               
               
                 SEQ ID 
                 GCCAGTCAGAGTGTTAGCAGCAGCGCC 
                 SEQ ID 1351 
                 GGTGCCTCCACCAGGGCC 
                 SEQ ID 
                 CAGTATGGTAGTTCACCTC 
               
               
                 1277 
                 TTAGCCTGG 
                   
                 ACTGGT 
                 1416 
                 CGACCACCTTC 
               
               
                   
               
               
                 SEQ ID 
                 GCCAGTCAAAGTGTTACCAGCAACTTA 
                 SEQ ID 1352 
                 GAGGTTTCTAAGCGGGAC 
                 SEQ ID 
                 CAGCGTAGCAACTGGCCG 
               
               
                 1278 
                 GCCTGG 
                   
                 TCTGGG 
                 1417 
                 TGGACGTTC 
               
               
                   
               
               
                 SEQ ID 
                 GCCAGTCAGAGTATTGGCACTTACGTC 
                 SEQ ID 1353 
                 GAAGTTTCCAACCGATTC 
                 SEQ ID 
                 CAGGCTACACACTATCCTC 
               
               
                 1279 
                 GCCTGG 
                   
                 TCTGGA 
                 1418 
                 GGACGTTC 
               
               
                   
               
               
                 SEQ ID 
                 GCCAGTCAGAGTGTTAGCAGCAACTCC 
                 SEQ ID 1354 
                 GCTTCATCTACTTTGCAA 
                 SEQ ID 
                 CAGAGTTACATTACCCCGT 
               
               
                 1280 
                 TTAGCCTGG 
                   
                 TCAGGG 
                 1419 
                 GGACGTTC 
               
               
                   
               
               
                 SEQ ID 
                 TCCAGCCAGAGTGTTTTATATGATTCC 
                 SEQ ID 1355 
                 AAGGCCTCTAGTTTAACA 
                 SEQ ID 
                 CAGAGTTACGGTCCTCGG 
               
               
                 1281 
                 AACAGTAAGAACTACTTAAGTTGG 
                   
                 AGTGGG 
                 1420 
                 ACATTC 
               
               
                   
               
               
                 SEQ ID 
                 GCCAGTCAGAGTGTTAGTAGCTACTTA 
                 SEQ ID 1356 
                 AAGGCGTCTAGTTTAGAA 
                 SEQ ID 
                 CAGTGTGCTAGCTCACCTC 
               
               
                 1282 
                 GCCTGG 
                   
                 AGTGGG 
                 1421 
                 CTGTCACTTTC 
               
               
                   
               
               
                 SEQ ID 
                 TCTTGTCAAAGCCTCGTATACAGTGAT 
                 SEQ ID 1357 
                 TTGGGTTCTACTCGGGCC 
                 SEQ ID 
                 CAGTATAATAACTGGCCT 
               
               
                 1283 
                 GGCAACACCTACTTGAATTGC 
                   
                 TCCGGG 
                 1422 
                 CCGATAACTTTC 
               
               
                   
               
               
                 SEQ ID 
                 GCCAGTCAGAGTGTTAGCAGCAGCTAC 
                 SEQ ID 1358 
                 GGTGTTTCCACCAGGGCC 
                 SEQ ID 
                 CACTATAAAAGTGATTCC 
               
               
                 1284 
                 TTAGGCTGG 
                   
                 ACTGGC 
                 1423 
                 CGGACGTTC 
               
               
                   
               
               
                 SEQ ID 
                 GCCAGTCAGAGCATTGGTGGTAGCTTA 
                 SEQ ID 1359 
                 ACTGCATCCAAAAGGGCC 
                 SEQ ID 
                 CAGCATAACAGTTACCCG 
               
               
                 1285 
                 CACTGG 
                   
                 ACTGGC 
                 1424 
                 TGGACGTTC 
               
               
                   
               
               
                 SEQ ID 
                 TCCAGCCAGAGTGTTTTATACAGCTCC 
                 SEQ ID 1360 
                 ATGGGTTCTAGTCGGGCC 
                 SEQ ID 
                 CAATATTATAGTACTCCGC 
               
               
                 1286 
                 AACAATAAGAACTACTTAGCTTGG 
                   
                 TCCGGG 
                 1425 
                 TCACTTTC 
               
               
                   
               
               
                 SEQ ID 
                 GCCAGTCAGAGTATTAGCAGCAACTTA 
                 SEQ ID 1361 
                 GGTGCATCCAGCAGGGCC 
                 SEQ ID 
                 CAGTATGGTAGCTCACTCC 
               
               
                 1287 
                 GCCTGG 
                   
                 ACTGGC 
                 1426 
                 TCTTC 
               
               
                   
               
               
                 SEQ ID 
                 TCTAGTCATAGCCTCACAACTACTGAT 
                 SEQ ID 1362 
                 GGTGCATCCACCAGGGCC 
                 SEQ ID 
                 CAGAGTAGTAGTTTACCTC 
               
               
                 1288 
                 GGACGTACTTACGTGGCTTGG 
                   
                 ACTGGT 
                 1427 
                 ACACTTTC 
               
               
                   
               
               
                 SEQ ID 
                 TCTAGTCAGAGCCTCCTGGGTGGTGAT 
                 SEQ ID 1363 
                 GAGGTTTCTAACCGGGAC 
                 SEQ ID 
                 CAGTATGGTAACTCACCTC 
               
               
                 1289 
                 GGAAAGACCTATTTGTATTGG 
                   
                 TCTGGT 
                 1428 
                 CGGGAGCCACCTTC 
               
               
                   
               
               
                 SEQ ID 
                 GCGAGTCAGGGCATTGCCAATTATTTA 
                 SEQ ID 1364 
                 GGCGCATCCAACAGGGC 
                 SEQ ID 
                 CAGTATCAAAGTTACTGG 
               
               
                 1290 
                 GCCTGG 
                   
                 CACAGGC 
                 1429 
                 ACGTTC 
               
               
                   
               
               
                 SEQ ID 
                 GCCAGTCAGAGTATTACTACCTGGTTG 
                 SEQ ID 1365 
                 GATGCGTCCAGCAGGGCC 
                 SEQ ID 
                 CACTATGGCAGCTCTCGC 
               
               
                 1291 
                 GCCTGG 
                   
                 GAAGGC 
                 1430 
                 ACCTTC 
               
               
                   
               
               
                 SEQ ID 
                 GCCAGTCAGAGTATTAGTAGCTGGTTG 
                 SEQ ID 1366 
                 CGTGCATCCAGCAGGGCC 
                 SEQ ID 
                 CAGTTTAATACCTACCCCA 
               
               
                 1292 
                 GCCTGG 
                   
                 ACTGGC 
                 1431 
                 ACACTTTT 
               
               
                   
               
               
                 SEQ ID 
                 GCCAGTCAGAGTGTTAATAGCGGCTAC 
                 SEQ ID 1367 
                 TCTACATCGACTTTACAA 
                 SEQ ID 
                 CAGTATGGTAGCTCACCT 
               
               
                 1293 
                 TTAGCCTGG 
                   
                 AGTGGA 
                 1432 
                 GCGCTCACTTTC 
               
               
                   
               
               
                 SEQ ID 
                 GCCAGTCACAGTGTTGGCGCCAACTAC 
                 SEQ ID 1368 
                 TGGGCATCTACCCGGGAC 
                 SEQ ID 
                 CAGTATGGTAGTCCACCTC 
               
               
                 1294 
                 ATAGCCTGG 
                   
                 TCCGGG 
                 1433 
                 CGACCACCTTC 
               
               
                   
               
               
                 SEQ ID 
                 TCTAGTCAGAGCCTCCTGCATAGTAAT 
                 SEQ ID 1369 
                 GATGCATCCAACAGGGCC 
                 SEQ ID 
                 CAGTATGGTAGCTCACCTC 
               
               
                 1295 
                 GGATACAACTATTTGGATTGG 
                   
                 ACTGGC 
                 1434 
                 GGGTCACTTTC 
               
               
                   
               
               
                 SEQ ID 
                 GCCAGTCAGAGTGTTAGCAGCAACTTA 
                 SEQ ID 1370 
                 CGTGCATCCACCAGGGCC 
                 SEQ ID 
                 CAGCGTGCCGAGTGGCCT 
               
               
                 1296 
                 GCCTGG 
                   
                 GCTGGT 
                 1435 
                 CTCACCTTC 
               
               
                   
               
               
                 SEQ ID 
                 GCCAGTCAGAGTGTAATAAGCAGGTAC 
                 SEQ ID 1371 
                 GATGCATCCAATTTGGAA 
                 SEQ ID 
                 CAGTATGGTAGCTCACGT 
               
               
                 1297 
                 TTAGCCTGG 
                   
                 ACAGGG 
                 1436 
                 CGGACGTTC 
               
               
                   
               
               
                 SEQ ID 
                 TCTAGTCAAAGCCTCGTACACAGTAAT 
                 SEQ ID 1372 
                 TTGGGTTCTAATCGGGCC 
                 SEQ ID 
                 CAGTATGGTAGCTCAGGG 
               
               
                 1298 
                 GGACACACCTACTTGAGTTGG 
                   
                 CCCGGG 
                 1437 
                 TACACTTTT 
               
               
                   
               
               
                 SEQ ID 
                 GCCAGTCAGAGTGTTAGCAGCAGCTAC 
                   
                   
                 SEQ ID 
                 CAGTATGGTAACTCACAG 
               
               
                 1299 
                 TTAGCCTGG 
                   
                   
                 1438 
                 ACCTTC 
               
               
                   
               
               
                 SEQ ID 
                 GCCAGTCAGAGTTTAAGTACCAACTTA 
                   
                   
                 SEQ ID 
                 CAATTTTATGGTATTCCCC 
               
               
                 1300 
                 GCCTGG 
                   
                   
                 1439 
                 ACTTC 
               
               
                   
               
               
                 SEQ ID 
                 GCCAGTCAGAGTATTAGCGGCAGTTAC 
                   
                   
                 SEQ ID 
                 AAGTATAACAGTCCCCCT 
               
               
                 1301 
                 TTAGCCTGG 
                   
                   
                 1440 
                 CGGACGTTC 
               
               
                   
               
               
                 SEQ ID 
                 GCCAGTCAGAGTCTTACCAGCAGCTAC 
                   
                   
                 SEQ ID 
                 CAAGGTCTACAAACTCCA 
               
               
                 1302 
                 TTAGCCTGG 
                   
                   
                 1441 
                 TTCACTTTC 
               
               
                   
               
               
                 SEQ ID 
                 TCCAGCCAGGCCCTGCGAAATGTTGTC 
                   
                   
                 SEQ ID 
                 CAGCGTAGCAACTGGCCT 
               
               
                 1303 
                 GGCCTTGGCGATGATTTAGCCTGG 
                   
                   
                 1442 
                 TTCTTC 
               
               
                   
               
               
                 SEQ ID 
                 TCCAACCGGAGTGTTTTATACAGCCCC 
                   
                   
                 SEQ ID 
                 CAGTATGGTATCTCACCTC 
               
               
                 1304 
                 AACAATCAGAACTACTTAGGTTGG 
                   
                   
                 1443 
                 TCGCGTTC 
               
               
                   
               
               
                 SEQ ID 
                 GCCAGTCAGAGTGTTAGCAGCTACTTA 
                   
                   
                 SEQ ID 
                 CAGAGTATCAGTTTACCG 
               
               
                 1305 
                 GCCTGG 
                   
                   
                 1444 
                 CTCACTTTC 
               
               
                   
               
               
                 SEQ ID 
                 GCCAGTCAGAGTGTTGGCAGCGACTTA 
                   
                   
                 SEQ ID 
                 CAATTTTATAGTCCTCCTC 
               
               
                 1306 
                 GCCTGG 
                   
                   
                 1445 
                 GGACGTTC 
               
               
                   
               
               
                 SEQ ID 
                 GCCAGTCAGAGTATTAGTAGCTGCTTG 
                   
                   
                 SEQ ID 
                 CAGTATAATAACTGGCCT 
               
               
                 1307 
                 GCCTGG 
                   
                   
                 1446 
                 AGAACGTTC 
               
               
                   
               
               
                   
                   
                   
                   
                 SEQ ID 
                 CAAGGAACACATGGGCCT 
               
               
                   
                   
                   
                   
                 1447 
                 CACACGTTC 
               
               
                   
               
               
                   
                   
                   
                   
                 SEQ ID 
                 CAATCTACACAATTTCCGT 
               
               
                   
                   
                   
                   
                 1448 
                 GGACGTTC 
               
               
                   
               
               
                   
                   
                   
                   
                 SEQ ID 
                 AAGTATAACAGTGTCCCT 
               
               
                   
                   
                   
                   
                 1449 
                 CTCACTTTC 
               
               
                   
               
               
                   
                   
                   
                   
                 SEQ ID 
                 CATTATAATGGTGCTTCTC 
               
               
                   
                   
                   
                   
                 1450 
                 GTATGTTC 
               
               
                   
               
               
                   
                   
                   
                   
                 SEQ ID 
                 CAGTATAATAGTTATTGG 
               
               
                   
                   
                   
                   
                 1451 
                 ACGTTC 
               
               
                   
               
               
                   
                   
                   
                   
                 SEQ ID 
                 CAAGCTCTACACACTCCGT 
               
               
                   
                   
                   
                   
                 1452 
                 GGACGTTC 
               
               
                   
               
               
                   
                   
                   
                   
                 SEQ ID 
                 CAGTATAATAGTTATTCAA 
               
               
                   
                   
                   
                   
                 1453 
                 GGACGTTC 
               
               
                   
               
               
                   
                   
                   
                   
                 SEQ ID 
                 CAGTATGGTAGCTCACTC 
               
               
                   
                   
                   
                   
                 1454 
                 AGGTACACTTTT 
               
               
                   
               
               
                   
                   
                   
                   
                 SEQ ID 
                 CAGTATAATAACTGGCCT 
               
               
                   
                   
                   
                   
                 1455 
                 CGGTTC 
               
               
                   
               
               
                   
                   
                   
                   
                 SEQ ID 
                 GAGTATGGTAACTCAGCT 
               
               
                   
                   
                   
                   
                 1456 
                 ATGTACAATTTT 
               
               
                   
               
               
                   
                   
                   
                   
                 SEQ ID 
                 CAGTATAATAACTGGCCT 
               
               
                   
                   
                   
                   
                 1457 
                 CTCACTTTC 
               
               
                   
               
               
                   
                   
                   
                   
                 SEQ ID 
                 CAGTATGCTGCCGCACCG 
               
               
                   
                   
                   
                   
                 1458 
                 ATTACCTTC 
               
               
                   
               
               
                   
                   
                   
                   
                 SEQ ID 
                 CAAACTTTACACACTGTCA 
               
               
                   
                   
                   
                   
                 1459 
                 CTTTC 
               
               
                   
               
               
                   
                   
                   
                   
                 SEQ ID 
                 CAGTATGGTAGCTCACCC 
               
               
                   
                   
                   
                   
                 1460 
                 CGGATCACCTTC 
               
               
                   
               
               
                   
                   
                   
                   
                 SEQ ID 
                 CAGTATAATAACTGGCCC 
               
               
                   
                   
                   
                   
                 1461 
                 CGGACGTTC 
               
               
                   
               
               
                   
                   
                   
                   
                 SEQ ID 
                 CAGTATAATAACTGGCCT 
               
               
                   
                   
                   
                   
                 1462 
                 CCTATGTACACTTTT 
               
               
                   
               
               
                   
                   
                   
                   
                 SEQ ID 
                 CAGTATGGTAGCTCACCTC 
               
               
                   
                   
                   
                   
                 1463 
                 CGTACACTTTT 
               
               
                   
               
               
                   
                   
                   
                   
                 SEQ ID 
                 CAAACTCTTCAAACTCCGC 
               
               
                   
                   
                   
                   
                 1464 
                 TCACTTTC 
               
               
                   
               
               
                   
                   
                   
                   
                 SEQ ID 
                 CAAGGAACACACTGGCCC 
               
               
                   
                   
                   
                   
                 1465 
                 CCCCTCACTGTC 
               
               
                   
               
               
                   
                   
                   
                   
                 SEQ ID 
                 CAGTATGGAAGCTCACCG 
               
               
                   
                   
                   
                   
                 1466 
                 GGAACGTTC 
               
               
                   
               
               
                   
                   
                   
                   
                 SEQ ID 
                 CAGTATCATAACTGGCCTC 
               
               
                   
                   
                   
                   
                 1467 
                 CGTACACTTTT 
               
               
                   
               
               
                   
                   
                   
                   
                 SEQ ID 
                 CAATATTATAGTAGTACTC 
               
               
                   
                   
                   
                   
                 1468 
                 CGTACACTTTT 
               
               
                   
               
               
                   
                   
                   
                   
                 SEQ ID 
                 CAGTATGGTAGCTCACCA 
               
               
                   
                   
                   
                   
                 1469 
                 ATATTCACTTTC 
               
               
                   
               
               
                   
                   
                   
                   
                 SEQ ID 
                 CAGTATGGTAGTTCACCTA 
               
               
                   
                   
                   
                   
                 1470 
                 ACACCTTC 
               
               
                   
               
               
                   
                   
                   
                   
                 SEQ ID 
                 CAGCACCATGATTTCCCTT 
               
               
                   
                   
                   
                   
                 1471 
                 TCACTTTC 
               
               
                   
               
               
                   
                   
                   
                   
                 SEQ ID 
                 CAGCGTTACAACTGGCCT 
               
               
                   
                   
                   
                   
                 1472 
                 ATCACCTTC 
               
               
                   
               
               
                   
                   
                   
                   
                 SEQ ID 
                 CAATATGCAAGTACTCCA 
               
               
                   
                   
                   
                   
                 1473 
                 TACACTTTT 
               
               
                   
               
               
                   
                   
                   
                   
                 SEQ ID 
                 CAGCGTAGCAACTGGCCT 
               
               
                   
                   
                   
                   
                 1474 
                 CGGACGTTC 
               
               
                   
               
               
                   
                   
                   
                   
                 SEQ ID 
                 CAGTATGGTAGATCACCG 
               
               
                   
                   
                   
                   
                 1475 
                 TACACTTCT 
               
               
                   
               
               
                   
                   
                   
                   
                 SEQ ID 
                 CAGTTTGATAATGTCCCAG 
               
               
                   
                   
                   
                   
                 1476 
                 TCACTTTC 
               
               
                   
               
               
                   
                   
                   
                   
                 SEQ ID 
                 CAGCTTAATAGTTACCCTC 
               
               
                   
                   
                   
                   
                 1477 
                 AGACGTTC 
               
               
                   
               
               
                   
                   
                   
                   
                 SEQ ID 
                 CAAGCTCTACAAACTCCG 
               
               
                   
                   
                   
                   
                 1478 
                 TACACTTTT 
               
               
                   
               
               
                   
                   
                   
                   
                 SEQ ID 
                 CAGTATAATAACTGGCCT 
               
               
                   
                   
                   
                   
                 1479 
                 CCGATCACCTTC 
               
               
                   
               
               
                   
                   
                   
                   
                 SEQ ID 
                 CAAGCTCTACAAACTCGG 
               
               
                   
                   
                   
                   
                 1480 
                 ACATTC 
               
               
                   
               
            
           
         
       
     
     In some embodiments, a nucleotide sequence encoding an antibody, antibody fragment, VH domain, VL domain or CDR of the disclosure is a wild type sequence. In some embodiments, the nucleotide sequence is codon optimized for expression in mammalian cells. In some embodiments, the nucleotide sequence is codon optimized for expression in human cells. 
     In some embodiments, the invention relates to an antibody that is capable of binding to CLEC2D and that blocks the interaction between CLEC2D and CD161 ( FIG. 1 ). In some embodiments, the anti-CLEC2D antibody as disclosed herein, is a monoclonal antibody. In some embodiments, the anti-CLEC2D antibody as disclosed herein, is a polyclonal antibody. 
     In some embodiments, the invention relates to an antibody that is capable of binding to CLEC2D and that blocks the interaction between CLEC2D and CD161, which is capable of removing CLEC2D-expressing cells by means of antibody-dependent cell-mediated cytotoxicity (ADCC) and/or by complement-dependent cytotoxicity (CDC). In some embodiments, the invention relates to an antibody that is capable of binding to CLEC2D and that blocks the interaction between CLEC2D and CD161, that is capable of stimulating the cytokine production and the cytotoxicity mediated by NK cells. 
     In some embodiments, the anti-CLEC2D antibody as disclosed herein, is a humanized antibody. In some embodiments, the anti-CLEC2D antibody as disclosed herein, is of human IgG1, IgG1 N296A, IgG2, IgG3 or IgG4 isotype. In some embodiments, the anti-CLEC2D antibody is a mouse IgG1, IgG2a, IgG2b or IgG3 isotype. 
     In some embodiments, an anti-CLEC2D antibody as disclosed herein, comprises a variable heavy chain (VH) comprising an amino acid sequence having at least 50% identity, at least 55% identity, at least 60% identity, at least 65% identity, at least 70% identity, at least 75% identity, at least 80% identity, at least 85% identity, at least 90% identity, at least 91% identity, at least 92% identity, at least 93% identity, at least 94% identity, at least 95% identity, at least 96% identity, at least 97% identity, at least 98% identity, at least 99% identity, at least 99.5% identity, at least 99.8% identity, at least 99.9% identity or 100% identity to an amino acid sequence selected from the group consisting of SEQ ID NOs: 1-108. 
     In some embodiments, an anti-CLEC2D antibody as disclosed herein, comprises a variable light chain (VL) comprising an amino acid sequence having at least 50% identity, at least 55% identity, at least 60% identity, at least 65% identity, at least 70% identity, at least 75% identity, at least 80% identity, at least 85% identity, at least 90% identity, at least 91% identity, at least 92% identity, at least 93% identity, at least 94% identity, at least 95% identity, at least 96% identity, at least 97% identity, at least 98% identity, at least 99% identity, at least 99.5% identity, at least 99.8% identity, at least 99.9% identity or 100% identity to an amino acid sequence selected from the group consisting of SEQ ID NOs. 217-324. 
     In some embodiments, an anti-CLEC2D antibody as disclosed herein, comprises a variable heavy chain (VH) comprising an amino acid sequence having at least 50% identity, at least 55% identity, at least 60% identity, at least 65% identity, at least 70% identity, at least 75% identity, at least 80% identity, at least 85% identity, at least 90% identity, at least 91% identity, at least 92% identity, at least 93% identity, at least 94% identity, at least 95% identity, at least 96% identity, at least 97% identity, at least 98% identity, at least 99% identity, at least 99.5% identity, at least 99.8% identity, at least 99.9% identity or 100% identity to an amino acid sequence selected from the group consisting of SEQ ID NOs: 1-108; and a variable light chain (VL) comprising an amino acid sequence having at least 50% identity, at least 55% identity, at least 60% identity, at least 65% identity, at least 70% identity, at least 75% identity, at least 80% identity, at least 85% identity, at least 90% identity, at least 91% identity, at least 92% identity, at least 93% identity, at least 94% identity, at least 95% identity, at least 96% identity, at least 97% identity, at least 98% identity, at least 99% identity, at least 99.5% identity, at least 99.8% identity, at least 99.9% identity or 100% identity to an amino acid sequence selected from the group consisting of SEQ ID NOs: 217-324. 
     In some embodiments, an anti-CLEC2D antibody as disclosed herein, comprises a variable heavy chain (VH) comprising an amino acid sequence encoded by a nucleic acid selected from the group consisting of SEQ ID NOs: 109-216. 
     In some embodiments, an anti-CLEC2D antibody as disclosed herein, comprises a variable light chain (VL) comprising an amino acid sequence encoded by a nucleic acid selected from the group consisting of SEQ ID NOs: 325-432. 
     In some embodiments, an anti-CLEC2D antibody as disclosed herein, comprises a variable heavy chain (VH) comprising an amino acid sequence encoded by a nucleic acid selected from the group consisting of SEQ ID NOs: 109-216; and a variable light chain (VL) comprising an amino acid sequence encoded by a nucleic acid selected from the group consisting of SEQ ID NOs: 325-432. 
     In some embodiments, an anti-CLEC2D antibody as disclosed herein, comprises a variable heavy chain (VH) comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 1-108. 
     In some embodiments, an anti-CLEC2D antibody as disclosed herein, comprises a variable light chain (VL) comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 217-324. 
     In some embodiments, an anti-CLEC2D antibody as disclosed herein, comprises a variable heavy chain (VH) comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 1-108, and a variable light chain (VL) comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 217-324. 
     In some embodiments, an anti-CLEC2D antibody as disclosed herein, comprises a VH comprising an amino acid sequence according to SEQ ID NO 44 and a VL comprising an amino acid sequence according to SEQ ID NO: 260. 
     In some embodiments, an anti-CLEC2D antibody as disclosed herein, comprises a VH comprising an amino acid sequence according to SEQ ID NO:45, and a VL comprising an amino acid sequence according to SEQ ID NO:261. 
     In some embodiments, an anti-CLEC2D antibody as disclosed herein, comprises a VH comprising an amino acid sequence according to SEQ ID NO:42, and a VL comprising an amino acid sequence according to SEQ ID NO: 258. 
     In some embodiments, an anti-CLEC2D antibody as disclosed herein, comprises a VH comprising an amino acid sequence according to SEQ ID NO:1, and a VL comprising an amino acid sequence according to SEQ ID NO: 217. 
     In some embodiments, an anti-CLEC2D antibody as disclosed herein, comprises a VH comprising an amino acid sequence according to SEQ ID NO:73, and a VL comprising an amino acid sequence according to SEQ ID NO:289. 
     In some embodiments, an anti-CLEC2D antibody as disclosed herein, comprises a VH comprising an amino acid sequence according to SEQ ID NO:21, and a VL comprising an amino acid sequence according to SEQ ID NO:237. 
     In some embodiments, an anti-CLEC2D antibody as disclosed herein, comprises a VH comprising an amino acid sequence according to SEQ ID NO:35, and a VL comprising an amino acid sequence according to SEQ ID NO:251. 
     In some embodiments, an anti-CLEC2D antibody as disclosed herein, comprises a VH comprising an amino acid sequence according to SEQ ID NO:58, and a VL comprising an amino acid sequence according to SEQ ID NO: 274. 
     In some embodiments, an anti-CLEC2D antibody as disclosed herein, comprises a VH comprising an amino acid sequence according to SEQ ID NO:7, and a VL comprising an amino acid sequence according to SEQ ID NO:223. 
     In some embodiments, an anti-CLEC2D antibody as disclosed herein, comprises a Variable heavy chain (VH) complementarity determining region 1 (CDR1) comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 433-485. 
     In some embodiments, an anti-CLEC2D antibody as disclosed herein, comprises a Variable heavy chain (VH) complementarity determining region 2 (CDR2) comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 486-546. 
     In some embodiments, an anti-CLEC2D antibody as disclosed herein, comprises a Variable heavy chain (VH) complementarity determining region 3 (CDR3) comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 547-653. 
     In some embodiments, an anti-CLEC2D antibody as disclosed herein, comprises a variable light chain (VL) complementarity determining region 1 (CDR1) comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 654-726. 
     In some embodiments, an anti-CLEC2D antibody as disclosed herein, comprises a variable light chain (VL) complementarity determining region 2 (CDR2) comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 727-783. 
     In some embodiments, an anti-CLEC2D antibody as disclosed herein, comprises a variable light chain (VL) complementarity determining region 3 (CDR3) comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 784-885. 
     In some embodiments, an anti-CLEC2D antibody as disclosed herein, comprises a Variable heavy chain (VH) complementarity determining region 1 (CDR1) comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 433-485, a VH complementarity determining region 2 (CDR2) comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 486-546, and a VH complementarity determining region 3 (CDR3) comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 547-653. 
     In some embodiments, an anti-CLEC2D antibody as disclosed herein, comprises a Variable Light chain (VL) complementarity determining region 1 (CDR1) comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 654-726, a VL complementarity determining region 2 (CDR2) comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 727-783, and a VL complementarity determining region 3 (CDR3) comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 784-885. 
     In some embodiments, an anti-CLEC2D antibody as disclosed herein, comprises a variable heavy chain (VH) complementarity determining region 1 (CDR1) comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 433-485, a VH complementarity determining region 2 (CDR2) comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 486-546, and a VH complementarity determining region 3 (CDR3) comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 547-653; and a variable light chain (VL) complementarity determining region 1 (CDR1) comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 654-726, a VL complementarity determining region 2 (CDR2) comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 727-783, and a VL complementarity determining region 3 (CDR3) comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 784-885. 
     In some embodiments, an anti-CLEC2D antibody as disclosed herein, comprises a VH CDR1 comprising an amino acid sequence according to the SEQ ID NO: 439, a VH CDR2 comprising an amino acid according to the SEQ ID NO:492, and a VH CDR3 comprising an amino acid sequence according to the SEQ ID NOs: 589; and a VL CDR1 comprising an amino acid sequence according to SEQ ID NO: 687, a VL CDR2 comprising an amino acid sequence according to SEQ ID NOs: 729, and a VL CDR3 comprising an amino acid sequence according to SEQ ID NOs: 827. 
     In some embodiments, an anti-CLEC2D antibody as disclosed herein, comprises a VH CDR1 comprising an amino acid sequence according to the SEQ ID NO: 439, a VH CDR2 comprising an amino acid according to the SEQ ID NO: 492, and a VH CDR3 comprising an amino acid sequence according to the SEQ ID NOs: 590; and a VL CDR1 comprising an amino acid sequence according to SEQ ID 688, a VL CDR2 comprising an amino acid sequence according to SEQ ID 755, and a VL CDR3 comprising an amino acid sequence according to SEQ ID 828. 
     In some embodiments, an anti-CLEC2D antibody as disclosed herein, comprises a VH CDR1 comprising an amino acid sequence according to the SEQ ID 473, a VH CDR2 comprising an amino acid according to the SEQ ID 495, and a VH CDR3 comprising an amino acid sequence according to the SEQ ID 587; and a VL CDR1 comprising an amino acid sequence according to SEQ ID 655, a VL CDR2 comprising an amino acid sequence according to SEQ ID 732; and a VL CDR3 comprising an amino acid sequence according to SEQ ID 825. 
     In some embodiments, an anti-CLEC2D antibody as disclosed herein, comprises a VH CDR1 comprising an amino acid sequence according to the SEQ ID 433, a VH CDR2 comprising an amino acid according to the SEQ ID 486, and a VH CDR3 comprising an amino acid sequence according to the SEQ ID 547; and a VL CDR1 comprising an amino acid sequence according to SEQ ID 654, a VL CDR2 comprising an amino acid sequence according to SEQ ID 727, and a VL CDR3 comprising an amino acid sequence according to SEQ ID 784. 
     In some embodiments, an anti-CLEC2D antibody as disclosed herein, comprises a VH CDR1 comprising an amino acid sequence according to the SEQ ID 439, a VH CDR2 comprising an amino acid according to the SEQ ID 492, and a VH CDR3 comprising an amino acid sequence according to the SEQ ID 618; and a VL CDR1 comprising an amino acid sequence according to SEQ ID 678, a VL CDR2 comprising an amino acid sequence according to SEQ ID 730, and a VL CDR3 comprising an amino acid sequence according to SEQ ID 852. 
     In some embodiments, an anti-CLEC2D antibody as disclosed herein, comprises a VH CDR1 comprising an amino acid sequence according to the SEQ ID 446, a VH CDR2 comprising an amino acid according to the SEQ ID 501, and a VH CDR3 comprising an amino acid sequence according to the SEQ ID 567; and a VL CDR1 comprising an amino acid sequence according to SEQ ID 655, a VL CDR2 comprising an amino acid sequence according to SEQ ID 735, and a VL CDR3 comprising an amino acid sequence according to SEQ ID 804. 
     In some embodiments, an anti-CLEC2D antibody as disclosed herein, comprises a VH CDR1 comprising an amino acid sequence according to the SEQ ID 435, a VH CDR2 comprising an amino acid according to the SEQ ID 488, and a VH CDR3 comprising an amino acid sequence according to the SEQ ID 581; and a VL CDR1 comprising an amino acid sequence according to SEQ ID 680, a VL CDR2 comprising an amino acid sequence according to SEQ ID 782, and a VL CDR3 comprising an amino acid sequence according to SEQ ID 818. 
     In some embodiments, an anti-CLEC2D antibody as disclosed herein, comprises a VH CDR1 comprising an amino acid sequence according to the SEQ ID 466, a VH CDR2 comprising an amino acid according to SEQ ID 521, and a VH CDR3 comprising an amino acid sequence according to the SEQ ID 603; and a VL CDR1 comprising an amino acid sequence according to the SEQ ID 662, a VL CDR2 comprising an amino acid sequence according to the SEQ ID 732, and a VL CDR3 comprising an amino acid sequence according to the SEQ ID 814. 
     In some embodiments, an anti-CLEC2D antibody as disclosed herein, comprises a VH CDR1 comprising an amino acid sequence according to the SEQ ID 439, a VH CDR2 comprising an amino acid according to the SEQ ID 492, and a VH CDR3 comprising an amino acid sequence according to the SEQ ID 553; and a VL CDR1 comprising an amino acid sequence according to the SEQ ID 660, a VL CDR2 comprising an amino acid sequence according to the SEQ ID 733, and a VL CDR3 comprising an amino acid sequence according to the SEQ ID 790. 
     The disclosure provides an antibody library comprising at least about 108 unique monoclonal antibody clones, wherein at least about 80% of the antibody clones detectably and specifically bind a CLEC2D antigen. Various anti-CLEC2D antibodies with specific combinations of heavy chain, light chain, heavy chain CDRs 1-3 (i.e., CDRH1, CDRH2, and CDRH3) and Light clain CDRs 1-3 (i.e., CDRL1, CDRL2, and CDRL3), are described in Table 9A. 
     
       
         
           
               
               
               
               
               
               
               
               
               
               
               
             
               
                 TABLE 9A 
               
               
                   
               
               
                 Anti-  
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 CLEC2D 
                 SEQ ID 
                   
                 SEQ ID 
                   
                   
                   
                   
                   
                   
                   
               
               
                 antibody 
                 code 
                 SEQ ID  
                 LC AA 
                 SEQ ID  
                 SEQ ID 
                 SEQ ID  
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID  
               
               
                 No. 
                 HC AA 
                 HC DNA 
                 SEQ ID 
                 LC DNA 
                 CDRH1 
                 CDRH2 
                 CDRH3 
                 CDRL1 
                 CDRL2 
                 CDRL3 
               
               
                   
               
             
            
               
                 A1 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
               
               
                   
                 44 
                 152 
                 260 
                 368 
                 439 
                 492 
                 589 
                 687 
                 729 
                 827 
               
               
                 B1 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
               
               
                   
                 45 
                 153 
                 261 
                 369 
                 439 
                 492 
                 590 
                 688 
                 755 
                 828 
               
               
                 C1 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
               
               
                   
                 75 
                 183 
                 291 
                 399 
                 453 
                 507 
                 620 
                 700 
                 760 
                 854 
               
               
                 D1 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
               
               
                   
                 77 
                 185 
                 293 
                 401 
                 439 
                 492 
                 622 
                 706 
                 769 
                 856 
               
               
                 E1 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
               
               
                   
                 42 
                 150 
                 258 
                 366 
                 473 
                 495 
                 587 
                 655 
                 732 
                 825 
               
               
                 F1 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
               
               
                   
                 56 
                 164 
                 272 
                 380 
                 433 
                 486 
                 601 
                 662 
                 754 
                 838 
               
               
                 G1 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
               
               
                   
                 64 
                 172 
                 280 
                 388 
                 469 
                 525 
                 609 
                 655 
                 735 
                 844 
               
               
                 H1 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
               
               
                   
                 50 
                 158 
                 266 
                 374 
                 456 
                 512 
                 595 
                 692 
                 759 
                 833 
               
               
                 I1 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
               
               
                   
                 43 
                 151 
                 259 
                 367 
                 473 
                 49S 
                 588 
                 686 
                 754 
                 826 
               
               
                 J1 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
               
               
                   
                 80 
                 188 
                 296 
                 404 
                 437 
                 506 
                 625 
                 708 
                 771 
                 859 
               
               
                 K1 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
               
               
                   
                 33 
                 141 
                 249 
                 357 
                 454 
                 510 
                 579 
                 655 
                 735 
                 816 
               
               
                 L1 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
               
               
                   
                 23 
                 131 
                 239 
                 347 
                 439 
                 492 
                 569 
                 670 
                 744 
                 806 
               
               
                 M1 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
               
               
                   
                 24 
                 132 
                 240 
                 348 
                 448 
                 504 
                 570 
                 656 
                 729 
                 807 
               
               
                 N1 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
               
               
                   
                 59 
                 167 
                 275 
                 383 
                 461 
                 516 
                 604 
                 696 
                 742 
                 840 
               
               
                 O1 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
               
               
                   
                 74 
                 182 
                 290 
                 398 
                 474 
                 530 
                 619 
                 705 
                 743 
                 853 
               
               
                 P1 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
               
               
                   
                 1 
                 109 
                 217 
                 325 
                 433 
                 486 
                 547 
                 654 
                 727 
                 784 
               
               
                 Q1 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
               
               
                   
                 25 
                 133 
                 241 
                 349 
                 449 
                 505 
                 571 
                 671 
                 745 
                 808 
               
               
                 R1 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
               
               
                   
                 61 
                 169 
                 277 
                 385 
                 437 
                 529 
                 606 
                 698 
                 764 
                 842 
               
               
                 S1 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
               
               
                   
                 60 
                 168 
                 276 
                 384 
                 467 
                 522 
                 605 
                 697 
                 763 
                 841 
               
               
                 T1 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
               
               
                   
                 28 
                 136 
                 244 
                 352 
                 451 
                 507 
                 574 
                 674 
                 747 
                 811 
               
               
                 U1 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
               
               
                   
                 73 
                 181 
                 289 
                 397 
                 439 
                 492 
                 618 
                 678 
                 730 
                 852 
               
               
                 V1 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
               
               
                   
                 4 
                 112 
                 220 
                 328 
                 436 
                 489 
                 550 
                 657 
                 730 
                 787 
               
               
                 W1 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
               
               
                   
                 6 
                 114 
                 222 
                 330 
                 438 
                 491 
                 552 
                 659 
                 732 
                 789 
               
               
                 X1 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
               
               
                   
                 46 
                 154 
                 262 
                 370 
                 461 
                 516 
                 591 
                 689 
                 756 
                 829 
               
               
                 Y1 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
               
               
                   
                 21 
                 129 
                 237 
                 345 
                 446 
                 501 
                 567 
                 655 
                 735 
                 804 
               
               
                 Z1 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
               
               
                   
                 63 
                 171 
                 279 
                 387 
                 468 
                 524 
                 608 
                 655 
                 735 
                 843 
               
               
                 A2 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
               
               
                   
                 57 
                 165 
                 273 
                 381 
                 461 
                 516 
                 602 
                 695 
                 762 
                 839 
               
               
                 B2 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
               
               
                   
                 47 
                 155 
                 263 
                 371 
                 462 
                 517 
                 592 
                 656 
                 729 
                 830 
               
               
                 C2 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
               
               
                   
                 83 
                 191 
                 299 
                 407 
                 433 
                 486 
                 628 
                 656 
                 729 
                 862 
               
               
                 D2 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
               
               
                   
                 29 
                 137 
                 245 
                 353 
                 434 
                 508 
                 575 
                 675 
                 748 
                 812 
               
               
                 E2 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
               
               
                   
                 35 
                 143 
                 251 
                 359 
                 435 
                 488 
                 581 
                 680 
                 782 
                 818 
               
               
                 F2 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
               
               
                   
                 81 
                 189 
                 297 
                 405 
                 475 
                 532 
                 626 
                 655 
                 729 
                 860 
               
               
                 G2 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
               
               
                   
                 76 
                 184 
                 292 
                 400 
                 453 
                 531 
                 621 
                 662 
                 732 
                 855 
               
               
                 H2 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
               
               
                   
                 36 
                 144 
                 252 
                 360 
                 456 
                 512 
                 582 
                 681 
                 751 
                 819 
               
               
                 I2 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
               
               
                   
                 58 
                 166 
                 274 
                 382 
                 466 
                 521 
                 603 
                 662 
                 732 
                 814 
               
               
                 J2 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
               
               
                   
                 52 
                 160 
                 268 
                 376 
                 450 
                 506 
                 597 
                 667 
                 734 
                 835 
               
               
                 K2 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
               
               
                   
                 71 
                 179 
                 287 
                 395 
                 437 
                 529 
                 616 
                 703 
                 767 
                 850 
               
               
                 L2 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
               
               
                   
                 7 
                 115 
                 223 
                 331 
                 439 
                 492 
                 553 
                 660 
                 733 
                 790 
               
               
                 M2 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
               
               
                   
                 72 
                 180 
                 288 
                 396 
                 473 
                 495 
                 617 
                 704 
                 768 
                 851 
               
               
                 N2 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
               
               
                   
                 62 
                 170 
                 278 
                 386 
                 450 
                 523 
                 607 
                 662 
                 732 
                 834 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 9B 
               
             
            
               
                   
               
               
                 Germline information of selected anti-CLEC2D  
               
               
                 antibodies from Table 9A 
               
            
           
           
               
               
               
            
               
                 Anti-CLEC2D  
                 Variable  
                 Variable  
               
               
                 antibody  
                 Heavy chain 
                 Light chain 
               
               
                 No* (Selected  
                 Framework— 
                 Framework— 
               
               
                 Antibodies 
                 Germline  
                 Germline  
               
               
                 from Table 9A) 
                 Family Information 
                 Family Information 
               
               
                   
               
               
                 A1 
                 IGHV4; IGHD3; IGHJ2 
                 IGKV3; IGKJ4 
               
               
                 B1 
                 IGHV4; IGHD3; IGHJ5 
                 IGKV1; IGKJ1 
               
               
                 E1 
                 IGHV3; IGHD5; IGHJ4 
                 IGKV3; IGKJ5 
               
               
                 P1 
                 IGHV1; IGHD6; IGHJ4 
                 IGKV3; IGKJ5 
               
               
                 U1 
                 IGHV4; IGHD1; IGHJ4 
                 IGKV4; IGKJ4 
               
               
                 Y1 
                 IGHV5; IGHD5; IGHJ4 
                 IGKV3; IGKJ4 
               
               
                 E2 
                 IGHV1; IGHD5; IGHJ4 
                 IGKV1; IGKJ1 
               
               
                 I2 
                 IGHV6; IGHD1; IGHJ4 
                 IGKV3; IGKJ1 
               
               
                 L2 
                 IGHV4; IGHD3; IGHJ4 
                 IGKV1; IGKJ3 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 9C 
               
             
            
               
                   
               
               
                 Amino acid and DNA sequence information of anti-CLEC2D antibodies 
               
               
                 formatted as IgGl, IgG4, IgG N2A and IgG2. 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 Anti- 
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 CLEC2D 
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 No. * 
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 (Selected 
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 Antibodies 
                   
                   
                 IgG1 
                 IgG1 
                   
                 IgG4 
                   
                 IgG  
                   
                   
               
               
                 from Table 
                 IgG1 
                 IgG1 
                 HC 
                 LC 
                 IgG4 
                 HC 
                 IgG 
                 N2A 
                   
                 IgG2 
               
               
                 9A and 9B) 
                 HC 
                 LC 
                 DNA 
                 DNA 
                 HC 
                 DNA 
                 N2A 
                 DNA 
                 IgG2 
                 DNA 
               
               
                   
               
               
                 A1 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
               
               
                   
                 1524 
                 1632 
                 1740 
                 1848 
                 1956 
                 2064 
                 2172 
                 2280 
                 2388 
                 2496 
               
               
                 B1 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
               
               
                   
                 1525 
                 1633 
                 1741 
                 1849 
                 1957 
                 2065 
                 2173 
                 2281 
                 2389 
                 2497 
               
               
                 E1 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
               
               
                   
                 1522 
                 1630 
                 1738 
                 1846 
                 1954 
                 2062 
                 2170 
                 2278 
                 2386 
                 2494 
               
               
                 P1 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
               
               
                   
                 1481 
                 1589 
                 1697 
                 1805 
                 1913 
                 2021 
                 2129 
                 2237 
                 2345 
                 2453 
               
               
                 U1 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
               
               
                   
                 1553 
                 1661 
                 1769 
                 1877 
                 1985 
                 2093 
                 2201 
                 2309 
                 2417 
                 2525 
               
               
                 Y1 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
               
               
                   
                 1501 
                 1609 
                 1717 
                 1825 
                 1933 
                 2041 
                 2149 
                 2257 
                 2365 
                 2473 
               
               
                 E2 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
               
               
                   
                 1515 
                 1623 
                 1731 
                 1839 
                 1947 
                 2055 
                 2163 
                 2271 
                 2379 
                 2487 
               
               
                 I2 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
               
               
                   
                 1538 
                 1646 
                 1754 
                 1862 
                 1970 
                 2078 
                 2186 
                 2294 
                 2402 
                 2510 
               
               
                 L2 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
                 SEQ ID 
               
               
                   
                 1487 
                 1595 
                 1703 
                 1811 
                 1919 
                 2027 
                 2135 
                 2243 
                 2351 
                 2459 
               
               
                   
               
            
           
         
       
     
     In some embodiments, an anti-CLEC2D antibody, as disclosed herein, comprises a combination of heavy chain CDRs 1, 2 and 3, and light chain CDRs 1, 2 and 3, according to the amino acid sequence of the heavy chain CDRs 1, 2 and 3, and light chain CDRs 1, 2 and 3 of the anti-CLEC2D antibody No. A1, as disclosed in Table 9A. In some embodiments, an anti-CLEC2D antibody, as disclosed herein, comprises a combination of a heavy chain and a light chain, according to the amino acid sequence of the heavy chain and light chain of the anti-CLEC2D antibody No. A1, as disclosed in Table 9A. In some embodiments, the anti-CLEC2D antibody No. A1, as disclosed in Table 9B, comprises a variable heavy chain having a framework region sequence of the Germline gene families: IGHV4, IGHD3 and IGHJ2. In some embodiments, the anti-CLEC2D antibody No. A1, as disclosed in Table 9B, comprises a variable light chain having a framework region sequence of the Germline families: IGKV3 and IGKJ4. 
     In some embodiments, an anti-CLEC2D antibody, as disclosed herein, comprises a combination of heavy chain CDRs 1, 2 and 3, and light chain CDRs 1, 2 and 3, according to the amino acid sequence of the heavy chain CDRs 1, 2 and 3, and light chain CDRs 1, 2 and 3 of anti-CLEC2D antibody No. B1, as disclosed in Table 9A. In some embodiments, an anti-CLEC2D antibody, as disclosed herein, comprises a combination of a heavy chain and a light chain, according to the amino acid sequence of the heavy chain and light chain of anti-CLEC2D antibody No. B1, as disclosed in Table 9A. In some embodiments, the anti-CLEC2D antibody No. B1, as disclosed in Table 9B, comprises a variable heavy chain having a framework region sequence of the Germline gene families: IGHV4, IGHD3 and IGHJ5. In some embodiments, the anti-CLEC2D antibody No. B1, as disclosed in Table 9B, comprises a variable light chain having a framework region sequence of the Germline families: IGKV1 and IGKJ1. 
     In some embodiments, an anti-CLEC2D antibody, as disclosed herein, comprises a combination of heavy chain CDRs 1, 2 and 3, and light chain CDRs 1, 2 and 3, according to the amino acid sequence of the heavy chain CDRs 1, 2 and 3, and light chain CDRs 1, 2 and 3 of anti-CLEC2D antibody No. C1, as disclosed in Table 9A. In some embodiments, an anti-CLEC2D antibody, as disclosed herein, comprises a combination of a heavy chain and a light chain, according to the amino acid sequence of the heavy chain and light chain of anti-CLEC2D antibody No. C1, as disclosed in Table 9A. 
     In some embodiments, an anti-CLEC2D antibody, as disclosed herein, comprises a combination of heavy chain CDRs 1, 2 and 3, and light chain CDRs 1, 2 and 3, according to the amino acid sequence of the heavy chain CDRs 1, 2 and 3, and light chain CDRs 1, 2 and 3 of anti-CLEC2D antibody No. D1, as disclosed in Table 9A. In some embodiments, an anti-CLEC2D antibody, as disclosed herein, comprises a combination of a heavy chain and a light chain, according to the amino acid sequence of the heavy chain and light chain of anti-CLEC2D antibody No. D1, as disclosed in Table 9A. 
     In some embodiments, an anti-CLEC2D antibody, as disclosed herein, comprises a combination of heavy chain CDRs 1, 2 and 3, and light chain CDRs 1, 2 and 3, according to the amino acid sequence of the heavy chain CDRs 1, 2 and 3, and light chain CDRs 1, 2 and 3 of anti-CLEC2D antibody No. E1, as disclosed in Table 9A. In some embodiments, an anti-CLEC2D antibody, as disclosed herein, comprises a combination of a heavy chain and a light chain, according to the amino acid sequence of the heavy chain and light chain of anti-CLEC2D antibody No. E1, as disclosed in Table 9A. In some embodiments, the anti-CLEC2D antibody No. E1, as disclosed in Table 9B, comprises a variable heavy chain having a framework region sequence of the Germline gene families: IGHV3, IGHD5 and IGHJ4. In some embodiments, the anti-CLEC2D antibody No. E1, as disclosed in Table 9B, comprises a variable light chain having a framework region sequence of the Germline families: IGKV3 and IGKJ5. 
     In some embodiments, an anti-CLEC2D antibody, as disclosed herein, comprises a combination of heavy chain CDRs 1, 2 and 3, and light chain CDRs 1, 2 and 3, according to the amino acid sequence of the heavy chain CDRs 1, 2 and 3, and light chain CDRs 1, 2 and 3 of anti-CLEC2D antibody No. F1, as disclosed in Table 9A. In some embodiments, an anti-CLEC2D antibody, as disclosed herein, comprises a combination of a heavy chain and a light chain, according to the amino acid sequence of the heavy chain and light chain of anti-CLEC2D antibody No. F1, as disclosed in Table 9A. 
     In some embodiments, an anti-CLEC2D antibody, as disclosed herein, comprises a combination of heavy chain CDRs 1, 2 and 3, and light chain CDRs 1, 2 and 3, according to the amino acid sequence of the heavy chain CDRs 1, 2 and 3, and light chain CDRs 1, 2 and 3 of anti-CLEC2D antibody No. G1, as disclosed in Table 9A. In some embodiments, an anti-CLEC2D antibody, as disclosed herein, comprises a combination of a heavy chain and a light chain, according to the amino acid sequence of the heavy chain and light chain of anti-CLEC2D antibody No. G1, as disclosed in Table 9A. 
     In some embodiments, an anti-CLEC2D antibody, as disclosed herein, comprises a combination of heavy chain CDRs 1, 2 and 3, and light chain CDRs 1, 2 and 3, according to the amino acid sequence of the heavy chain CDRs 1, 2 and 3, and light chain CDRs 1, 2 and 3 of anti-CLEC2D antibody No. H1, as disclosed in Table 9A. In some embodiments, an anti-CLEC2D antibody, as disclosed herein, comprises a combination of a heavy chain and a light chain, according to the amino acid sequence of the heavy chain and light chain of anti-CLEC2D antibody No. H1, as disclosed in Table 9A. 
     In some embodiments, an anti-CLEC2D antibody, as disclosed herein, comprises a combination of heavy chain CDRs 1, 2 and 3, and light chain CDRs 1, 2 and 3, according to the amino acid sequence of the heavy chain CDRs 1, 2 and 3, and light chain CDRs 1, 2 and 3 of anti-CLEC2D antibody No. I1, as disclosed in Table 9A. In some embodiments, an anti-CLEC2D antibody, as disclosed herein, comprises a combination of a heavy chain and a light chain, according to the amino acid sequence of the heavy chain and light chain of anti-CLEC2D antibody No. I1, as disclosed in Table 9A. 
     In some embodiments, an anti-CLEC2D antibody, as disclosed herein, comprises a combination of heavy chain CDRs 1, 2 and 3, and light chain CDRs 1, 2 and 3, according to the amino acid sequence of the heavy chain CDRs 1, 2 and 3, and light chain CDRs 1, 2 and 3 of anti-CLEC2D antibody No. J1, as disclosed in Table 9A. In some embodiments, an anti-CLEC2D antibody, as disclosed herein, comprises a combination of a heavy chain and a light chain, according to the amino acid sequence of the heavy chain and light chain of anti-CLEC2D antibody No. J1, as disclosed in Table 9A. 
     In some embodiments, an anti-CLEC2D antibody, as disclosed herein, comprises a combination of heavy chain CDRs 1, 2 and 3, and light chain CDRs 1, 2 and 3, according to the amino acid sequence of the heavy chain CDRs 1, 2 and 3, and light chain CDRs 1, 2 and 3 of anti-CLEC2D antibody No. K1, as disclosed in Table 9A. In some embodiments, an anti-CLEC2D antibody, as disclosed herein, comprises a combination of a heavy chain and a light chain, according to the amino acid sequence of the heavy chain and light chain of anti-CLEC2D antibody No. K1, as disclosed in Table 9A. 
     In some embodiments, an anti-CLEC2D antibody, as disclosed herein, comprises a combination of heavy chain CDRs 1, 2 and 3, and light chain CDRs 1, 2 and 3, according to the amino acid sequence of the heavy chain CDRs 1, 2 and 3, and light chain CDRs 1, 2 and 3 of anti-CLEC2D antibody No. L1, as disclosed in Table 9A. In some embodiments, an anti-CLEC2D antibody, as disclosed herein, comprises a combination of a heavy chain and a light chain, according to the amino acid sequence of the heavy chain and light chain of anti-CLEC2D antibody No. L1, as disclosed in Table 9A. 
     In some embodiments, an anti-CLEC2D antibody, as disclosed herein, comprises a combination of heavy chain CDRs 1, 2 and 3, and light chain CDRs 1, 2 and 3, according to the amino acid sequence of the heavy chain CDRs 1, 2 and 3, and light chain CDRs 1, 2 and 3 of anti-CLEC2D antibody No. M1, as disclosed in Table 9A. In some embodiments, an anti-CLEC2D antibody, as disclosed herein, comprises a combination of a heavy chain and a light chain, according to the amino acid sequence of the heavy chain and light chain of anti-CLEC2D antibody No. M1, as disclosed in Table 9A. 
     In some embodiments, an anti-CLEC2D antibody, as disclosed herein, comprises a combination of heavy chain CDRs 1, 2 and 3, and light chain CDRs 1, 2 and 3, according to the amino acid sequence of the heavy chain CDRs 1, 2 and 3, and light chain CDRs 1, 2 and 3 of anti-CLEC2D antibody No. N1, as disclosed in Table 9A. In some embodiments, an anti-CLEC2D antibody, as disclosed herein, comprises a combination of a heavy chain and a light chain, according to the amino acid sequence of the heavy chain and light chain of anti-CLEC2D antibody No. N1, as disclosed in Table 9A. 
     In some embodiments, an anti-CLEC2D antibody, as disclosed herein, comprises a combination of heavy chain CDRs 1, 2 and 3, and light chain CDRs 1, 2 and 3, according to the amino acid sequence of the heavy chain CDRs 1, 2 and 3, and light chain CDRs 1, 2 and 3 of anti-CLEC2D antibody No. O1, as disclosed in Table 9A. In some embodiments, an anti-CLEC2D antibody, as disclosed herein, comprises a combination of a heavy chain and a light chain, according to the amino acid sequence of the heavy chain and light chain of anti-CLEC2D antibody No. O1, as disclosed in Table 9A. 
     In some embodiments, an anti-CLEC2D antibody, as disclosed herein, comprises a combination of heavy chain CDRs 1, 2 and 3, and light chain CDRs 1, 2 and 3, according to the amino acid sequence of the heavy chain CDRs 1, 2 and 3, and light chain CDRs 1, 2 and 3 of anti-CLEC2D antibody No. P1, as disclosed in Table 9A. In some embodiments, an anti-CLEC2D antibody, as disclosed herein, comprises a combination of a heavy chain and a light chain, according to the amino acid sequence of the heavy chain and light chain of anti-CLEC2D antibody No. P1, as disclosed in Table 9A. In some embodiments, the anti-CLEC2D antibody No. P1, as disclosed in Table 9B, comprises a variable heavy chain having a framework region sequence of the Germline gene families: IGHV1, IGHD6 and IGHJ4. In some embodiments, the anti-CLEC2D antibody No. P1, as disclosed in Table 9B, comprises a variable light chain having a framework region sequence of the Germline families: IGKV3 and IGKJ5. 
     In some embodiments, an anti-CLEC2D antibody, as disclosed herein, comprises a combination of heavy chain CDRs 1, 2 and 3, and light chain CDRs 1, 2 and 3, according to the amino acid sequence of the heavy chain CDRs 1, 2 and 3, and light chain CDRs 1, 2 and 3 of anti-CLEC2D antibody No. Q1, as disclosed in Table 9A. In some embodiments, an anti-CLEC2D antibody, as disclosed herein, comprises a combination of a heavy chain and a light chain, according to the amino acid sequence of the heavy chain and light chain of anti-CLEC2D antibody No. Q1, as disclosed in Table 9A. 
     In some embodiments, an anti-CLEC2D antibody, as disclosed herein, comprises a combination of heavy chain CDRs 1, 2 and 3, and light chain CDRs 1, 2 and 3, according to the amino acid sequence of the heavy chain CDRs 1, 2 and 3, and light chain CDRs 1, 2 and 3 of anti-CLEC2D antibody No. R1, as disclosed in Table 9A. In some embodiments, an anti-CLEC2D antibody, as disclosed herein, comprises a combination of a heavy chain and a light chain, according to the amino acid sequence of the heavy chain and light chain of anti-CLEC2D antibody No. R1, as disclosed in Table 9A. 
     In some embodiments, an anti-CLEC2D antibody, as disclosed herein, comprises a combination of heavy chain CDRs 1, 2 and 3, and light chain CDRs 1, 2 and 3, according to the amino acid sequence of the heavy chain CDRs 1, 2 and 3, and light chain CDRs 1, 2 and 3 of anti-CLEC2D antibody No. S1, as disclosed in Table 9A. In some embodiments, an anti-CLEC2D antibody, as disclosed herein, comprises a combination of a heavy chain and a light chain, according to the amino acid sequence of the heavy chain and light chain of anti-CLEC2D antibody No. S1, as disclosed in Table 9A. 
     In some embodiments, an anti-CLEC2D antibody, as disclosed herein, comprises a combination of heavy chain CDRs 1, 2 and 3, and light chain CDRs 1, 2 and 3, according to the amino acid sequence of the heavy chain CDRs 1, 2 and 3, and light chain CDRs 1, 2 and 3 of anti-CLEC2D antibody No. T1, as disclosed in Table 9A. In some embodiments, an anti-CLEC2D antibody, as disclosed herein, comprises a combination of a heavy chain and a light chain, according to the amino acid sequence of the heavy chain and light chain of anti-CLEC2D antibody No. T1, as disclosed in Table 9A. 
     In some embodiments, an anti-CLEC2D antibody, as disclosed herein, comprises a combination of heavy chain CDRs 1, 2 and 3, and light chain CDRs 1, 2 and 3, according to the amino acid sequence of the heavy chain CDRs 1, 2 and 3, and light chain CDRs 1, 2 and 3 of anti-CLEC2D antibody No. U1, as disclosed in Table 9A. In some embodiments, an anti-CLEC2D antibody, as disclosed herein, comprises a combination of a heavy chain and a light chain, according to the amino acid sequence of the heavy chain and light chain of anti-CLEC2D antibody No. U1, as disclosed in Table 9A. In some embodiments, the anti-CLEC2D antibody No. U1, as disclosed in Table 9B, comprises a variable heavy chain having a framework region sequence of the Germline gene families: IGHV4, IGHD1 and IGHJ4. In some embodiments, the anti-CLEC2D antibody No. U1, as disclosed in Table 9B, comprises a variable light chain having a framework region sequence of the Germline families: IGKV4 and IGKJ4. 
     In some embodiments, an anti-CLEC2D antibody, as disclosed herein, comprises a combination of heavy chain CDRs 1, 2 and 3, and light chain CDRs 1, 2 and 3, according to the amino acid sequence of the heavy chain CDRs 1, 2 and 3, and light chain CDRs 1, 2 and 3 of anti-CLEC2D antibody No. V1, as disclosed in Table 9A. In some embodiments, an anti-CLEC2D antibody, as disclosed herein, comprises a combination of a heavy chain and a light chain, according to the amino acid sequence of the heavy chain and light chain of anti-CLEC2D antibody No. V1, as disclosed in Table 9A. 
     In some embodiments, an anti-CLEC2D antibody, as disclosed herein, comprises a combination of heavy chain CDRs 1, 2 and 3, and light chain CDRs 1, 2 and 3, according to the amino acid sequence of the heavy chain CDRs 1, 2 and 3, and light chain CDRs 1, 2 and 3 of anti-CLEC2D antibody No. W1, as disclosed in Table 9A. In some embodiments, an anti-CLEC2D antibody, as disclosed herein, comprises a combination of a heavy chain and a light chain, according to the amino acid sequence of the heavy chain and light chain of anti-CLEC2D antibody No. W1, as disclosed in Table 9A. 
     In some embodiments, an anti-CLEC2D antibody, as disclosed herein, comprises a combination of heavy chain CDRs 1, 2 and 3, and light chain CDRs 1, 2 and 3, according to the amino acid sequence of the heavy chain CDRs 1, 2 and 3, and light chain CDRs 1, 2 and 3 of anti-CLEC2D antibody No. X1, as disclosed in Table 9A. In some embodiments, an anti-CLEC2D antibody, as disclosed herein, comprises a combination of a heavy chain and a light chain, according to the amino acid sequence of the heavy chain and light chain of anti-CLEC2D antibody No. X1, as disclosed in Table 9A. 
     In some embodiments, an anti-CLEC2D antibody, as disclosed herein, comprises a combination of heavy chain CDRs 1, 2 and 3, and light chain CDRs 1, 2 and 3, according to the amino acid sequence of the heavy chain CDRs 1, 2 and 3, and light chain CDRs 1, 2 and 3 of anti-CLEC2D antibody No. Y1, as disclosed in Table 9A. In some embodiments, an anti-CLEC2D antibody, as disclosed herein, comprises a combination of a heavy chain and a light chain, according to the amino acid sequence of the heavy chain and light chain of anti-CLEC2D antibody No. Y1, as disclosed in Table 9A. In some embodiments, the anti-CLEC2D antibody No. Y1, as disclosed in Table 9B, comprises a variable heavy chain having a framework region sequence of the Germline gene families: IGHV5, IGHD5 and IGHJ4. In some embodiments, the anti-CLEC2D antibody No. Y1, as disclosed in Table 9B, comprises a variable light chain having a framework region sequence of the Germline families: IGKV3 and IGKJ4. 
     In some embodiments, an anti-CLEC2D antibody, as disclosed herein, comprises a combination of heavy chain CDRs 1, 2 and 3, and light chain CDRs 1, 2 and 3, according to the amino acid sequence of the heavy chain CDRs 1, 2 and 3, and light chain CDRs 1, 2 and 3 of anti-CLEC2D antibody No. Z1, as disclosed in Table 9A. In some embodiments, an anti-CLEC2D antibody, as disclosed herein, comprises a combination of a heavy chain and a light chain, according to the amino acid sequence of the heavy chain and light chain of anti-CLEC2D antibody No. Z1, as disclosed in Table 9A. 
     In some embodiments, an anti-CLEC2D antibody, as disclosed herein, comprises a combination of heavy chain CDRs 1, 2 and 3, and light chain CDRs 1, 2 and 3, according to the amino acid sequence of the heavy chain CDRs 1, 2 and 3, and light chain CDRs 1, 2 and 3 of anti-CLEC2D antibody No. A2, as disclosed in Table 9A. In some embodiments, an anti-CLEC2D antibody, as disclosed herein, comprises a combination of a heavy chain and a light chain, according to the amino acid sequence of the heavy chain and light chain of anti-CLEC2D antibody No. A2, as disclosed in Table 9A. 
     In some embodiments, an anti-CLEC2D antibody, as disclosed herein, comprises a combination of heavy chain CDRs 1, 2 and 3, and light chain CDRs 1, 2 and 3, according to the amino acid sequence of the heavy chain CDRs 1, 2 and 3, and light chain CDRs 1, 2 and 3 of anti-CLEC2D antibody No. B2, as disclosed in Table 9A. In some embodiments, an anti-CLEC2D antibody, as disclosed herein, comprises a combination of a heavy chain and a light chain, according to the amino acid sequence of the heavy chain and light chain of anti-CLEC2D antibody No. B2, as disclosed in Table 9A. 
     In some embodiments, an anti-CLEC2D antibody, as disclosed herein, comprises a combination of heavy chain CDRs 1, 2 and 3, and light chain CDRs 1, 2 and 3, according to the amino acid sequence of the heavy chain CDRs 1, 2 and 3, and light chain CDRs 1, 2 and 3 of anti-CLEC2D antibody No. C2, as disclosed in Table 9A. In some embodiments, an anti-CLEC2D antibody, as disclosed herein, comprises a combination of a heavy chain and a light chain, according to the amino acid sequence of the heavy chain and light chain of anti-CLEC2D antibody No. C2, as disclosed in Table 9A. 
     In some embodiments, an anti-CLEC2D antibody, as disclosed herein, comprises a combination of heavy chain CDRs 1, 2 and 3, and light chain CDRs 1, 2 and 3, according to the amino acid sequence of the heavy chain CDRs 1, 2 and 3, and light chain CDRs 1, 2 and 3 of anti-CLEC2D antibody No. D2, as disclosed in Table 9A. In some embodiments, an anti-CLEC2D antibody, as disclosed herein, comprises a combination of a heavy chain and a light chain, according to the amino acid sequence of the heavy chain and light chain of anti-CLEC2D antibody No. D2, as disclosed in Table 9A. 
     In some embodiments, an anti-CLEC2D antibody, as disclosed herein, comprises a combination of heavy chain CDRs 1, 2 and 3, and light chain CDRs 1, 2 and 3, according to the amino acid sequence of the heavy chain CDRs 1, 2 and 3, and light chain CDRs 1, 2 and 3 of anti-CLEC2D antibody No. E2, as disclosed in Table 9A. In some embodiments, an anti-CLEC2D antibody, as disclosed herein, comprises a combination of a heavy chain and a light chain, according to the amino acid sequence of the heavy chain and light chain of anti-CLEC2D antibody No. E2, as disclosed in Table 9A. In some embodiments, the anti-CLEC2D antibody No. E2, as disclosed in Table 9B, comprises a variable heavy chain having a framework region sequence of the Germline gene families: IGHV1, IGHD5 and IGHJ4. In some embodiments, the anti-CLEC2D antibody No. E2, as disclosed in Table 9B, comprises a variable light chain having a framework region sequence of the Germline families: IGKV1 and IGKJ1. 
     In some embodiments, an anti-CLEC2D antibody, as disclosed herein, comprises a combination of heavy chain CDRs 1, 2 and 3, and light chain CDRs 1, 2 and 3, according to the amino acid sequence of the heavy chain CDRs 1, 2 and 3, and light chain CDRs 1, 2 and 3 of anti-CLEC2D antibody No. F2, as disclosed in Table 9A. In some embodiments, an anti-CLEC2D antibody, as disclosed herein, comprises a combination of a heavy chain and a light chain, according to the amino acid sequence of the heavy chain and light chain of anti-CLEC2D antibody No. F2, as disclosed in Table 9A. 
     In some embodiments, an anti-CLEC2D antibody, as disclosed herein, comprises a combination of heavy chain CDRs 1, 2 and 3, and light chain CDRs 1, 2 and 3, according to the amino acid sequence of the heavy chain CDRs 1, 2 and 3, and light chain CDRs 1, 2 and 3 of anti-CLEC2D antibody No. G2, as disclosed in Table 9A. In some embodiments, an anti-CLEC2D antibody, as disclosed herein, comprises a combination of a heavy chain and a light chain, according to the amino acid sequence of the heavy chain and light chain of anti-CLEC2D antibody No. G2, as disclosed in Table 9A. 
     In some embodiments, an anti-CLEC2D antibody, as disclosed herein, comprises a combination of heavy chain CDRs 1, 2 and 3, and light chain CDRs 1, 2 and 3, according to the amino acid sequence of the heavy chain CDRs 1, 2 and 3, and light chain CDRs 1, 2 and 3 of anti-CLEC2D antibody No. H2, as disclosed in Table 9A. In some embodiments, an anti-CLEC2D antibody, as disclosed herein, comprises a combination of a heavy chain and a light chain, according to the amino acid sequence of the heavy chain and light chain of anti-CLEC2D antibody No. H2, as disclosed in Table 9A. 
     In some embodiments, an anti-CLEC2D antibody, as disclosed herein, comprises a combination of heavy chain CDRs 1, 2 and 3, and light chain CDRs 1, 2 and 3, according to the amino acid sequence of the heavy chain CDRs 1, 2 and 3, and light chain CDRs 1, 2 and 3 of anti-CLEC2D antibody No. I2, as disclosed in Table 9A. In some embodiments, an anti-CLEC2D antibody, as disclosed herein, comprises a combination of a heavy chain and a light chain, according to the amino acid sequence of the heavy chain and light chain of anti-CLEC2D antibody No. I2, as disclosed in Table 9A. In some embodiments, the anti-CLEC2D antibody No. I2, as disclosed in Table 9B, comprises a variable heavy chain having a framework region sequence of the Germline gene families: IGHV6, IGHD1 and IGHJ4. In some embodiments, the anti-CLEC2D antibody No. I2, as disclosed in Table 9B, comprises a variable light chain having a framework region sequence of the Germline families: IGKV3 and IGKJ1. 
     In some embodiments, an anti-CLEC2D antibody, as disclosed herein, comprises a combination of heavy chain CDRs 1, 2 and 3, and light chain CDRs 1, 2 and 3, according to the amino acid sequence of the heavy chain CDRs 1, 2 and 3, and light chain CDRs 1, 2 and 3 of anti-CLEC2D antibody No. J2, as disclosed in Table 9A. In some embodiments, an anti-CLEC2D antibody, as disclosed herein, comprises a combination of a heavy chain and a light chain, according to the amino acid sequence of the heavy chain and light chain of anti-CLEC2D antibody No. J2, as disclosed in Table 9A. 
     In some embodiments, an anti-CLEC2D antibody, as disclosed herein, comprises a combination of heavy chain CDRs 1, 2 and 3, and light chain CDRs 1, 2 and 3, according to the amino acid sequence of the heavy chain CDRs 1, 2 and 3, and light chain CDRs 1, 2 and 3 of anti-CLEC2D antibody No. K2, as disclosed in Table 9A. In some embodiments, an anti-CLEC2D antibody, as disclosed herein, comprises a combination of a heavy chain and a light chain, according to the amino acid sequence of the heavy chain and light chain of anti-CLEC2D antibody No. K2, as disclosed in Table 9A. 
     In some embodiments, an anti-CLEC2D antibody, as disclosed herein, comprises a combination of heavy chain CDRs 1, 2 and 3, and light chain CDRs 1, 2 and 3, according to the amino acid sequence of the heavy chain CDRs 1, 2 and 3, and light chain CDRs 1, 2 and 3 of anti-CLEC2D antibody No. L2, as disclosed in Table 9A. In some embodiments, an anti-CLEC2D antibody, as disclosed herein, comprises a combination of a heavy chain and a light chain, according to the amino acid sequence of the heavy chain and light chain of anti-CLEC2D antibody No. L2, as disclosed in Table 9A. In some embodiments, the anti-CLEC2D antibody No. L2, as disclosed in Table 9B, comprises a variable heavy chain having a framework region sequence of the Germline gene families: IGHV4, IGHD3 and IGHJ4. In some embodiments, the anti-CLEC2D antibody No. L2, as disclosed in Table 9B, comprises a variable light chain having a framework region sequence of the Germline families: IGKV1 and IGKJ3. 
     In some embodiments, an anti-CLEC2D antibody, as disclosed herein, comprises a combination of heavy chain CDRs 1, 2 and 3, and light chain CDRs 1, 2 and 3, according to the amino acid sequence of the heavy chain CDRs 1, 2 and 3, and light chain CDRs 1, 2 and 3 of anti-CLEC2D antibody No. M2, as disclosed in Table 9A. In some embodiments, an anti-CLEC2D antibody, as disclosed herein, comprises a combination of a heavy chain and a light chain, according to the amino acid sequence of the heavy chain and light chain of anti-CLEC2D antibody No. M2, as disclosed in Table 9A. 
     In some embodiments, an anti-CLEC2D antibody, as disclosed herein, comprises a combination of heavy chain CDRs 1, 2 and 3, and light chain CDRs 1, 2 and 3, according to the amino acid sequence of the heavy chain CDRs 1, 2 and 3, and light chain CDRs 1, 2 and 3 of anti-CLEC2D antibody No. N2, as disclosed in Table 9A. In some embodiments, an anti-CLEC2D antibody, as disclosed herein, comprises a combination of a heavy chain and a light chain, according to the amino acid sequence of the heavy chain and light chain of anti-CLEC2D antibody No. N2, as disclosed in Table 9A. 
     In some embodiments, any one or all of the anti-CLEC2D antibodies disclosed herein (e.g., including any one or all of Antibody Nos: A1, B1, E1, P1, U1, Y1, E2, I2 and L2, as disclosed in Table 9A and B) comprise a human IgG1 Fc region or backbone. In some embodiments, any one or all of the anti-CLEC2D antibodies disclosed herein (e.g., including any one or all of Antibody Nos: A1, B1, E1, P1, U1, Y1, E2, I2 and L2, as disclosed in Table 9A and B) comprise a human IgG4 Fc region or backbone. In some embodiments, any one or all of the anti-CLEC2D antibodies disclosed herein (e.g., including any one or all of Antibody Nos: A1, B1, E1, P1, U1, Y1, E2, I2 and L2, as disclosed in Table 9A and B) comprise a human IgG1 N to A Fc region or backbone. In some embodiments, any one or all of the anti-CLEC2D antibodies disclosed herein (e.g., including any one or all of Antibody Nos: A1, B1, E1, P1, U1, Y1, E2, I2 and L2, as disclosed in Table 9A and B) comprise a human IgG2 Fc region or backbone. In some embodiments, any one or all of the anti-CLEC2D antibodies disclosed herein (e.g., including any one or all of Antibody Nos: A1, B1, E1, P1, U1, Y1, E2, I2 and L2, as disclosed in Table 9) is afucosylated. In some embodiments, any one or all of the anti-CLEC2D antibodies disclosed herein (e.g., including any one or all of Antibody Nos: A1, B1, E1, P1, U1, Y1, E2, I2 and L2, as disclosed in Table 9) comprises an afucosylated antibody region. 
     In some embodiments, any one or all of the anti-CLEC2D antibodies selected from the group consisting of Antibody Nos: A1, B1, E1, P1, U1, Y1, E2, I2 and L2, as disclosed in Table 9A and B, comprise a human IgG1 Fc region or backbone. In some embodiments, any one or all of the anti-CLEC2D antibodies selected from the group consisting of Antibody Nos: A1, B1, E1, P1, U1, Y1, E2, I2 and L2, as disclosed in Table 9C, comprise a human IgG4 Fc region or backbone. In some embodiments, any one or all of the anti-CLEC2D antibodies selected from the group consisting of Antibody Nos: A1, B1, E1, P1, U1, Y1, E2, I2 and L2, as disclosed in Table 9A and B, comprise a human IgG1 N to A Fc region or backbone. In some embodiments, any one or all of the anti-CLEC2D antibodies selected from the group consisting of Antibody Nos: A1, B1, E1, P1, U1, Y1, E2, I2 and L2, as disclosed in Table 9C, comprise a human IgG2 Fc region or backbone. 
     In some embodiments, an anti-CLEC2D antibody, as disclosed herein, comprises a combination of a heavy chain and a light chain, according to the amino acid sequence of the heavy chain and light chain of an IgG1 formatted anti-CLEC2D antibody No. A1, as disclosed in Table 9C. 
     In some embodiments, an anti-CLEC2D antibody, as disclosed herein, comprises a combination of a heavy chain and a light chain, according to the amino acid sequence of the heavy chain and light chain of an IgG1 formatted anti-CLEC2D antibody No. B1, as disclosed in Table 9C. 
     In some embodiments, an anti-CLEC2D antibody, as disclosed herein, comprises a combination of a heavy chain and a light chain, according to the amino acid sequence of the heavy chain and light chain of an IgG1 formatted anti-CLEC2D antibody No. E1, as disclosed in Table 9C. 
     In some embodiments, an anti-CLEC2D antibody, as disclosed herein, comprises a combination of a heavy chain and a light chain, according to the amino acid sequence of the heavy chain and light chain of an IgG1 formatted anti-CLEC2D antibody No. P1, as disclosed in Table 9C. 
     In some embodiments, an anti-CLEC2D antibody, as disclosed herein, comprises a combination of a heavy chain and a light chain, according to the amino acid sequence of the heavy chain and light chain of an IgG1 formatted anti-CLEC2D antibody No. U1, as disclosed in Table 9C. 
     In some embodiments, an anti-CLEC2D antibody, as disclosed herein, comprises a combination of a heavy chain and a light chain, according to the amino acid sequence of the heavy chain and light chain of an IgG1 formatted anti-CLEC2D antibody No. Y1, as disclosed in Table 9C. 
     In some embodiments, an anti-CLEC2D antibody, as disclosed herein, comprises a combination of a heavy chain and a light chain, according to the amino acid sequence of the heavy chain and light chain of an IgG1 formatted anti-CLEC2D antibody No. E2, as disclosed in Table 9C. 
     In some embodiments, an anti-CLEC2D antibody, as disclosed herein, comprises a combination of a heavy chain and a light chain, according to the amino acid sequence of the heavy chain and light chain of an IgG1 formatted anti-CLEC2D antibody No. I2, as disclosed in Table 9C. 
     In some embodiments, an anti-CLEC2D antibody, as disclosed herein, comprises a combination of a heavy chain and a light chain, according to the amino acid sequence of the heavy chain and light chain of an IgG1 formatted anti-CLEC2D antibody No. L2, as disclosed in Table 9C. 
     In some embodiments, an anti-CLEC2D antibody, as disclosed herein, comprises a heavy chain, according to the amino acid sequence of the heavy chain of an IgG4 formatted anti-CLEC2D antibody No. A1, as disclosed in Table 9C. 
     In some embodiments, an anti-CLEC2D antibody, as disclosed herein, comprises a heavy chain, according to the amino acid sequence of the heavy chain of an IgG4 formatted anti-CLEC2D antibody No. B1, as disclosed in Table 9C. 
     In some embodiments, an anti-CLEC2D antibody, as disclosed herein, comprises a heavy chain, according to the amino acid sequence of the heavy chain of an IgG4 formatted anti-CLEC2D antibody No. E1, as disclosed in Table 9C. 
     In some embodiments, an anti-CLEC2D antibody, as disclosed herein, comprises a heavy chain, according to the amino acid sequence of the heavy chain of an IgG4 formatted anti-CLEC2D antibody No. P1, as disclosed in Table 9C. 
     In some embodiments, an anti-CLEC2D antibody, as disclosed herein, comprises a heavy chain, according to the amino acid sequence of the heavy chain of an IgG4 formatted anti-CLEC2D antibody No. U1, as disclosed in Table 9C. 
     In some embodiments, an anti-CLEC2D antibody, as disclosed herein, comprises a heavy chain, according to the amino acid sequence of the heavy chain of an IgG4 formatted anti-CLEC2D antibody No. Y1, as disclosed in Table 9C. 
     In some embodiments, an anti-CLEC2D antibody, as disclosed herein, comprises a heavy chain, according to the amino acid sequence of the heavy chain of an IgG4 formatted anti-CLEC2D antibody No. E2, as disclosed in Table 9C. 
     In some embodiments, an anti-CLEC2D antibody, as disclosed herein, comprises a heavy chain, according to the amino acid sequence of the heavy chain of an IgG4 formatted anti-CLEC2D antibody No. I2, as disclosed in Table 9C. 
     In some embodiments, an anti-CLEC2D antibody, as disclosed herein, comprises a heavy chain, according to the amino acid sequence of the heavy chain of an IgG4 formatted anti-CLEC2D antibody No. L2, as disclosed in Table 9C. 
     In some embodiments, an anti-CLEC2D antibody, as disclosed herein, comprises an IgG N2A sequence, according to the amino acid sequence of the heavy chain of an IgG4 formatted anti-CLEC2D antibody No. L2, as disclosed in Table 9C. 
     In some embodiments, an anti-CLEC2D antibody, as disclosed herein, comprises a heavy chain, according to the amino acid sequence of the heavy chain of an IgG2 formatted anti-CLEC2D antibody No. A1, as disclosed in Table 9C. 
     In some embodiments, an anti-CLEC2D antibody, as disclosed herein, comprises a heavy chain, according to the amino acid sequence of the heavy chain of an IgG2 formatted anti-CLEC2D antibody No. B1, as disclosed in Table 9C. 
     In some embodiments, an anti-CLEC2D antibody, as disclosed herein, comprises a heavy chain, according to the amino acid sequence of the heavy chain of an IgG2 formatted anti-CLEC2D antibody No. E1, as disclosed in Table 9C. 
     In some embodiments, an anti-CLEC2D antibody, as disclosed herein, comprises a heavy chain, according to the amino acid sequence of the heavy chain of an IgG2 formatted anti-CLEC2D antibody No. P1, as disclosed in Table 9C. 
     In some embodiments, an anti-CLEC2D antibody, as disclosed herein, comprises a heavy chain, according to the amino acid sequence of the heavy chain of an IgG2 formatted anti-CLEC2D antibody No. U1, as disclosed in Table 9C. 
     In some embodiments, an anti-CLEC2D antibody, as disclosed herein, comprises a heavy chain, according to the amino acid sequence of the heavy chain of an IgG2 formatted anti-CLEC2D antibody No. Y1, as disclosed in Table 9C. 
     In some embodiments, an anti-CLEC2D antibody, as disclosed herein, comprises a heavy chain, according to the amino acid sequence of the heavy chain of an IgG2 formatted anti-CLEC2D antibody No. E2, as disclosed in Table 9C. 
     In some embodiments, an anti-CLEC2D antibody, as disclosed herein, comprises a heavy chain, according to the amino acid sequence of the heavy chain of an IgG2 formatted anti-CLEC2D antibody No. I2, as disclosed in Table 9C. 
     In some embodiments, an anti-CLEC2D antibody, as disclosed herein, comprises a heavy chain, according to the amino acid sequence of the heavy chain of an IgG2 formatted anti-CLEC2D antibody No. L2, as disclosed in Table 9C. 
     In some embodiments, an anti-CLEC2D antibody, as disclosed herein, comprises an IgG N2A sequence, according to the amino acid sequence of the heavy chain of an IgG2 formatted anti-CLEC2D antibody No. L2, as disclosed in Table 9C. 
     In some embodiments, an anti-CLEC2D antibody, as disclosed herein, comprises a heavy chain, according to the amino acid sequence of the heavy chain of an IgG N2A formatted anti-CLEC2D antibody No. A1, as disclosed in Table 9C. 
     In some embodiments, an anti-CLEC2D antibody, as disclosed herein, comprises a heavy chain, according to the amino acid sequence of the heavy chain of an IgG N2A formatted anti-CLEC2D antibody No. B1, as disclosed in Table 9C. 
     In some embodiments, an anti-CLEC2D antibody, as disclosed herein, comprises a heavy chain, according to the amino acid sequence of the heavy chain of an IgG N2A formatted anti-CLEC2D antibody No. E1, as disclosed in Table 9C. 
     In some embodiments, an anti-CLEC2D antibody, as disclosed herein, comprises a heavy chain, according to the amino acid sequence of the heavy chain of an IgG N2A formatted anti-CLEC2D antibody No. P1, as disclosed in Table 9C. 
     In some embodiments, an anti-CLEC2D antibody, as disclosed herein, comprises a heavy chain, according to the amino acid sequence of the heavy chain of an IgG N2A formatted anti-CLEC2D antibody No. U1, as disclosed in Table 9C. 
     In some embodiments, an anti-CLEC2D antibody, as disclosed herein, comprises a heavy chain, according to the amino acid sequence of the heavy chain of an IgG N2A formatted anti-CLEC2D antibody No. Y1, as disclosed in Table 9C. 
     In some embodiments, an anti-CLEC2D antibody, as disclosed herein, comprises a heavy chain, according to the amino acid sequence of the heavy chain of an IgG N2A formatted anti-CLEC2D antibody No. E2, as disclosed in Table 9C. 
     In some embodiments, an anti-CLEC2D antibody, as disclosed herein, comprises a heavy chain, according to the amino acid sequence of the heavy chain of an IgG N2A formatted anti-CLEC2D antibody No. I2, as disclosed in Table 9C. 
     In some embodiments, an anti-CLEC2D antibody, as disclosed herein, comprises a heavy chain, according to the amino acid sequence of the heavy chain of an IgG N2A formatted anti-CLEC2D antibody No. L2, as disclosed in Table 9C. 
     In some embodiments, an anti-CLEC2D antibody, as disclosed herein, comprises an IgG N2A sequence, according to the amino acid sequence of the heavy chain of an IgG N2A formatted anti-CLEC2D antibody No. L2, as disclosed in Table 9C. 
     In some embodiments, any one or all of the anti-CLEC2D antibodies selected from the group consisting of Antibody Nos: A1, B1, E1, P1, U1, Y1, E2, I2 and L2, as disclosed in Table 9A, 9B and 9C, is afucosylated. In some embodiments, any one or all of the anti-CLEC2D antibodies selected from the group consisting of Antibody Nos: A1, B1, E1, P1, U1, Y1, E2, I2 and L2, as disclosed in Table 9A, 9B and 9C, comprises an afucosylated antibody region. 
     In some embodiments, an anti-CLEC2D antibody selected from the group consisting of Antibody Nos: A1, B1, E1, P1, U1, Y1, E2, I2 and L2, as disclosed in Table 9A, 9B and 9C, comprises a variable heavy chain sequence and a variable light chain sequence, that recognizes and binds to a human CLEC2D protein of amino acid sequence according to at least one of SEQ ID NOs: 886-920 and SEQ ID NOs: 930-1003. 
     In some embodiments, an anti-CLEC2D antibody selected from the group consisting of Antibody Nos: A1, B1, E1, P1, U1, Y1, E2, I2 and L2, as disclosed in Table 9A, 9B and 9C, comprises a variable heavy chain sequence and a variable light chain sequence, that recognizes and binds to a human CLEC2D protein of amino acid sequence according to at least one of SEQ ID NOs: 886-909. In some embodiments, an anti-CLEC2D antibody or antibody fragment thereof, as disclosed herein, comprises a variable heavy chain sequence and a variable light chain sequence, that recognizes and binds to a human CLEC2D protein of amino acid sequence according to at least one of SEQ ID NOs: 930-1003. 
     In some embodiments, an anti-CLEC2D antibody selected from the group consisting of Antibody Nos: A1, B1, E1, P1, U1, Y1, E2, I2 and L2, as disclosed in Table 9A, 9B and 9C, comprises a variable heavy chain sequence and a variable light chain sequence, that recognizes and binds to conformational epitope of CLEC2D antigen, comprises of amino acids positions either overlapping and/or non-overlapping with CD161 receptor interacting amino acid residues. 
     In some embodiments, an anti-CLEC2D antibody selected from the group consisting of Antibody Nos: A1, B1, E1, P1, U1, Y1, E2, I2 and L2, as disclosed in Table 9A, 9B and 9C, comprises a variable heavy chain sequence and a variable light chain sequence, that inhibits or abrogates or competes with another antibody that recognizes and binds to conformational epitope of CLEC2D antigen, comprises of amino acids positions either overlapping and/or non-overlapping with CD161 receptor interacting amino acid residues. 
     In some embodiments, an anti-CLEC2D antibody selected from the group consisting of Antibody Nos: A1, B1, E1, P1, U1, Y1, E2, I2 and L2, as disclosed in Table 9A, 9B and 9C, comprises a variable heavy chain sequence and a variable light chain sequence that binds to conformational epitope of CLEC2D antigen comprising of any of the amino acid positions ARG175; TYR177; GLU179; ARG153; ARG84; HIS190; ARG101; GLU150; GLN154; THR152; GLN141; SER105; ASP107; ASP92; THR93; LYS94; LYS144; GLU138; CYS176; GLN139; ARG180; SER187; LYS181; PHE116; ASN95 or a combination thereof. 
     In some embodiments, an anti-CLEC2D antibody selected from the group consisting of Antibody Nos: A1, B1, E1, P1, U1, Y1, E2, I2 and L2, as disclosed in Table 9A, 9B and 9C, comprises a variable heavy chain sequence and a variable light chain sequence that inhibits or abrogates or competes for, the binding of another antibody to conformational epitope of CLEC2D antigen comprising of any of the amino acid positions ARG175; TYR177; GLU179; ARG153; ARG84; HIS190; ARG101; GLU150; GLN154; THR152; GLN141; SER105; ASP107; ASP92; THR93; LYS94; LYS144; GLU138; CYS176; GLN139; ARG180; SER187; LYS181; PHE116; ASN95 or a combination thereof. 
     In some embodiments, an anti-CLEC2D antibody selected from the group consisting of Antibody Nos: A1, B1, E1, P1, U1, Y1, E2, I2 and L2, as disclosed in Table 9A, 9B and 9C, comprises a variable heavy chain sequence and a variable light chain sequence that binds to conformational epitope of CLEC2D antigen, comprises at least one of the amino acids positions ARG175; TYR177; GLU179; ARG153; ARG84; HIS190; ARG101; GLU150; GLN154; THR152; GLN141; SER105; ASP107; ASP92; THR93; LYS94; LYS144; GLU138; CYS176; GLN139; ARG180; SER187; LYS181; PHE116; ASN95 of SEQ ID No: 886-920 and 930-1003, constituting non-linear scaffolds for CD161 receptor interacting amino acid residues, thereby blocking the interaction between CLEC2D and CD161 receptors. 
     In some embodiments, an anti-CLEC2D antibody selected from the group consisting of Antibody Nos: A1, B1, E1, P1, U1, Y1, E2, I2 and L2, as disclosed in Table 9A, 9B and 9C, comprises a variable heavy chain sequence and a variable light chain sequence that binds to conformational epitope of CLEC2D antigen, comprises at least one of the amino acids positions ARG175; TYR177; GLU179; ARG153; ARG84; HIS190; ARG101; GLU150; GLN154; THR152; GLN141; SER105; ASP107; ASP92; THR93; LYS94; LYS144; GLU138; CYS176; GLN139; ARG180; SER187; LYS181; PHE116; ASN95 of SEQ ID No: 886-909 and 930-1003, constituting non-linear scaffolds for CD161 receptor interacting amino acid residues, thereby blocking the interaction between CLEC2D and CD161 receptors. 
     In some embodiments, an anti-CLEC2D antibody selected from the group consisting of Antibody Nos: A1, B1, E1, P1, U1, Y1, E2, I2 and L2, as disclosed in Table 9A, 9B and 9C, comprises a variable heavy chain sequence and a variable light chain sequence that binds to conformational epitope of CLEC2D antigen, comprises at least one of the amino acids positions ARG175; TYR177; GLU179; ARG153; ARG84; HIS190; ARG101; GLU150; GLN154; THR152; GLN141; SER105; ASP107; ASP92; THR93; LYS94; LYS144; GLU138; CYS176; GLN139; ARG180; SER187; LYS181; PHE116; ASN95 of SEQ ID No: 886-890, constituting non-linear scaffolds for CD161 receptor interacting amino acid residues, thereby blocking the interaction between CLEC2D and CD161 receptors. 
     In some embodiments, an anti-CLEC2D antibody selected from the group consisting of Antibody Nos: A1, B1, E1, P1, U1, Y1, E2, I2 and L2, as disclosed in Table 9A, 9B and 9C, comprises a variable heavy chain sequence and a variable light chain sequence that binds to conformational epitope of CLEC2D antigen, comprises at least one of the amino acids positions ARG175; TYR177; GLU179; ARG153; ARG84; HIS190; ARG101; GLU150; GLN154; THR152; GLN141; SER105; ASP107; ASP92; THR93; LYS94; LYS144; GLU138; CYS176; GLN139; ARG180; SER187; LYS181; PHE116; ASN95 of SEQ ID No: 886-920 and 930-1003, constituting allosteric and non-linear scaffolds for CD161 receptor non-interacting amino acid residues, thereby blocking the interaction between CLEC2D and CD161 receptors. 
     In some embodiments, an anti-CLEC2D antibody selected from the group consisting of Antibody Nos: A1, B1, E1, P1, U1, Y1, E2, I2 and L2, as disclosed in Table 9A, 9B and 9C, comprises a variable heavy chain sequence and a variable light chain sequence that binds to conformational epitope of CLEC2D antigen, comprises at least one of the amino acids positions ARG175; TYR177; GLU179; ARG153; ARG84; HIS190; ARG101; GLU150; GLN154; THR152; GLN141; SER105; ASP107; ASP92; THR93; LYS94; LYS144; GLU138; CYS176; GLN139; ARG180; SER187; LYS181; PHE116; ASN95 of SEQ ID No: 886-909 and 930-1003, constituting allosteric and non-linear scaffolds for CD161 receptor non-interacting amino acid residues, thereby blocking the interaction between CLEC2D and CD161 receptors. 
     In some embodiments, an anti-CLEC2D antibody selected from the group consisting of Antibody Nos: A1, B1, E1, P1, U1, Y1, E2, I2 and L2, as disclosed in Table 9A, 9B and 9C, comprises a variable heavy chain sequence and a variable light chain sequence that binds to conformational epitope of CLEC2D antigen, comprises at least one of the amino acids positions ARG175; TYR177; GLU179; ARG153; ARG84; HIS190; ARG101; GLU150; GLN154; THR152; GLN141; SER105; ASP107; ASP92; THR93; LYS94; LYS144; GLU138; CYS176; GLN139; ARG180; SER187; LYS181; PHE116; ASN95 of SEQ ID No: 886-890, constituting allosteric and non-linear scaffolds for CD161 receptor non-interacting amino acid residues, thereby blocking the interaction between CLEC2D and CD161 receptors. 
     In some embodiments, an anti-CLEC2D antibody selected from the group consisting of Antibody Nos: A1, B1, E1, P1, U1, Y1, E2, I2 and L2, as disclosed in Table 9A, 9B and 9C, comprises a variable heavy chain sequence and a variable light chain sequence that when bound to CLEC2D selected from SEQ ID Nos: 886-920 and 930-1003, binds to at least one of the amino acids positions ARG175; TYR177; GLU179; ARG153; ARG84; HIS190; ARG101; GLU150; GLN154; THR152; GLN141; SER105; ASP107; ASP92; THR93; LYS94; LYS144; GLU138; CYS176; GLN139; ARG180; SER187; LYS181; PHE116; ASN95, either independently or in combination to induce tumour killing or cytotoxicity. In some embodiments, an antibody or antigen binding fragment thereof, as disclosed herein, induces cytotoxicity in at least 5%, at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90% or at least 95%, of the total number of cells treated with the antibody or antigen binding fragment thereof. 
     In some embodiments, an anti-CLEC2D antibody selected from the group consisting of Antibody Nos: A1, B1, E1, P1, U1, Y1, E2, I2 and L2, as disclosed in Table 9A, 9B and 9C, comprises a variable heavy chain sequence and a variable light chain sequence that when bound to CLEC2D selected from SEQ ID Nos: 886-909 and 930-1003, binds to at least one of the amino acids positions ARG175; TYR177; GLU179; ARG153; ARG84; HIS190; ARG101; GLU150; GLN154; THR152; GLN141; SER105; ASP107; ASP92; THR93; LYS94; LYS144; GLU138; CYS176; GLN139; ARG180; SER187; LYS181; PHE116; ASN95, either independently or in combination to induce tumour killing or cytotoxicity. In some embodiments, an antibody or antigen binding fragment thereof, as disclosed herein, induces cytotoxicity in at least 5%, at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90% or at least 95%, of the total number of cells treated with the antibody or antigen binding fragment thereof. 
     In some embodiments, an anti-CLEC2D antibody selected from the group consisting of Antibody Nos: A1, B1, E1, P1, U1, Y1, E2, I2 and L2, as disclosed in Table 9A, 9B and 9C, comprises a variable heavy chain sequence and a variable light chain sequence that when bound to CLEC2D selected from SEQ ID Nos: 886-890, binds to at least one of the amino acids positions ARG175; TYR177; GLU179; ARG153; ARG84; HIS190; ARG101; GLU150; GLN154; THR152; GLN141; SER105; ASP107; ASP92; THR93; LYS94; LYS144; GLU138; CYS176; GLN139; ARG180; SER187; LYS181; PHE116; ASN95, either independently or in combination to induce tumour killing or cytotoxicity. In some embodiments, an antibody or antigen binding fragment thereof, as disclosed herein, induces cytotoxicity in at least 5%, at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90% or at least 95%, of the total number of cells treated with the antibody or antigen binding fragment thereof. 
     In some embodiments, an anti-CLEC2D antibody, as disclosed herein is deglycosylated. In some embodiments, a deglycosylated anti-CLEC2D antibody, as disclosed herein exhibits increased cytotoxicity towards a host cell, as compared to a glycosylated form of the same anti-CLEC2D antibody. In some embodiments, an anti-CLEC2D antibody, as disclosed herein comprised an N-linked glycosylation. 
     In some embodiments, an anti-CLEC2D antibody, as disclosed herein is afucosylated. In some embodiments, an afucosylated anti-CLEC2D antibody, as disclosed herein exhibits increased cytotoxicity towards a host cell, as compared to a fucosylated form of the same anti-CLEC2D antibody. 
     In some embodiments, an anti-CLEC2D antibody, as disclosed herein is sialylated. In some embodiments, a sialylated anti-CLEC2D antibody, as disclosed herein exhibits increased cytotoxicity towards a host cell, as compared to an unsialylated form of the same anti-CLEC2D antibody. 
     In some embodiments, an anti-CLEC2D antibody, as disclosed herein is hyper-galactosylated. In some embodiments, a hyper-galactosylated anti-CLEC2D antibody, as disclosed herein exhibits increased cytotoxicity towards a host cell, as compared to an un-galactosylated or low galactosylated form of the same anti-CLEC2D antibody. 
     In some embodiments, an anti-CLEC2D antibody, as disclosed herein is hyper-mannosylated. In some embodiments, a hyper-mannosylated anti-CLEC2D antibody, as disclosed herein exhibits increased cytotoxicity towards a host cell, as compared to a non-galactosylated or low mannosylated form of the same anti-CLEC2D antibody. 
     In some embodiments, the invention as disclosed herein, relates to a nucleic acid sequence encoding the amino acid sequence of the heavy chain CDRs 1, 2 and 3 of any of the anti-CLEC2D antibodies, as disclosed herein. In some embodiments, the invention as disclosed herein, relates to a nucleic acid sequence encoding the amino acid sequence of the light chain CDRs 1, 2 and 3 of any of the anti-CLEC2D antibodies, as disclosed herein. 
     In some embodiments, the invention as disclosed herein, relates to a nucleic acid sequence encoding the amino acid sequence of the variable heavy chain of any of the anti-CLEC2D antibodies, as disclosed herein. In some embodiments, the invention as disclosed herein, relates to a nucleic acid sequence encoding the amino acid sequence of the light chain of any of the anti-CLEC2D antibodies, as disclosed herein. 
     In some embodiments, the invention as disclosed herein, relates to a nucleic acid sequence encoding the amino acid sequence of the variable heavy chain CDRs 1, 2 and 3 of any of the anti-CLEC2D antibodies, as disclosed in Table 9A. In some embodiments, the invention as disclosed herein, relates to a nucleic acid sequence encoding the amino acid sequence of the variable light chain CDRs 1, 2 and 3 of any of the anti-CLEC2D antibodies, as disclosed in Table 9A. 
     In some embodiments, the invention as disclosed herein, relates to a nucleic acid sequence encoding the amino acid sequence of the variable heavy chain any of the anti-CLEC2D antibodies, as disclosed in Table 9A. In some embodiments, the invention as disclosed herein, relates to a nucleic acid sequence encoding the amino acid sequence of the variable light chain of any of the anti-CLEC2D antibodies, as disclosed in Table 9A. 
     In some embodiments, the invention as disclosed herein, relates to a nucleic acid sequence encoding the amino acid sequence of the variable heavy chain CDRs 1, 2 and 3 of any of the anti-CLEC2D antibodies, as disclosed in Table 9A. In some embodiments, the invention as disclosed herein, relates to a nucleic acid sequence encoding the amino acid sequence of the variable heavy chain of any of the anti-CLEC2D antibodies, as disclosed in Table 9A. 
     In some embodiments, the invention as disclosed herein, relates to a nucleic acid sequence encoding the amino acid sequence of the variable light chain CDRs 1, 2 and 3 of any of the anti-CLEC2D antibodies, as disclosed in Table 9A. In some embodiments, the invention as disclosed herein, relates to a nucleic acid sequence encoding the amino acid sequence of the variable light chain of any of the anti-CLEC2D antibodies, as disclosed in Table 9A. 
     In some embodiments, the invention as disclosed herein, relates to a nucleic acid sequence encoding the amino acid sequence of the heavy chain of the anti-CLEC2D antibodies, as disclosed in Table 9A, having a framework region sequence of the Germline families as disclosed herein. In some embodiments, the invention as disclosed herein, relates to a nucleic acid sequence encoding the amino acid sequence of the light chain of the anti-CLEC2D antibodies, as disclosed in Table 9A, having a framework region sequence of the Germline families as disclosed herein. 
     In some embodiments, the anti-CLEC2D antibody or antibody fragment thereof, as disclosed herein, can comprise a framework region sequence that is derived from or is a human, a murine, a rodent, a lagomorph, an equine, a bovine, an avian, a caprine, a porcine, a piscean, a canine or a feline framework germline family. In some embodiments, the anti-CLEC2D antibody or antibody fragment thereof, as disclosed herein, can comprise a framework region sequence that is derived from or is a human framework germline family. 
     In some embodiments, the invention as disclosed herein, relates to a vector carrying the nucleic acid encoding the amino acid sequences of an anti-CLEC2D antibody, as disclosed herein. In some embodiments, the invention as disclosed herein, relates to a vector carrying any one or all of the nucleic acid sequences encoding the amino acid sequences of an anti-CLEC2D antibody, as disclosed in Table 9A. 
     In some embodiments, the invention as disclosed herein, relates to a host cell transfected with a vector carrying the nucleic acid encoding the amino acid sequences of an anti-CLEC2D antibody, as disclosed herein. In some embodiments, the invention as disclosed herein, relates to relates to a host cell transfected with a vector carrying the nucleic acid sequences encoding the amino acid sequences of an anti-CLEC2D antibody, as disclosed in Table 9A. 
     In some embodiments, the anti-CLEC2D antibodies or antibody fragments thereof, as disclosed herein, can be conjugated to an agent, a chemical or a small molecule. In some embodiments, the agent is a therapeutic agent. In some embodiments, the therapeutic agent is a chemotherapeutic drug. In some embodiments, the therapeutic agent is a cytotoxic agent or drug. In some embodiments, the therapeutic agent is a radioisotope. In some embodiments, the agent is a diagnostic agent. In some embodiments, the diagnostic agent includes but is not limited to a fluorescent, chemiluminescent or radioisotopic dye or agent. 
     Epitope Recognition 
     Generally, the term “epitope” refers to the area or region on an antigen to which an antibody specifically binds, i.e., it is the area or region in physical contact with the antibody. A protein epitope may comprise amino acid residues in the antigen that are directly involved in binding to an antibody (also called the immunodominant component of the epitope) and other amino acid residues, which are not directly involved in the binding. In some embodiments, the term epitope herein includes both types of binding sites of any particular region of CLEC2D that specifically binds to an anti-CLEC2D antibody, or another CLEC2D-specific agent according to this disclosure, unless otherwise stated (e.g., in some contexts this disclosure relates to antibodies that bind directly to particular amino acid residues). More detailed epitope mapping of specific anti-CLEC2D antibody could be determined through an alanine scan approach. 
     In some embodiments, an anti-CLEC2D antibody or antibody fragment thereof, as disclosed herein, comprises a variable heavy chain sequence and a variable light chain sequence, that recognizes and binds to a human CLEC2D protein of amino acid sequence according to at least one of SEQ ID NOs: 886 to 920 and 930-1003. 
     In some embodiments, an anti-CLEC2D antibody or antibody fragment thereof, as disclosed herein, comprises a variable heavy chain sequence and a variable light chain sequence, that recognizes and binds to a human CLEC2D protein of amino acid sequence according to at least one of SEQ ID NOs: 886 to 909. In some embodiments, an anti-CLEC2D antibody or antibody fragment thereof, as disclosed herein, comprises a variable heavy chain sequence and a variable light chain sequence, that recognizes and binds to a human CLEC2D protein of amino acid sequence according to at least one of SEQ ID NOs: 930 to 1003. 
     In some embodiments, an anti-CLEC2D antibody or antibody fragment thereof, as disclosed herein, comprises a variable heavy chain sequence and a variable light chain sequence, that recognizes and binds to conformational epitope of CLEC2D antigen, comprises of amino acids positions either overlapping and/or non-overlapping with CD161 receptor interacting amino acid residues. 
     In some embodiments, an anti-CLEC2D antibody or antibody fragment thereof, as disclosed herein, comprises a variable heavy chain sequence and a variable light chain sequence, that inhibits or abrogates or competes with another antibody that recognizes and binds to conformational epitope of CLEC2D antigen, comprises of amino acids positions either overlapping and/or non-overlapping with CD161 receptor interacting amino acid residues. 
     In some embodiments, an antibody or antigen binding fragment thereof, as disclosed herein, comprises a variable heavy chain sequence and a variable light chain sequence that binds to conformational epitope of CLEC2D antigen comprising of any of the amino acid positions ARG175; TYR177; GLU179; ARG153; ARG84; HIS190; ARG101; GLU150; GLN154; THR152; GLN141; SER105; ASP107; ASP92; THR93; LYS94; LYS144; GLU138; CYS176; GLN139; ARG180; SER187; LYS181; PHE116; ASN95 or a combination thereof. 
     In some embodiments, an antibody or antigen binding fragment thereof, as disclosed herein, comprises a variable heavy chain sequence and a variable light chain sequence that inhibits or abrogates or competes for, the binding of another antibody to conformational epitope of CLEC2D antigen comprising of any of the amino acid positions ARG175; TYR177; GLU179; ARG153; ARG84; HIS190; ARG101; GLU150; GLN154; THR152; GLN141; SER105; ASP107; ASP92; THR93; LYS94; LYS144; GLU138; CYS176; GLN139; ARG180; SER187; LYS181; PHE116; ASN95 or a combination thereof. 
     In some embodiments, an antibody or antigen binding fragment thereof, as disclosed herein, comprises a variable heavy chain sequence and a variable light chain sequence that binds to conformational epitope of CLEC2D antigen, comprises at least one of the amino acids positions ARG175; TYR177; GLU179; ARG153; ARG84; HIS190; ARG101; GLU150; GLN154; THR152; GLN141; SER105; ASP107; ASP92; THR93; LYS94; LYS144; GLU138; CYS176; GLN139; ARG180; SER187; LYS181; PHE116; ASN95 of SEQ ID No: 886-920 and 930-1003, constituting non-linear scaffolds for CD161 receptor interacting amino acid residues, thereby blocking the interaction between CLEC2D and CD161 receptors. 
     In some embodiments, an antibody or antigen binding fragment thereof, as disclosed herein, comprises a variable heavy chain sequence and a variable light chain sequence that binds to conformational epitope of CLEC2D antigen, comprises at least one of the amino acids positions ARG175; TYR177; GLU179; ARG153; ARG84; HIS190; ARG101; GLU150; GLN154; THR152; GLN141; SER105; ASP107; ASP92; THR93; LYS94; LYS144; GLU138; CYS176; GLN139; ARG180; SER187; LYS181; PHE116; ASN95 of SEQ ID No: 886-909 and 930-1003, constituting non-linear scaffolds for CD161 receptor interacting amino acid residues, thereby blocking the interaction between CLEC2D and CD161 receptors. 
     In some embodiments, an antibody or antigen binding fragment thereof, as disclosed herein, comprises a variable heavy chain sequence and a variable light chain sequence that binds to conformational epitope of CLEC2D antigen, comprises at least one of the amino acids positions ARG175; TYR177; GLU179; ARG153; ARG84; HIS190; ARG101; GLU150; GLN154; THR152; GLN141; SER105; ASP107; ASP92; THR93; LYS94; LYS144; GLU138; CYS176; GLN139; ARG180; SER187; LYS181; PHE116; ASN95 of SEQ ID No: 886-890, constituting non-linear scaffolds for CD161 receptor interacting amino acid residues, thereby blocking the interaction between CLEC2D and CD161 receptors. 
     In some embodiments, an antibody or antigen binding fragment thereof, as disclosed herein, comprises a variable heavy chain sequence and a variable light chain sequence that binds to conformational epitope of CLEC2D antigen, comprises at least one of the amino acids positions ARG175; TYR177; GLU179; ARG153; ARG84; HIS190; ARG101; GLU150; GLN154; THR152; GLN141; SER105; ASP107; ASP92; THR93; LYS94; LYS144; GLU138; CYS176; GLN139; ARG180; SER187; LYS181; PHE116; ASN95 of SEQ ID No: 886-920 and 930-1003, constituting allosteric and non-linear scaffolds for CD161 receptor non-interacting amino acid residues, thereby blocking the interaction between CLEC2D and CD161 receptors. 
     In some embodiments, an antibody or antigen binding fragment thereof, as disclosed herein, comprises a variable heavy chain sequence and a variable light chain sequence that binds to conformational epitope of CLEC2D antigen, comprises at least one of the amino acids positions ARG175; TYR177; GLU179; ARG153; ARG84; HIS190; ARG101; GLU150; GLN154; THR152; GLN141; SER105; ASP107; ASP92; THR93; LYS94; LYS144; GLU138; CYS176; GLN139; ARG180; SER187; LYS181; PHE116; ASN95 of SEQ ID No: 886-909 and 930-1003, constituting allosteric and non-linear scaffolds for CD161 receptor non-interacting amino acid residues, thereby blocking the interaction between CLEC2D and CD161 receptors. 
     In some embodiments, an antibody or antigen binding fragment thereof, as disclosed herein, comprises a variable heavy chain sequence and a variable light chain sequence that binds to conformational epitope of CLEC2D antigen, comprises at least one of the amino acids positions ARG175; TYR177; GLU179; ARG153; ARG84; HIS190; ARG101; GLU150; GLN154; THR152; GLN141; SER105; ASP107; ASP92; THR93; LYS94; LYS144; GLU138; CYS176; GLN139; ARG180; SER187; LYS181; PHE116; ASN95 of SEQ ID No: 886-890, constituting allosteric and non-linear scaffolds for CD161 receptor non-interacting amino acid residues, thereby blocking the interaction between CLEC2D and CD161 receptors. 
     In some embodiments, an antibody or antigen binding fragment thereof, as disclosed herein, comprises a variable heavy chain sequence and a variable light chain sequence that when bound to CLEC2D selected from SEQ ID Nos: 886-920 and 930-1003 binds to at least one of the amino acids positions ARG175; TYR177; GLU179; ARG153; ARG84; HIS190; ARG101; GLU150; GLN154; THR152; GLN141; SER105; ASP107; ASP92; THR93; LYS94; LYS144; GLU138; CYS176; GLN139; ARG180; SER187; LYS181; PHE116; ASN95, either independently or in combination to induce tumour killing or cytotoxicity. In some embodiments, an antibody or antigen binding fragment thereof, as disclosed herein, induces cytotoxicity in at least 5%, at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90% or at least 95%, of the total number of cells treated with the antibody or antigen binding fragment thereof 
     In some embodiments, an antibody or antigen binding fragment thereof, as disclosed herein, comprises a variable heavy chain sequence and a variable light chain sequence that when bound to CLEC2D selected from SEQ ID Nos: 886-909 and 930-1003 binds to at least one of the amino acids positions ARG175; TYR177; GLU179; ARG153; ARG84; HIS190; ARG101; GLU150; GLN154; THR152; GLN141; SER105; ASP107; ASP92; THR93; LYS94; LYS144; GLU138; CYS176; GLN139; ARG180; SER187; LYS181; PHE116; ASN95, either independently or in combination to induce tumour killing or cytotoxicity. In some embodiments, an antibody or antigen binding fragment thereof, as disclosed herein, induces cytotoxicity in at least 5%, at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90% or at least 95%, of the total number of cells treated with the antibody or antigen binding fragment thereof. 
     In some embodiments, an antibody or antigen binding fragment thereof, as disclosed herein, comprises a variable heavy chain sequence and a variable light chain sequence that when bound to CLEC2D selected from SEQ ID Nos: 886-890 binds to at least one of the amino acids positions ARG175; TYR177; GLU179; ARG153; ARG84; HIS190; ARG101; GLU150; GLN154; THR152; GLN141; SER105; ASP107; ASP92; THR93; LYS94; LYS144; GLU138; CYS176; GLN139; ARG180; SER187; LYS181; PHE116; ASN95, either independently or in combination to induce tumour killing or cytotoxicity. In some embodiments, an antibody or antigen binding fragment thereof, as disclosed herein, induces cytotoxicity in at least 5%, at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90% or at least 95%, of the total number of cells treated with the antibody or antigen binding fragment thereof. 
     In some embodiments, an anti-CLEC2D antibody as disclosed herein, comprises a variable heavy chain sequence and a variable light chain sequence, that recognizes and binds to the amino acid residues: THR178; ASN95; ARG137; GLU179; TYR177; SER98; GLU162; GLN139; ARG101; ALA160; TRP96; CYS176; GLU138; ARG175; GLY140; SER136; ASP104; ASP92; THR97; LYS94; GLU150; THR149; GLY148; GLN141; PRO142; LYS144; THR152; TRP151; ASN147; ARG153; TRP143; ILE157; CYS163; SER129; THR93; LYS181; ASP91; ARG180; SER187; LYS194; TYR165; ALA174; LEU110; ASN167; ASP168; ILE146; SER172; GLY161; SER173; LEU135; ASP130; GLN100; PHE155; GLY159; PRO156; LEU158; GLN117; SER115; GLU114; GLN154; ASN120; PHE116; PHE102; GLN106; SER105; ASP107; LYS186; ASP109; GLN112; VAL191; TRP145; LYS169; GLY127; PRO128; GLN83; LYS85; GLU77; GLY170; LEU119; LEU123; TRP182; SER90; ALA108; TYR88; HIS190; ILE189; ALA73; ARG84; SER78; TRP79; PRO76; PHE82; ALA171; ASP188; CYS75 within a human CLEC2D of amino acid sequence according to SEQ ID NOs: 886, 889, 894, 899, 903, 905, 906 or 907. 
     In some embodiments, an anti-CLEC2D antibody as disclosed herein, comprises a variable heavy chain sequence and a variable light chain sequence, that recognizes and binds to the amino acid residues: ARG175; TYR177; GLU179; ARG153; ARG84; HIS190; ARG101; GLU150; GLN154; THR152; GLN141; SER105; ASP107; ASP92; THR93; LYS94; LYS144; GLU138; CYS176; GLN139; ARG180; SER187; LYS181; PHE116; ASN95, within a human CLEC2D of amino acid sequence according to SEQ ID NOs: 886, 889, 894, 899, 903, 905, 906 or 907. 
     In some embodiments, an anti-CLEC2D antibody or antibody fragment thereof, as disclosed herein, comprises a variable heavy chain sequence and a variable light chain sequence of SEQ ID 42 &amp; SEQ ID 258, that recognizes and binds to a human CLEC2D protein of amino acid sequence according to at least one of SEQ ID NOs: 886 to 909. In some embodiments, an anti-CLEC2D antibody or antibody fragment thereof, as disclosed herein, comprises a variable heavy chain sequence and a variable light chain sequence of SEQ ID 42 &amp; SEQ ID 258, that recognizes and binds to a human CLEC2D protein of amino acid sequence according to at least one of SEQ ID NOs: 921 to 909. 
     In some embodiments, an anti-CLEC2D antibody or antibody fragment thereof, as disclosed herein, comprises a variable heavy chain sequence and a variable light chain sequence, that recognizes and binds to conformational epitope of CLEC2D antigen, comprises of amino acids positions either overlapping and/or non-overlapping with CD161 receptor interacting amino acid residues. 
     In some embodiments, an anti-CLEC2D antibody or antibody fragment thereof, as disclosed herein, comprises a variable heavy chain sequence and a variable light chain sequence, that inhibits or abrogates or competes with another antibody that recognizes and binds to conformational epitope of CLEC2D antigen, and comprises of amino acids positions either overlapping and/or non-overlapping with CD161 receptor interacting amino acid residues. 
     In some embodiments, an antibody or antigen binding fragment thereof, as disclosed herein, comprises a variable heavy chain sequence and a variable light chain sequence that binds to conformational epitope of CLEC2D antigen comprising of any of the amino acid positions ARG175; TYR177; GLU179; ARG153; ARG84; HIS190; ARG101; GLU150; GLN154; THR152; GLN141; SER105; ASP107; ASP92; THR93; LYS94; LYS144; GLU138; CYS176; GLN139; ARG180; SER187; LYS181; PHE116; ASN95 or a combination thereof. 
     In some embodiments, an antibody or antigen binding fragment thereof, as disclosed herein, comprises a variable heavy chain sequence and a variable light chain sequence that inhibits or abrogates or competes with, the binding of another antibody to conformational epitope of CLEC2D antigen comprising of any of the amino acid positions ARG175; TYR177; GLU179; ARG153; ARG84; HIS190; ARG101; GLU150; GLN154; THR152; GLN141; SER105; ASP107; ASP92; THR93; LYS94; LYS144; GLU138; CYS176; GLN139; ARG180; SER187; LYS181; PHE116; ASN95 or a combination thereof. 
     In some embodiments, an antibody or antigen binding fragment thereof, as disclosed herein, comprises a variable heavy chain sequence and a variable light chain sequence that binds to conformational epitope of CLEC2D antigen, comprises at least one of the amino acids positions ARG175; TYR177; GLU179; ARG153; ARG84; HIS190; ARG101; GLU150; GLN154; THR152; GLN141; SER105; ASP107; ASP92; THR93; LYS94; LYS144; GLU138; CYS176; GLN139; ARG180; SER187; LYS181; PHE116; ASN95 of SEQ ID No: 886-920 and 930-1003, constituting non-linear scaffolds for CD161 receptor interacting amino acid residues, thereby blocking the interaction between CLEC2D and CD161 receptors. 
     In some embodiments, an antibody or antigen binding fragment thereof, as disclosed herein, comprises a variable heavy chain sequence and a variable light chain sequence that binds to conformational epitope of CLEC2D antigen, comprises at least one of the amino acids positions ARG175; TYR177; GLU179; ARG153; ARG84; HIS190; ARG101; GLU150; GLN154; THR152; GLN141; SER105; ASP107; ASP92; THR93; LYS94; LYS144; GLU138; CYS176; GLN139; ARG180; SER187; LYS181; PHE116; ASN95 of SEQ ID No: 886-909 and 930-1003, constituting non-linear scaffolds for CD161 receptor interacting amino acid residues, thereby blocking the interaction between CLEC2D and CD161 receptors. 
     In some embodiments, an antibody or antigen binding fragment thereof, as disclosed herein, comprises a variable heavy chain sequence and a variable light chain sequence that binds to conformational epitope of CLEC2D antigen, comprises at least one of the amino acids positions ARG175; TYR177; GLU179; ARG153; ARG84; HIS190; ARG101; GLU150; GLN154; THR152; GLN141; SER105; ASP107; ASP92; THR93; LYS94; LYS144; GLU138; CYS176; GLN139; ARG180; SER187; LYS181; PHE116; ASN95 of SEQ ID No: 886-890, constituting non-linear scaffolds for CD161 receptor interacting amino acid residues, thereby blocking the interaction between CLEC2D and CD161 receptors. 
     In some embodiments, an antibody or antigen binding fragment thereof, as disclosed herein, comprises a variable heavy chain sequence and a variable light chain sequence that binds to conformational epitope of CLEC2D antigen, comprises at least one of the amino acids positions ARG175; TYR177; GLU179; ARG153; ARG84; HIS190; ARG101; GLU150; GLN154; THR152; GLN141; SER105; ASP107; ASP92; THR93; LYS94; LYS144; GLU138; CYS176; GLN139; ARG180; SER187; LYS181; PHE116; ASN95 of SEQ ID No: 886-920 and 930-1003, constituting allosteric and non-linear scaffolds for CD161 receptor non-interacting amino acid residues, thereby blocking the interaction between CLEC2D and CD161 receptors. 
     In some embodiments, an antibody or antigen binding fragment thereof, as disclosed herein, comprises a variable heavy chain sequence and a variable light chain sequence that binds to conformational epitope of CLEC2D antigen, comprises at least one of the amino acids positions ARG175; TYR177; GLU179; ARG153; ARG84; HIS190; ARG101; GLU150; GLN154; THR152; GLN141; SER105; ASP107; ASP92; THR93; LYS94; LYS144; GLU138; CYS176; GLN139; ARG180; SER187; LYS181; PHE116; ASN95 of SEQ ID No: 886-909 and 930-1003, constituting allosteric and non-linear scaffolds for CD161 receptor non-interacting amino acid residues, thereby blocking the interaction between CLEC2D and CD161 receptors. 
     In some embodiments, an antibody or antigen binding fragment thereof, as disclosed herein, comprises a variable heavy chain sequence and a variable light chain sequence that binds to conformational epitope of CLEC2D antigen, comprises at least one of the amino acids positions ARG175; TYR177; GLU179; ARG153; ARG84; HIS190; ARG101; GLU150; GLN154; THR152; GLN141; SER105; ASP107; ASP92; THR93; LYS94; LYS144; GLU138; CYS176; GLN139; ARG180; SER187; LYS181; PHE116; ASN95 of SEQ ID No: 886-890, constituting allosteric and non-linear scaffolds for CD161 receptor non-interacting amino acid residues, thereby blocking the interaction between CLEC2D and CD161 receptors. 
     In some embodiments, an antibody or antigen binding fragment thereof, as disclosed herein, comprises a variable heavy chain sequence and a variable light chain sequence that when bound to CLEC2D selected from SEQ ID Nos: 886-920 and 930-1003, binds to at least one of the amino acids positions ARG175; TYR177; GLU179; ARG153; ARG84; HIS190; ARG101; GLU150; GLN154; THR152; GLN141; SER105; ASP107; ASP92; THR93; LYS94; LYS144; GLU138; CYS176; GLN139; ARG180; SER187; LYS181; PHE116; ASN95, either independently or in combination to induce tumor killing or cytotoxicity. In some embodiments, an antibody or antigen binding fragment thereof, as disclosed herein, induces cytotoxicity in at least 5%, at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90% or at least 95%, of the total number of cells treated with the antibody or antigen binding fragment thereof. 
     In some embodiments, an antibody or antigen binding fragment thereof, as disclosed herein, comprises a variable heavy chain sequence and a variable light chain sequence that when bound to CLEC2D selected from SEQ ID Nos: 886-909 and 930-1003, binds to at least one of the amino acids positions ARG175; TYR177; GLU179; ARG153; ARG84; HIS190; ARG101; GLU150; GLN154; THR152; GLN141; SER105; ASP107; ASP92; THR93; LYS94; LYS144; GLU138; CYS176; GLN139; ARG180; SER187; LYS181; PHE116; ASN95, either independently or in combination to induce tumor killing or cytotoxicity. In some embodiments, an antibody or antigen binding fragment thereof, as disclosed herein, induces cytotoxicity in at least 5%, at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90% or at least 95%, of the total number of cells treated with the antibody or antigen binding fragment thereof. 
     In some embodiments, an antibody or antigen binding fragment thereof, as disclosed herein, comprises a variable heavy chain sequence and a variable light chain sequence that when bound to CLEC2D selected from SEQ ID Nos: 886-890, binds to at least one of the amino acids positions ARG175; TYR177; GLU179; ARG153; ARG84; HIS190; ARG101; GLU150; GLN154; THR152; GLN141; SER105; ASP107; ASP92; THR93; LYS94; LYS144; GLU138; CYS176; GLN139; ARG180; SER187; LYS181; PHE116; ASN95, either independently or in combination to induce tumor killing or cytotoxicity. In some embodiments, an antibody or antigen binding fragment thereof, as disclosed herein, induces cytotoxicity in at least 5%, at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90% or at least 95%, of the total number of cells treated with the antibody or antigen binding fragment thereof. 
     In some embodiments, an anti-CLEC2D antibody, SEQ ID 42 &amp; SEQ ID 258, as disclosed herein, comprises a variable heavy chain sequence and a variable light chain sequence, that recognizes and binds to the amino acid ARG175-XAA176-TYR177-XAA178-GLU179; ARG153; ARG84; HIS190. 
     In some embodiments, an anti-CLEC2D antibody, SEQ ID 44 &amp; SEQ ID 260, as disclosed herein, comprises a variable heavy chain sequence and a variable light chain sequence, that recognizes and binds to the amino acid ARG101; GLU150-XAA151-THR152-ARG153-GLN154; ARG175-XAA176-TYR177-XAA178-GLU179. 
     In some embodiments, an anti-CLEC2D antibody, SEQ ID 45 &amp; SEQ ID 261, as disclosed herein, comprises a variable heavy chain sequence and a variable light chain sequence, that recognizes and binds to the amino acid GLN141; ARG101-XAA102-XAA-103-XAA104-SER105-XAA106-ASP107; HIS190. 
     In some embodiments, an anti-CLEC2D antibody, SEQ ID 1 &amp; SEQ ID 217, as disclosed herein, comprises a variable heavy chain sequence and a variable light chain sequence, that recognizes and binds to the amino acids GLN141; ARG153; ASP92-THR93-LYS94; HIS190. 
     In some embodiments, an anti-CLEC2D antibody SEQ ID 58 &amp; SEQ ID 274, as disclosed herein, comprises a variable heavy chain sequence and a variable light chain sequence, that recognizes and binds to the amino acids GLU138-XAA139-XAA140-GLN141-XAA142-XAA143-LYS144; CYS176. 
     In some embodiments, an anti-CLEC2D antibody, SEQ ID 35 &amp; SEQ ID 251, as disclosed herein, comprises a variable heavy chain sequence and a variable light chain sequence, that recognizes and binds to the amino acids GLU138-GLN139-XAA140-GLN141; ARG175-XAA176-TYR177-XAA178-XAA179-ARG180; SER187. 
     In some embodiments, an anti-CLEC2D antibody SEQ ID 21 &amp; SEQ ID 237, as disclosed herein, comprises a variable heavy chain sequence and a variable light chain sequence that recognizes and binds to the amino acids ASP92; TYR177-XAA179-XAA180-LYS181; THR152-ARG153-GLN154. 
     In some embodiments, an anti-CLEC2D antibody, SEQ ID 7 &amp; SEQ ID 223, as disclosed herein, comprises a variable heavy chain sequence and a variable light chain sequence, that recognizes and binds to the amino acids THR93-XAA94-ASN95; ARG101; GLN139; PHE116; ARG153. 
     In some embodiments, an anti-CLEC2D antibody, SEQ ID 73 &amp; SEQ ID 289, as disclosed herein, comprises a variable heavy chain sequence and a variable light chain sequence, that recognizes and binds to the amino acids THR93-LYS94; ARG101; GLN141; TYR177-XAA178-GLU179. 
     In some embodiments, an anti-CLEC2D antibody, SEQ ID 73 &amp; SEQ ID 289, as disclosed herein, comprises a variable heavy chain sequence and a variable light chain sequence, that recognizes and binds to any one of the amino acids according to SEQ ID NOs: 2561-2567. 
     In some embodiments, an anti-CLEC2D antibody, SEQ ID 73 &amp; SEQ ID 289, as disclosed herein, comprises a variable heavy chain sequence and a variable light chain sequence, that recognizes and binds to the amino acids according to SEQ ID NO: 2561. 
     In some embodiments, an anti-CLEC2D antibody, SEQ ID 73 &amp; SEQ ID 289, as disclosed herein, comprises a variable heavy chain sequence and a variable light chain sequence, that recognizes and binds to the amino acids according to SEQ ID NO: 2562. 
     In some embodiments, an anti-CLEC2D antibody, SEQ ID 73 &amp; SEQ ID 289, as disclosed herein, comprises a variable heavy chain sequence and a variable light chain sequence, that recognizes and binds to the amino acids according to SEQ ID NO: 2563. 
     In some embodiments, an anti-CLEC2D antibody, SEQ ID 73 &amp; SEQ ID 289, as disclosed herein, comprises a variable heavy chain sequence and a variable light chain sequence, that recognizes and binds to the amino acids according to SEQ ID NO: 2564. 
     In some embodiments, an anti-CLEC2D antibody, SEQ ID 73 &amp; SEQ ID 289, as disclosed herein, comprises a variable heavy chain sequence and a variable light chain sequence, that recognizes and binds to the amino acids according to SEQ ID NO: 2565. 
     In some embodiments, an anti-CLEC2D antibody, SEQ ID 73 &amp; SEQ ID 289, as disclosed herein, comprises a variable heavy chain sequence and a variable light chain sequence, that recognizes and binds to the amino acids according to SEQ ID NO: 2566. 
     In some embodiments, an anti-CLEC2D antibody, SEQ ID 73 &amp; SEQ ID 289, as disclosed herein, comprises a variable heavy chain sequence and a variable light chain sequence, that recognizes and binds to the amino acids according to SEQ ID NO: 2567. 
     Library Screening 
     Without wishing to be bound by any particular technique, antibodies which bind to the antigens of the disclosure can be identified and characterized using the methods described below. 
     Provided herein is a naïve antibody library as a source of therapeutics for treatment of diseases comprising cancers, rheumatoid arthritis, neurological disorders, infectious diseases and metabolic disorders or any combination thereof. Antibodies identified using the methods of the disclosure can be used as diagnostic tools, as prognostic tools; for research purposes, for target discovery, for validation in functional genomics or any application where antibodies or derivatives of antibodies are employed. 
     In one embodiment, the term “panning” refers to an affinity selection technique which selects for binders against a specific target/antigen. 
     In some embodiments, methods of screening the naïve antibody gene expression library include sequentially exploring the expression profiles of a pool of gene clones by utilizing two separate scanning tools: 1) a phage display technology, and 2) a yeast display technology (FIG. 3). Use of yeast system for antibody gene expression is advantageous because of the eukaryotic protein translation, processing and proper folding of the antibody products on the cell surface. Further, yeast expression allows proper interaction with antigenic targets with high specificity. 
     In some embodiments, the methods disclosed herein preserve the diversity in the library that is capable of identifying unique molecules against varied antigenic targets. 
     In some embodiments of the methods of the disclosure, the methodology also involves a strategy wherein the diversity is translated between two platforms and explored as various engineered antibody formats including, but not limited to, chimeric antibody molecules, Fv, Fav, F(ab′)2, Fab′, dsFv, scFv, sc(Fv)2, scFv-CH3, scFv-Fc, ScFab, dimeric and trimeric antibody fragments, minibodies, humanized monoclonal antibody molecules, human antibodies, bispecific antibodies, fusion proteins comprising an Fc region of an antibody, and any functional fragments arising out of these molecules wherein the derivative molecules retain the immunological functionality of the parent antibody molecule, and all other antibody formats. 
     In some embodiments, the candidate antibody molecules obtained by the present method are further optimized through rational design guided by structure-function studies of antibody-antigen interactions. The prerequisite for success of manufacturability of monoclonal antibody drugs are dependent on a variety of biological and/or correlated properties such as solubility, aggregation, antigenicity, stability and so on. As exemplified, structure-based drug design, which is rational, evidence based and faster, has contributed tremendously to the field of cancer chemotherapy, drug resistant infections, neurological diseases, amongst others. The resulting outcome of these methods is employed in the instant disclosure to improve antibody library construction and manufacturability of selected molecules. 
     In some embodiments, the term “isolated” relates to novel and unique molecules comprising of two protein chains or fragments thereof which are not part of a biological membrane. In particular, the isolated molecule according to the current disclosure is soluble and is linked either directly or indirectly via linker molecules through covalent or non-covalent bonds. These molecules may comprise monoclonal or polyclonal antibodies, which can be easily obtained according to methods well-known to the man skilled in the art. 
     In some embodiments, an affinity tag may be included in an antigen or antibody disclosed herein for isolation or detection purposes. Affinity tags are well known in the art and are attached to a target and used to detect or isolate the target using a molecule that binds the affinity tag. In principal, any peptide or protein for which an antibody or other specific binding agent is available can be used as an affinity tag. Exemplary affinity tags suitable for use include, but are not limited to, a monocytic adaptor protein (MONA) binding peptide, a T7 binding peptide, a v5 tag, a streptavidin binding peptide, a polyhistidine tract, protein A (Nilsson et al., EMBO J. 4:1075 (1985); Nilsson et al., Methods Enzymol. 198:3 (1991)), glutathione S transferase (Smith and Johnson, Gene 67:31 (1988)), Glu-Glu affinity tag (Grussenmeyer et al., Proc. Natl. Acad. Sci. USA 82:7952 (1985)), substance P, FLAG peptide (Hopp et al., Biotechnology 6:1204 (1988)), or other antigenic epitope or binding domain. See, in general, Ford et al., Protein Expression and Purification 2:95 (1991). In one embodiment, a His6 tag is used in the methods disclosed herein. In another embodiment, a FLAG tag is used in the methods disclosed herein. In another embodiment, a v5 tag is used in the methods and compositions disclosed herein. DNA molecules encoding affinity tags are available from commercial suppliers (e.g., Pharmacia Biotech, Piscataway, N.J.). 
     Taken together, the methods of the present disclosure are centralized around identifying, validating, characterizing and developing novel monoclonal antibodies against CLEC2D antigenic target. These novel monoclonal antibodies are developed for use in therapeutics, diagnostics and prognostics products applicable in various diseases, including cancers. 
     In some embodiments, the antibody library, which can be a naïve antibody library, allows for isolation of unique antibody molecules with the desired functional properties for a specific therapeutic target. i.e., an antigen such as the CLEC2D protein or any fragments thereof disclosed herein. 
     The combination of a diverse library and an appropriate and compatible display platform enables the rapid selection and production of therapeutic antibodies with higher affinity and improved functionality against specific antigen molecule. Typical screening for targeted therapeutic antibody molecules comprises selecting molecules from a diverse and large antibody library against a target antigen through display platforms via smaller antibody fragments followed by constructing a full-length antibody molecule expressed in a mammalian cell line. Once expressed, the process of purification and several functional assays to validate the same are performed. Optimization of parameters such as identification of epitopes, formulation, stability studies and in vivo efficacy further strengthen the development of the selected lead antibodies. 
     In an exemplary embodiment of the present disclosure, the method of screening, isolation and development of monoclonal antibodies from the human naïve antibody library against CLEC2D antigen comprises the following description. Designing and generation of various CLEC2D antigen constructs, i.e., soluble ecto-domain of wild-type and mutants; full-length CLEC2D proteins, in appropriately optimized/customized vectors to express in mammalian system followed by purification through affinity chromatography methods to homogeneity. 
     In some embodiments, the screening of a library of molecules is performed by about 1 to 3 rounds of phage panning with a CLEC2D antigen. During each round, specific binders are selected out from the library by removing non-binders. Selected pools of molecules screened in the phage display platform are transferred, with or without randomization of selected diversity, to a yeast surface display platform. This avoids any PCR based method steps, thereby preserving the selected pool of molecules against the CLEC2D antigen. The yeast display platform comprises expressing a variety of antibody moieties in different formats. Displayed fragments are screened against specific antigenic targets and specific populations showing higher affinity to the target antigen are separated. These selected pools are further tested for antigen specificity. Finally, individual clones are separated and clonal populations are used for sequencing of individual antibody clones. 
     Methods of phage panning against antigens are known in the art. For example, magnetic beads can be used. Antigen coated on magnetic dynabeads can be prepared, and a phage antibody library panned against the antigen coated beads to separate phage particles expressing the desired antibody clones. 
     Purified DNA can then be digested and ligated into a suitable yeast expression vector to generate antibodies in the desired format, such as Fab or ScFv. Yeast cells can be transformed by standard methods and checked for antibody expression. The surface expression of antibodies can be analysed with multiple tags such as FLAG, c-Myc and (His) 6 -tag and V5-tag for heavy chains and light chains, respectively and immunohistochemistry. Flow cytometry can be used to isolate yeast cells expressing antibody sequences showing specific antigen binding. Flow cytometry sorting of yeast cell populations can be repeated at least 1×, at least 2×, at least 3×, at least 4× or at least 5× to enrich for antibody clones with higher affinity towards labelled antigens. 
     Individual yeast clones are sequences using methods standard in the art, and the antibody sequences are further cloned into suitable mammalian gene expression vectors. 
     The disclosure provides methods of screening a high diversity antibody gene library for antibodies that bind to a CLEC2D antigen. In some embodiments, the methods comprise inserting a library of antibody genes into a phage protein gene in a vector, and transforming phages to produce a phage library comprising the high diversity antibody gene library. The phages in the phage library display the library of antibody genes on the surface of the phage. This phage library is then panned with a CLEC2D antigen for individual phages that bind to the CLEC2D antigen, thereby producing an enriched phage library that is enriched for antibody genes that encode antibodies that bind to the CLEC2D antigen. This panning can be accomplished, for example, by conjugating the antigen to magnetic beads, which can be used to isolated phages that bind to the antigen on the beads. The panning step can be repeated at least once, at least twice or more times to enrich for phages expressing antibodies or antibody fragments that bind to the antigen. 
     Antibody or antibody fragment genes from the enriched phage library are then transferred to a yeast surface display library. In some embodiments, this is accomplished by cloning the antibody or antibody fragment genes into a suitable yeast transformation vector, and transforming yeast cells with methods that are standard in the art. Yeast cells that express antibody or antibody fragments that bind that bind to the CLEC2D antigen are then isolated. In some embodiments, this isolation is accomplished using flow cytometry to sort the yeast cells. In some embodiments, the method further comprises repeating the flow cytometry isolation at least 1×, at least 2×, at least 3×, at least 4× or at least 5× or more times to enrich for yeast cells expressing antibodies or antibody fragments that bind the antigen. In some embodiments, the methods further comprise analyzing the surface expression of the antibody genes with a FLAG tag, a c-Myc tag, a polyhistidine tag or a V5 tag. In some embodiments, the method further comprises cloning the antibody genes that bind to CLEC2D into a mammalian expression vector. 
     Optimization and Purification 
     In some embodiments, the methods disclosed herein comprise the design, generation and optimization of vector constructs for smooth transfer of selected antibody gene sequences to mammalian cell lines such as Chinese hamster ovary (CHO) cell lines for expression, stable cell-line generation and subsequent purification of full-length monoclonal antibody. This allows the rapid and efficient establishment of stable cell lines expressing monoclonal antibodies with excellent homogeneity in terms of conformation and posttranslational modification that are seen in downstream processes. 
     All cell lines suitable for the expression and purification of antibodies or antibody fragments are considered to be within the scope of the disclosure. In some embodiments, the cell line is a mammalian cell line. Cell lines can be isolated or derived from any source, including human, mouse and hamster. Suitable cell lines include, but are not limited to, Chinese Hamster Ovary (CHO) cells, HEK 293 cells, HEK293T cells, BHK21 cells, NSO cells, PER.C6 cells, B cells, HEK 293-6E cells, Sp2/0-Ag14 cells and DG44 cells. 
     In some embodiments, the CDR lengths and the amino acid composition of antibody clones is analyzed to understand the novelty of these clones. Additional careful analysis is performed to eliminate clones that have motifs with detrimental to physico-chemical properties that have a direct impact on purification strategy, stability, and charge variants present or within the antibodies. 
     In some embodiments, the scale up of lead antibody clones is achieved through defined culture media, supplements, and specific bioreactor processes which are known in the art and described herein. 
     Exemplary purification methods of the disclosure comprise multiple steps of chromatography techniques that utilize the exploiting physico-chemical nature of the amino acid composition in antibody molecules. In addition, higher purity can be attained by effectively removing the host cell protein/impurities, polymer (or aggregate), of the antibody and improving the antibody recovery rate. Purification of antibody molecules is concluded with appropriate formulation which will further improve the stability. 
     Therapeutic compositions comprise of conditions that are sterile and stable under the conditions of manufacture and storage. 
     Antibody purification processes will be known to those of skill in the art. Without wishing to be bound by any particular process, exemplary antibody purification processes comprise centrifugation of a primary cell culture expressing the antibody or antibody fragment to be purified, followed by further clarification using a filter such as a 3 μm-30 μm filter. Subsequently, collected filtrate can be further filtered, for example through 0.22 μm filters. This sample can be loaded onto a column for further purification by liquid chromatography. Exemplary columns include, but are not limited to, XK 16/20 Protein A Columns. Liquid chromatography can include treatment with a high salt wash buffer to remove loosely bound host cell proteins and other impurities. A low pH wash buffer can remove traces of impurities. Subsequently, bound protein can be eluted using 30 mM Phosphate buffer at pH.3.0-4.0. This sample can be diluted to reduce the conductivity, and then can be further purified using anion exchange (AEX) Chromatography in a flow through mode (i.e., using negative binding). An exemplary AEX column includes, but is not limited to, a Q Sepharose XK 16/20 column, which can be pre-equilibrated in 10-100 mM Histidine and/or citrate and/or phosphate and/or MES and/or acetate buffer (pH 4.5-6.5). Weakly interacting proteins can be removed using an elution buffer as a wash, and bound proteins such as the antibodies or antibody fragments of the disclosure are eluted, for example, in a single step using elution buffer containing 1 M NaCl and/or KCl. Flow through from AEX Chromatography can be loaded onto a pre-equilibrated apto SP ImpRes C10/20 column in 10-100 mM Histidine and/or citrate and/or phosphate and/or 2-(N-morpholino)ethanesulfonic acid (MES) and/or Acetate buffer (pH 4.5-6.5). Bound proteins such as antibodies or antibody fragments of the disclosure can be eluted through step elution followed by gradient elution using elution buffer (Equilibration buffer containing 200-1000 mM NaCl and/or KCl, pH 4.5-6.5). However, high salt buffer containing 1 to 1.5 M NaCl, pH 4.5-6.5, can be to remove strongly bound proteins, if present. 
     Taken together, antibodies and antibody fragments of the disclosure can be purified through multiple steps of chromatography techniques in order to achieve high purity, while effectively removing the host cell protein/impurities, polymer (or aggregate), of the antibody and improving the antibody recovery rate; Exemplary chromatography methods include the use of a mixed mode resin having both an ion exchange group and a hydrophobic functional group. Amino acids can be used as an additive. 
     Methods of Treatment 
     As used herein. “treating” or “treat” describes the management and care of a patient for the purpose of combating a disease, condition, or disorder and includes the administration of an antibody or pharmaceutical composition comprising same of the disclosure to alleviate one or more symptoms or complications of a disease, condition or disorder, or to eliminate the disease, condition or disorder. The term “treat” can also include treatment of a cell in vitro or an animal model. 
     An antibody of the present disclosure, or a pharmaceutical composition thereof, can also be used to prevent a disease, condition or disorder, or used to identify suitable candidates for such purposes. As used herein, “preventing” or “prevent” describes reducing or eliminating the onset of the symptoms or complications of the disease, condition or disorder. 
     As used herein, the term “alleviate” is meant to describe a process by which the severity of a sign or symptom of a disorder is decreased. Importantly, a sign or symptom can be alleviated without being eliminated. In a preferred embodiment, the administration of pharmaceutical compositions of this disclosure leads to the elimination of a sign or symptom, however, elimination is not required. Effective dosages are expected to decrease the severity of a sign or symptom. For instance, a sign or symptom of a disorder such as cancer, which can occur in multiple locations, is alleviated if the severity of the cancer is decreased within at least one of multiple locations. 
     As used herein the term “symptom” is defined as an indication of disease, illness, injury, or that something is not right in the body. Symptoms are felt or noticed by the individual experiencing the symptom, but may not easily be noticed by others. Others are defined as non-health-care professionals. 
     As used herein the term “sign” is also defined as an indication that something is not right in the body. But signs are defined as things that can be seen by a doctor, nurse, or other health care professional. 
     A therapeutically effective amount of an antibody of the disclosure relates generally to the amount needed to achieve a therapeutic objective. As noted above, this may be a binding interaction between the antibody and its target antigen that, in certain cases, interferes with the functioning of the target. The amount required to be administered will furthermore depend on the binding affinity of the antibody for its specific antigen, and will also depend on the rate at which an administered antibody is depleted from the free volume other subject to which it is administered. Common ranges for therapeutically effective dosing of an antibody or antibody fragment of the disclosure may be, by way of nonlimiting example, from about 0.1 mg/kg body weight to about 50 mg/kg body weight. Common dosing frequencies may range, for example, from twice daily to once a week. 
     Where antibody fragments are used, the smallest inhibitory fragment that specifically binds to the binding domain of the target protein is preferred. For example, based upon the variable-region sequences of an antibody, peptide molecules can be designed that retain the ability to bind the target protein sequence. Such peptides can be synthesized chemically and/or produced by recombinant DNA technology. (See, e.g., Marasco et al., Proc. Natl. Acad. Sci. USA, 90: 7889-7893 (1993)). 
     In a non-limiting embodiment of the disclosure, isolated monoclonal antibodies reveal differential expression of CLEC2D on various cell surfaces, including immune cells and tumor cells, in response to various inducing conditions. This indicates the use of anti-CLEC2D antibodies as therapeutic agents for multiple disease indications. 
     The disclosure provides methods of treating diseases by modulating or inhibiting the interaction of CLEC2D with its cognate receptor CD161 by administering the compositions, the antibodies or antigen binding fragments thereof, and/or nucleic acids encoding the antibodies or antigen binding fragments thereof of the disclosure to a subject in need thereof. 
     In some embodiments, the diseases treated by the compositions, antibodies or antigen binding fragments thereof, and/or nucleic acids encoding the antibodies or antigen binding fragments thereof of the disclosure is a cancer, an autoimmune disease, an inflammatory disease, an infectious disease, or other diseases in which CLEC2D plays a role (e.g., by inhibiting CD161) in the initiation and/or development of the disease. 
     Exemplary diseases include, but are not limited to seronegative spondyloarthropathies such as psoriatic arthritis, ankylosing spondylitis, reiters syndrome and spondyloarthropathy associated with inflammatory bowel disease. 
     Exemplary diseases include, but are not limited to prosthetic joint loosening. 
     Exemplary diseases include, but are not limited to connective tissue diseases such as juvenile rheumatoid arthritis, rheumatoid arthritis, systemic lupus erythematosus (SLE) and lupus nephritis, scleroderma, Sjogren&#39;s syndrome, mixed connective tissue disease and polymyositis, dermatomyositis. 
     Exemplary diseases include, but are not limited to inflammatory bowel diseases such as Crohn&#39;s disease and ulcerative colitis. 
     Exemplary diseases include, but are not limited to Whipples disease and arthritis associated with granulomatous ileocolitis. 
     Exemplary diseases include, but are not limited to inflammatory skin conditions such as autoimmune bullous pemphigoid, autoimmune pemphigus vulgaris, eczema and dermatitis. 
     Exemplary diseases include, but are not limited to inflammatory lung diseases such as alveolitis, pulmonary fibrosis, sarcoidoisis, asthma, bronchitis and bronchiolitis obliterans. 
     Exemplary diseases include, but are not limited to inflammatory renal diseases such as glomerulonethritis, renal allograft rejection and renal tubular inflammation. 
     Exemplary diseases include, but are not limited to atherosclerosis. 
     Exemplary diseases include, but are not limited to systemic vasculitis such as temporal arteritis/giant cell arteritis, takayasu arteritis, polyarteritis nodosa, Kawasaki disease, Wegener&#39;s granulomatosis, churg strauss syndrome, microscopic polyangiitis, necrotising glomerulonephritis, henoch schonlein purpura, essential cryoglobulinaemic vasculitis, other small vessel vasculitis and Behcets disease 
     Exemplary diseases include, but are not limited to macrophage activation diseases such as macrophage activation syndrome (MAS), adult onset stills disease and haemophagocytic syndrome. 
     Exemplary diseases include, but are not limited to polymyalgia rheumatica, primary biliary sclerosis, sclerosing cholangitis, autoimmune hepatitis, Type 1 Diabetes Mellitus, Hashimoto&#39;s thyroiditis, Graves&#39; disease, multiple sclerosis (MS), Guillain-Barre syndrome, Addison&#39;s disease, and/or Raynaud&#39;s phenomenon and Goodpasture&#39;s syndrome. 
     Exemplary diseases include, but are not limited to diseases linked with cancers and cancers, which comprise breast cancer, prostate cancer, endometrial cancer, uterine cancer, bladder cancer, kidney cancer, esophageal cancer, squamous cell carcinoma, uveal melanoma, glioma, glioblastoma, myeloma, pheochromocytoma, paraganglioma, follicular lymphoma, renal cell carcinoma, cendcal cancer, ovarian cancer, cervical cancer, lung cancer, colorectal cancer, brain cancer, pancreatic cancer, gastric cancer, intestinal cancer, testicular cancer, skin cancer, thyroid cancer, thymoma, head and neck cancer, liver cancer, pharynx cancer, adrenocortical cancer, cholangiocarcinoma, mesothelioma, sarcoma, leukemia, lymphoma, Hodgkin&#39;s disease, multiple myeloma, melanoma, astrocytoma, stomach cancer, pulmonary adenocarcinoma, adenocarcinoma, acinic cell adenocarcinoma, adrenal cortical carcinomas, alveoli cell carcinoma, anaplastic carcinoma, basaloid carcinoma, basal cell carcinoma, bronchiolar carcinoma, bronchogenic carcinoma, renaladinol carcinoma, embryonal carcinoma, anometroid carcinoma, fibrolamolar liver cell carcinoma, follicular carcinomas, giant cell carcinomas, hepatocellular carcinoma, intraepidermal carcinoma, intraepithelial carcinoma, leptomanigio carcinoma, medullary carcinoma, melanotic carcinoma, menigual carcinoma, mesometonephric carcinoma, oat cell carcinoma, squamal cell carcinoma, sweat gland carcinoma, transitional cell carcinoma, tubular cell carcinoma, ameloblastic sarcoma, angiolithic sarcoma, botryoid sarcoma, endometrial stroma sarcoma, ewing sarcoma, fascicular sarcoma, giant cell sarcoma, granulositic sarcoma, immunoblastic sarcoma, juxaccordial osteogenic sarcoma, coppices sarcoma, leukocytic sarcoma (leukemia), lymphatic sarcoma (lympho sarcoma), medullary sarcoma, myeloid sarcoma (granulocitic sarcoma), austiogenci sarcoma, periosteal sarcoma, reticulum cell sarcoma (histiocytic lymphoma), round cell sarcoma, spindle cell sarcoma, synovial sarcoma, telangiectatic audiogenic sarcoma, Burkitt&#39;s lymphoma, NPDL, NML, NH, diffuse lymphomas, Hodgkin&#39;s lymphoma, non-Hodgkin&#39;s lymphoma, B-cell lymphoma, T-cell lymphoma, diffuse large B-cell lymphoma, acute myeloid lymphoma, chronic lymphocytic leukemia, chronic myeoloid leukemia, mantle cell lymphoma, and follicular lymphoma. 
     Exemplary diseases include, but are not limited to Adrenocortical Carcinoma, Bladder Urothelial Carcinoma, Breast Invasive Carcinoma, Cervical Squamous Cell Carcinoma and Endocervical Adenocarcinoma, Cholangiocarcinoma, Colon Adenocarcinoma, Lymphoid Neoplasm Diffuse Large B-cell Lymphoma, Esophageal Carcinoma, Glioblastoma Multiforme, Head and Neck Squamous Cell Carcinoma, Kidney Chromophobe, Kidney Renal Clear Cell Carcinoma, Kidney Renal Papillary Cell Carcinoma, Acute Myeloid Leukemia, Brain Lower Grade Glioma, Liver Hepatocellular Carcinoma, Lung Adenocarcinoma, Lung Squamous Cell Carcinoma, Mesothelioma, Ovarian Serous Cystadenocarcinoma, Pancreatic Adenocarcinoma, Pheochromocytoma and Paraganglioma, Prostate Adenocarcinoma, Rectum Adenocarcinoma, Sarcoma, Skin Cutaneous Melanoma, Stomach Adenocarcinoma, Testicular Germ Cell Tumors, Thyroid Carcinoma, Thymoma, Uterine Corpus Endometrial Carcinoma, Uterine Carcinosarcoma, and Uveal Melanoma. 
     According to a preferred embodiment, the compositions and methods of this disclosure are directed to the treatment of metastatic cancer to bone, wherein the metastatic cancer is breast, lung, renal, multiple myeloma, thyroid, prostate, adenocarcinoma, blood cell malignancies, including leukemia and lymphoma; head and neck cancers; gastrointestinal cancers, including esophageal cancer, stomach cancer, colon cancer, intestinal cancer, colorectal cancer, rectal cancer, pancreatic cancer, liver cancer, pharynx cancer, cancer of the bile duct or gall bladder; malignancies of the female genital tract, including ovarian carcinoma, uterine endometrial cancers, vaginal cancer, and cervical cancer; bladder cancer; brain cancer, including neuroblastoma; sarcoma, osteosarcoma; and skin cancer, including malignant melanoma or squamous cell cancer. 
     In some embodiments, the methods of treatment of a disease or disorder in a subject, as disclosed herein, relates to activation of an immune cell in the subject in need thereof. In some embodiments, the methods of treatment of a disease or disorder in a subject, as disclosed herein, relates to activation of an immune cell (e.g., NK cell, B-cell, or T-cell). In some embodiments, the methods of treatment of a disease or disorder in a subject, as disclosed herein, relates to treatment of a mammalian subject. In some embodiments, the methods of treatment of a disease or disorder in a subject, as disclosed herein, relates to treatment of a human subject. 
     In some embodiments, the anti-CLEC2D antibodies or a composition comprising the anti-CLEC2D antibodies of the disclosure, are used as a therapeutic agents for treatment of a disease or disorder, in a subject in need thereof. 
     In some embodiments, the anti-CLEC2D antibodies or a composition comprising the anti-CLEC2D antibodies of the disclosure, are used as a therapeutic agents for treatment of a disease or disorder associated with differential or aberrant expression of CLEC2D on various cell surfaces, in a subject in need thereof. 
     In some embodiments, the anti-CLEC2D antibodies or a composition comprising the anti-CLEC2D antibodies of the disclosure, are used as a therapeutic agents for treatment of a disease or disorder associated with differential or aberrant expression of CLEC2D on various cell surfaces, in a subject in need thereof, wherein the cells are immune cells or tumor cells. 
     In some embodiments, the anti-CLEC2D antibodies or a composition comprising the anti-CLEC2D antibodies of the disclosure, are used as a therapeutic agents for treatment of a disease or disorder associated with differential or aberrant expression of CLEC2D in various cell surfaces, in a subject in need thereof wherein the anti-CLEC2D antibodies or a composition comprising the anti-CLEC2D antibodies are administered to the subject in an amount effective for modulating or inhibiting the interaction of CLEC2D with its cognate receptor CD161. 
     In some embodiments, the anti-CLEC2D antibodies or a composition comprising the anti-CLEC2D antibodies of the disclosure, are used as a therapeutic agents for treatment of a disease or disorder associated with differential or aberrant expression of CLEC2D in various cell surfaces, in a subject in need thereof, wherein the anti-CLEC2D antibodies or a composition comprising the anti-CLEC2D antibodies are administered to the subject in an amount effective for binding to and activating NK cells. 
     In some embodiments, the anti-CLEC2D antibodies or a composition comprising the anti-CLEC2D antibodies of the disclosure, are used as a therapeutic agents for treatment of a disease or disorder associated with differential or aberrant expression of CLEC2D, in a subject in need thereof, wherein the method comprises administering the anti-CLEC2D antibodies or a composition comprising the anti-CLEC2D antibodies in an amount effective for treatment or alleviating the symptoms of the disease in the subject. In some embodiments, the anti-CLEC2D antibodies or a composition comprising the anti-CLEC2D antibodies of the disclosure, used in a method of treating a disease or disorder associated with differential or aberrant expression of CLEC2D, in a subject in need thereof, modulate or inhibit the interaction of CLEC2D with its cognate receptor CD161. 
     In some embodiments, the anti-CLEC2D antibodies or a composition comprising the anti-CLEC2D antibodies of the disclosure, are used in a method of treating a disease or disorder including; but not limited to seronegative spondyloarthropathies such as psoriatic arthritis, ankylosing spondylitis, reiters syndrome and spondyloarthropathy associated with inflammatory bowel disease, in a subject in need thereof, wherein the method comprises administering the anti-CLEC2D antibodies or a composition comprising the anti-CLEC2D antibodies in an amount effective for treatment or alleviating the symptoms of the disease in the subject. 
     In some embodiments, the anti-CLEC2D antibodies or a composition comprising the anti-CLEC2D antibodies of the disclosure, are used in a method of treating a disease or disorder including but not limited to connective tissue diseases such as juvenile rheumatoid arthritis, rheumatoid arthritis, systemic lupus erythematosus (SLE) and lupus nephritis, scleroderma, Sjogren&#39;s syndrome, mixed connective tissue disease and polymyositis, dermatomyositis, in a subject in need thereof, wherein the method comprises administering the anti-CLEC2D antibodies or a composition comprising the anti-CLEC2D antibodies in an amount effective for treatment or alleviating the symptoms of the disease in the subject. 
     In some embodiments, the anti-CLEC2D antibodies or a composition comprising the anti-CLEC2D antibodies of the disclosure, are used in a method of treating a disease or disorder including but not limited to connective tissue diseases such as juvenile rheumatoid arthritis, rheumatoid arthritis, systemic lupus erythematosus (SLE) and lupus nephritis, scleroderma, Sjogren&#39;s syndrome, mixed connective tissue disease and polymyositis, dermatomyositis, in a subject in need thereof, wherein the method comprises administering the anti-CLEC2D antibodies or a composition comprising the anti-CLEC2D antibodies in an amount effective for treatment or alleviating the symptoms of the disease in the subject. 
     In some embodiments, the anti-CLEC2D antibodies or a composition comprising the anti-CLEC2D antibodies of the disclosure, are used in a method of treating a disease or disorder including; but not limited to connective tissue diseases such as juvenile rheumatoid arthritis, rheumatoid arthritis, systemic lupus erythematosus (SLE) and lupus nephritis, scleroderma, Sjogren&#39;s syndrome, mixed connective tissue disease and polymyositis, dermatomyositis, in a subject in need thereof, wherein the method comprises administering the anti-CLEC2D antibodies or a composition comprising the anti-CLEC2D antibodies in an amount effective for treatment or alleviating the symptoms of the disease in the subject. 
     In some embodiments, the anti-CLEC2D antibodies or a composition comprising the anti-CLEC2D antibodies of the disclosure, are used in a method of treating a disease or disorder including; but not limited to connective tissue diseases such as inflammatory bowel diseases such as Crohn&#39;s disease and ulcerative colitis, in a subject in need thereof, wherein the method comprises administering the anti-CLEC2D antibodies or a composition comprising the anti-CLEC2D antibodies in an amount effective for treatment or alleviating the symptoms of the disease in the subject. 
     In some embodiments, the anti-CLEC22) antibodies or a composition comprising the anti-CLEC2D antibodies of the disclosure, are used in a method of treating a disease or disorder including but not limited to connective tissue diseases such as Whipples disease and arthritis associated with granulomatous ileocolitis, in a subject in need thereof, wherein the method comprises administering the anti-CLEC2D antibodies or a composition comprising the anti-CLEC2D antibodies in an amount effective for treatment or alleviating the symptoms of the disease in the subject. 
     In some embodiments, the anti-CLEC2D antibodies or a composition comprising the anti-CLEC2D antibodies of the disclosure, are used in a method of treating a disease or disorder including but not limited to inflammatory skin conditions such as autoimmune bullous pemphigoid, autoimmune pemphigus vulgaris, eczema and dermatitis, in a subject in need thereof, wherein the method comprises administering the anti-CLEC2D antibodies or a composition comprising the anti-CLEC2D antibodies in an amount effective for treatment or alleviating the symptoms of the disease in the subject. 
     In some embodiments, the anti-CLEC2D antibodies or a composition comprising the anti-CLEC2D antibodies of the disclosure, are used in a method of treating a disease or disorder including but not limited to inflammatory lung diseases such as alveolitis, pulmonary fibrosis, sarcoidoisis, asthma, bronchitis and bronchiolitis obliterans, in a subject in need thereof, wherein the method comprises administering the anti-CLEC2D antibodies or a composition comprising the anti-CLEC2D antibodies in an amount effective for treatment or alleviating the symptoms of the disease in the subject. 
     In some embodiments, the anti-CLEC2D antibodies or a composition comprising the anti-CLEC2D antibodies of the disclosure, are used in a method of treating a disease or disorder including but not limited to atherosclerosis and coronary vascular diseases in a subject in need thereof, wherein the method comprises administering the anti-CLEC2D antibodies or a composition comprising the anti-CLEC2D antibodies in an amount effective for treatment or alleviating the symptoms of the disease in the subject. 
     In some embodiments, the anti-CLEC2D antibodies or a composition comprising the anti-CLEC2D antibodies of the disclosure, are used in a method of treating a disease or disorder including but not limited to inflammatory renal diseases such as glomerulonethritis, renal allograft rejection and renal tubular inflammation, in a subject in need thereof, wherein the method comprises administering the anti-CLEC2D antibodies or a composition comprising the anti-CLEC2D antibodies in an amount effective for treatment or alleviating the symptoms of the disease in the subject. 
     In some embodiments, the anti-CLEC2D antibodies or a composition comprising the anti-CLEC2D antibodies of the disclosure, are used in a method of treating a disease or disorder including but not limited to systemic vasculitis such as temporal arteritis/giant cell arteritis, takayasu arteritis, polyarteritis nodosa, Kawasaki disease, Wegener&#39;s granulomatosis, churg strauss syndrome, microscopic polyangiitis, necrotising glomerulonephritis, henoch schonlein purpura, essential cryoglobulinaemic vasculitis, other small vessel vasculitis and Behcets disease, in a subject in need thereof, wherein the method comprises administering the anti-CLEC2D antibodies or a composition comprising the anti-CLEC2D antibodies in an amount effective for treatment or alleviating the symptoms of the disease in the subject. 
     In some embodiments, the anti-CLEC2D antibodies or a composition comprising the anti-CLEC2D antibodies of the disclosure, are used in a method of treating a disease or disorder including but not limited to systemic vasculitis such as temporal arteritis/giant cell arteritis, takayasu arteritis, polyarteritis nodosa, Kawasaki disease, Wegener&#39;s granulomatosis, churg strauss syndrome, microscopic polyangiitis, necrotising glomerulonephritis, henoch schonlein purpura, essential cryoglobulinaemic vasculitis, other small vessel vasculitis and Behcets disease, in a subject in need thereof, wherein the method comprises administering the anti-CLEC2D antibodies or a composition comprising the anti-CLEC2D antibodies in an amount effective for treatment or alleviating the symptoms of the disease in the subject. 
     In some embodiments, the anti-CLEC2D antibodies or a composition comprising the anti-CLEC2D antibodies of the disclosure, are used in a method of treating a disease or disorder including but not limited to macrophage activation diseases such as macrophage activation syndrome (MAS), adult onset stills disease and haemophagocytic syndrome, in a subject in need thereof, wherein the method comprises administering the anti-CLEC2D antibodies or a composition comprising the anti-CLEC2D antibodies in an amount effective for treatment or alleviating the symptoms of the disease in the subject. 
     In some embodiments, the anti-CLEC2D antibodies or a composition comprising the anti-CLEC2D antibodies of the disclosure, are used in a method of treating a disease or disorder including but not limited to polymyalgia rheumatica, primary biliary sclerosis, sclerosing cholangitis, autoimmune hepatitis, Type 1 Diabetes Mellitus, Hashimoto&#39;s thyroiditis, Graves&#39; disease, multiple sclerosis (MS), Guillain-Barre syndrome, Addison&#39;s disease, and/or Raynaud&#39;s phenomenon and Goodpasture&#39;s syndrome, in a subject in need thereof, wherein the method comprises administering the anti-CLEC2D antibodies or a composition comprising the anti-CLEC2D antibodies in an amount effective for treatment or alleviating the symptoms of the disease in the subject. 
     In some embodiments, the anti-CLEC2D antibodies or a composition comprising the anti-CLEC2D antibodies of the disclosure, are used in a method of treating a disease or disorder including but not limited to diseases linked with cancer and cancers, in a subject in need thereof, wherein the method comprises administering the anti-CLEC2D antibodies or a composition comprising the anti-CLEC2D antibodies in an amount effective for treatment or alleviating the symptoms of the disease in the subject. 
     In some embodiments, the anti-CLEC2D antibodies or a composition comprising the anti-CLEC2D antibodies of the disclosure, are used in a method of treating a disease or disorder including but not limited to diseases linked with cancer and cancers, which comprise breast cancer, prostate cancer, endometrial cancer, uterine cancer, bladder cancer, kidney cancer, esophageal cancer, squamous cell carcinoma, uveal melanoma, glioma, glioblastoma, myeloma, pheochromocytoma, paraganglioma, follicular lymphoma, renal cell carcinoma, cendcal cancer, ovarian cancer, cervical cancer, lung cancer, colorectal cancer, brain cancer, pancreatic cancer, gastric cancer, intestinal cancer, testicular cancer, skin cancer, thyroid cancer, thymoma, head and neck cancer, liver cancer, pharynx cancer, adrenocortical cancer, cholangiocarcinoma, mesothelioma, sarcoma, leukemia, lymphoma, Hodgkin&#39;s disease, multiple myeloma, melanoma, astrocytoma, stomach cancer, pulmonary adenocarcinoma, adenocarcinoma, acinic cell adenocarcinoma, adrenal cortical carcinomas, alveoli cell carcinoma, anaplastic carcinoma, basaloid carcinoma, basal cell carcinoma, bronchiolar carcinoma, bronchogenic carcinoma, renaladinol carcinoma, embryonal carcinoma, anometroid carcinoma, fibrolamolar liver cell carcinoma, follicular carcinomas, giant cell carcinomas, hepatocellular carcinoma, intraepidermal carcinoma, intraepithelial carcinoma, leptomanigio carcinoma, medullary carcinoma, melanotic carcinoma, menigual carcinoma, mesometonephric carcinoma, oat cell carcinoma, squamal cell carcinoma, sweat gland carcinoma, transitional cell carcinoma, tubular cell carcinoma, ameloblastic sarcoma, angiolithic sarcoma, botryoid sarcoma, endometrial stroma sarcoma, ewing sarcoma, fascicular sarcoma, giant cell sarcoma, granulositic sarcoma, immunoblastic sarcoma, juxaccordial osteogenic sarcoma, coppices sarcoma, leukocytic sarcoma (leukemia), lymphatic sarcoma (lympho sarcoma), medullary sarcoma, myeloid sarcoma (granulocitic sarcoma), austiogenci sarcoma, periosteal sarcoma, reticulum cell sarcoma (histiocytic lymphoma), round cell sarcoma, spindle cell sarcoma, synovial sarcoma, telangiectatic audiogenic sarcoma, Burkitt&#39;s lymphoma, NPDL, NML, NH, diffuse lymphomas, Hodgkin&#39;s lymphoma, non-Hodgkin&#39;s lymphoma, B-cell lymphoma, T-cell lymphoma, diffuse large B-cell lymphoma, acute myeloid lymphoma, chronic lymphocytic leukemia, chronic myeoloid leukemia, mantle cell lymphoma, and follicular lymphoma, in a subject in need thereof, wherein the method comprises administering the anti-CLEC2D antibodies or a composition comprising the anti-CLEC2D antibodies in an amount effective for treatment or alleviating the symptoms of the disease in the subject. 
     In some embodiments, the anti-CLEC2D antibodies or a composition comprising the anti-CLEC2D antibodies of the disclosure, are used in a method of treating a disease or disorder including but not limited to diseases linked with a metastatic cancer or cancers, in a subject in need thereof, wherein the method comprises administering the anti-CLEC2D antibodies or a composition comprising the anti-CLEC2D antibodies in an amount effective for treatment or alleviating the symptoms of the disease in the subject. 
     In some embodiments, the anti-CLEC2D antibodies or a composition comprising the anti-CLEC2D antibodies of the disclosure, are used in a method of treating a disease or disorder including but not limited to diseases linked with a metastatic cancer or cancers, in a subject in need thereof, wherein the method comprises administering the anti-CLEC2D antibodies or a composition comprising the anti-CLEC2D antibodies in an amount effective for treatment or alleviating the symptoms of the disease in the subject. 
     In some embodiments, the anti-CLEC2D antibodies or a composition comprising the anti-CLEC2D antibodies of the disclosure, are used in a method of treating a disease or disorder including but not limited to diseases linked with a metastatic cancer or cancers to bone, in a subject in need thereof, wherein the method comprises administering the anti-CLEC2D antibodies or a composition comprising the anti-CLEC2D antibodies in an amount effective for treatment or alleviating the symptoms of the disease in the subject. 
     In some embodiments, the anti-CLEC2D antibodies or a composition comprising the anti-CLEC2D antibodies of the disclosure, are used in a method of treating a disease or disorder including but not limited to diseases linked with a metastatic cancer or cancers, wherein the metastatic cancer is breast, lung, renal, multiple myeloma, thyroid, prostate, adenocarcinoma, blood cell malignancies, including leukemia and lymphoma; head and neck cancers; gastrointestinal cancers, including esophageal cancer, stomach cancer, colon cancer, intestinal cancer, colorectal cancer, rectal cancer, pancreatic cancer, liver cancer, cancer of the bile duct or gall bladder; malignancies of the female genital tract, including ovarian carcinoma, uterine endometrial cancers, vaginal cancer, and cervical cancer; bladder cancer; brain cancer, including neuroblastoma; sarcoma, osteosarcoma; and skin cancer, including malignant melanoma or squamous cell cancerin a subject in need thereof, wherein the method comprises administering the anti-CLEC2D antibodies or a composition comprising the anti-CLEC2D antibodies in an amount effective for treatment or alleviating the symptoms of the disease in the subject. 
     In some embodiments, the anti-CLEC2D antibody and compositions of the disclosure, are used in a method of treatment of a subject by organ transplant or adoptive immune cell transplant. In some embodiments, the anti-CLEC2D antibody and compositions of the disclosure, block CD161 and CLEC2D interaction and reduces Graft vs Host rejection, due to killing if recipient dendritic cells by alloreactive NK cells. 
     In some embodiments, the anti-CLEC2D antibody and compositions of the disclosure, are used in a method of treatment of an infectious disease in a subject caused by microorganisms including but not limited to bacteria, fungi, protozoa, parasites, and viruses. In some embodiments, the anti-CLEC2D antibody and compositions of the disclosure, is used in a method of treatment of a bacterial disease in a subject caused by any one or more of (or any combination of)  Acinetobacter baumanii, Actinobacillus  sp., Actinomycetes,  Actinomyces  sp. (such as  Actinomyces israelii  and  Actinomyces naeslundii ),  Aeromonas  sp. (such as  Aeromonas hydrophila, Aeromonas veronii biovar sobria  ( Aeromonas sobria ), and  Aeromonas caviae ),  Anaplasma phagocytophilum, Anaplasma  marginale  Alcaligenes xylosoxidans, Acinetobacter baumanii, Actinobacillus actinomycetemcomitans, Bacillus  sp. (such as  Bacillus anthracis, Bacillus cereus, Bacillus subtilis, Bacillus thuringiensis , and  Bacillus stearothermophilus ),  Bacteroides  sp. (such as  Bacteroides fragilis ),  Bartonella  sp. (such as  Bartonella bacilliformis  and  Bartonella henselae, Bifidobacterium  sp.,  Bordetella  sp. (such as  Bordetella pertussis, Bordetella parapertussis , and  Bordetella bronchiseptica ),  Borrelia  sp. (such as  Borrelia recurrentis ,and  Borrelia burgdorferi ),  Brucella  sp. (such as  Brucella abortus, Brucella canis, Brucella melintensis  and  Brucella suis ),  Burkholderia  sp. (such as  Burkholderia pseudomallei  and  Burkholderia cepacia ),  Campylobacter  sp. (such as  Campylobacter jejuni, Campylobacter coli, Campylobacter lari  and  Campylobacter fetus ),  Capnocytophaga  sp.,  Cardiobacterium hominis, Chlamydia trachomatis, Chlamydophila pneumoniae, Chlamydophila psittaci, Citrobacter  sp.  Coxiella burnetii, Corynebacterium  sp. (such as,  Corynebacterium diphtheriae, Corynebacterium jeikeum  and  Corynebacterium ),  Clostridium  sp. (such as  Clostridium perfringens, Clostridium difficile, Clostridium botulinum  and  Clostridium tetani ), Eikenella corrodens,  Enterobacter  sp. (such as  Enterobacter aerogenes, Enterobacter agglomerans, Enterobacter cloacae  and  Escherichia coli , including opportunistic  Escherichia coli , such as enterotoxigenic  E. coli , enteroinvasive  E. coli , enteropathogenic  E. coli , enterohemorrhagic  E. coli , enteroaggregative  E. coli  and uropathogenic  E. coli )  Enterococcus  sp. (such as  Enterococcus faecalis  and  Enterococcus faecium ),  Ehrlichia  sp. (such as  Ehrlichia  chafeensia and  Ehrlichia canis ),  Epidermophyton floccosum, Erysipelothrix rhusiopathiae, Eubacterium  sp.,  Francisella tularensis, Fusobacterium nucleatum, Gardnerella vaginalis, Gemella morbillorum, Haemophilus  sp. (such as  Haemophilus influenzae, Haemophilus ducreyi, Haemophilus aegyptius, Haemophilus parainfluenzae, Haemophilus haemolyticus  and  Haemophilus parahaemolyticus, Helicobacter  sp. (such as  Helicobacter pylori, Helicobacter cinaedi  and  Helicobacter fennelliae ),  Kingella kingii, Klebsiella  sp. (such as  Klebsiella pneumoniae, Klebsiella granulomatis  and  Klebsiella oxytoca ),  Lactobacillus  sp.,  Listeria monocytogenes, Leptospira interrogans, Legionella pneumophila, Leptospira interrogans, Peptostreptococcus  sp.,  Mannheimia hemolytica, Microsporum canis, Moraxella catarrhalis, Morganella  sp.,  Mobiluncus  sp.,  Micrococcus  sp.,  Mycobacterium  sp. (such as  Mycobacterium leprae, Mycobacterium tuberculosis, Mycobacterium paratuberculosis, Mycobacterium intracellulare, Mycobacterium avium, Mycobacterium bovis , and  Mycobacterium marinum ),  Mycoplasm  sp. (such as  Mycoplasma pneumoniae, Mycoplasma hominis , and  Mycoplasma genitalium ),  Nocardia  sp. (such as  Nocardia asteroides, Nocardia cyriacigeorgica  and  Nocardia brasiliensis ),  Neisseria  sp. (such as  Neisseria gonorrhoeae  and  Neisseria meningitidis ),  Pasteurella multocida, Pityrosporum orbiculare  ( Malassezia furfur ),  Plesiomonas shigelloides. Prevotella  sp.,  Porphyromonas  sp.,  Prevotella melaninogenica, Proteus  sp. (such as  Proteus vulgaris  and  Proteus mirabilis ),  Providencia  sp. (such as  Providencia alcalifaciens, Providencia rettgeri  and  Providencia stuartii ),  Pseudomonas aeruginosa, Propionib acterium acnes, Rhodococcus equi, Rickettsia  sp. (such as  Rickettsia rickettsii, Rickettsia akari  and  Rickettsia prowazekii, Orientia tsutsugamushi  (formerly:  Rickettsia tsutsugamushi ) and  Rickettsia typhi ),  Rhodococcus  sp.,  Serratia marcescens, Stenotrophomonas maltophilia, Salmonella  sp. (such as  Salmonella enterica, Salmonella typhi, Salmonella paratyphi, Salmonella enteritidis, Salmonella cholerasuis  and  Salmonella typhimurium ),  Serratia  sp. (such as  Serratia marcesans  and  Serratia liquifaciens ),  Shigella  sp. (such as  Shigella dysenteriae, Shigella flexneri, Shigella boydii  and  Shigella sonnei ),  Staphylococcus  sp. (such as  Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus hemolyticus, Staphylococcus saprophyticus ),  Streptococcus  sp. (such as  Streptococcus pneumoniae  (for example chloramphenicol-resistant serotype 4  Streptococcus pneumoniae , spectinomycin-resistant serotype 6B  Streptococcus pneumoniae , streptomycin-resistant serotype 9V  Streptococcus pneumoniae , erythromycin-resistant serotype 14  Streptococcus pneumoniae , optochin-resistant serotype 14  Streptococcus pneumoniae , rifampicin-resistant serotype 18C  Streptococcus pneumoniae , tetracycline-resistant serotype 19F  Streptococcus pneumoniae , penicillin-resistant serotype 19F  Streptococcus pneumoniae , and trimethoprim-resistant serotype 23F  Streptococcus pneumoniae , chloramphenicol-resistant serotype 4  Streptococcus pneumoniae , spectinomycin-resistant serotype 6B  Streptococcus pneumoniae , streptomycin-resistant serotype, 9V  Streptococcus pneumoniae , optochin-resistant serotype 14  Streptococcus pneumoniae , rifampicin-resistant serotype 18C  Streptococcus pneumoniae , penicillin-resistant serotype 19F,  Streptococcus pneumoniae , or trimethoprim-resistant serotype 23F  Streptococcus pneumoniae ),  Streptococcus agalactiae, Streptococcus mutans, Streptococcus pyogenes , Group A streptococci,  Streptococcus pyogenes , Group B streptococci,  Streptococcus agalactiae , Group C streptococci,  Streptococcus anginosus, Streptococcus  equismilis, Group D streptococci,  Streptococcus bovis , Group F streptococci, and  Streptococcus anginosus  Group G streptococci),  Spirillum minus, Streptobacillus moniliformi, Treponema  sp. (such as  Treponema carateum, Treponema petenue, Treponema pallidum  and  Treponema endemicum, Trichophyton rubrum, T. mentagrophytes, Tropheryma whippelii, Ureaplasma urealyticum, Veillonella  sp.,  Vibrio  sp. (such as  Vibrio cholerae, Vibrio parahemolyticus, Vibrio vulnificus, Vibrio parahaemolyticus, Vibrio vulnificus,Vibrio alginolyticus, Vibrio mimicus, Vibrio hollisae, Vibrio fluvialis, Vibrio metchnikovii, Vibrio damsela  and  Vibrio furnisii ),  Yersinia  sp. (such as  Yersinia enterocolitica, Yersinia pestis , and  Yersinia pseudotuberculosis ) and  Xanthomonas maltophilia  among others. 
     In some embodiments, the anti-CLEC2D antibody and compositions of the disclosure, is used in a method of treatment of a fungal disease in a subject caused by any one or more of (or any combination of)  Aspergillus, Blastomyces, Candidiasis, Coccidiodomycosis, Cryptococcus neoformans, Cryptococcus gatti , sp.  Histoplasma  sp. (such as  Histoplasma capsulatum ),  Pneumocystis  sp. (such as  Pneumocystis jirovecii ),  Stachybotrys  (such as  Stachybotrys chartarum ),  Mucroymcosis, Sporothrix , fungal eye infections ringworm,  Exserohilum, Cladosporium.    
     In some embodiments, the anti-CLEC2D antibody and compositions of the disclosure, is used in a method of treatment of a protozoan disease in a subject caused by any one or more of (or any combination of) Euglenozoa, Heterolobosea, Diplomonadida, Amoebozoa, Blastocystic, and Apicomplexa. Example Euglenoza include, but are not limited to,  Trypanosoma cruzi  (Chagas disease),  T. brucei  gambiense,  T. brucei  rhodesiense,  Leishmania braziliensis, L. infantum, L. mexicana, L. major, L. tropica , and  L. donovani . Example Heterolobosea include, but are not limited to,  Naegleria fowleri . Example Diplomonadids include, but are not limited to,  Giardia intestinalis  ( G. lamblia, G. duodenalis ). Example Amoebozoa include, but are not limited to,  Acanthamoeba castellanii, Balamuthia madrillaris, Entamoeba histolytica . Example Blastocysts include, but are not limited to,  Blastocystic hominis . Example Apicomplexa include, but are not limited to,  Babesia microti, Cryptosporidium parvum, Cyclospora cayetanensis, Plasmodium falciparum, P. vivax, P. ovale, P. malariae , and  Toxoplasma gondii.    
     In some embodiments, the anti-CLEC2D antibody and compositions of the disclosure, is used in a method of treatment of a viral disease in a subject caused by any one or more of (or any combination of) Ebolavirus, measles virus, SARS, Chikungunya virus, hepatitis viruses, Marburg virus, yellow fever virus, MERS, Dengue virus, Lassa fever virus, influenza virus, rhabdovirus or HIV. A hepatitis virus may include hepatitis A, hepatitis B, or hepatitis C. 
     In some embodiments, the anti-CLEC2D antibody and compositions of the disclosure, is used in a method of treatment of a viral disease in a subject caused by any one or more of (or any combination of) a human respiratory syncytial virus, Sudan ebola virus, Bundibugyo virus, Tai Forest ebola virus, Reston ebola virus, Achimota, Aedes flavivirus, Aguacate virus, Akabane virus, Alethinophid reptarenavirus, Allpahuayo mammarenavirus, Amapari mmarenavirus, Andes virus, Apoi virus, Aravan virus, Aroa virus, Arumwot virus, Atlantic salmon paramyxovirus, Australian bat lyssavirus, Avian bornavirus, Avian metapneumovirus, Avian paramyxoviruses, penguin or Falkland Islandsvirus, BK polyomavirus, Bagaza virus, Banna virus, Bat herpesvirus, Bat sapovirus, Bear Canon mammarenavirus, Beilong virus, Betacoronavirus, Betapapillomavirus 1-6, Bhanja virus, Bokeloh bat lyssavirus, Borna disease virus, Bourbon virus, Bovine hepacivirus, Bovine parainfluenza virus 3, Bovine respiratory syncytial virus, Brazoran virus, Bunyamwera virus, Caliciviridae virus. California encephalitis virus, Candiru virus, Canine distemper virus, Canine pneumovirus, Cedar virus, Cell fusing agent virus, Cetacean morbillivirus, Chandipura virus, Chaoyang virus, Chapare mammarenavirus, Chikungunya virus, Colobus monkey papillomavirus, Colorado tick fever virus, Cowpox virus, Crimean-Congo hemorrhagic fever virus, Culex flavivirus, Cupixi mammarenavirus, Dengue virus, Dobrava-Belgrade virus, Donggang virus, Dugbe virus, Duvenhage virus, Eastern equine encephalitis virus, Entebbe bat virus, Enterovirus A-D, European bat lyssavirus 1-2, Eyach virus, Feline morbillivirus, Fer-de-Lance paramyxovirus, Fitzroy River virus, Flaviviridae virus, Flexal mammarenavirus, GB virus C, Gairo virus, Gemycircularvirus, Goose paramyxovirus SF02, Greatlsland virus, Guanarito mammarenavirus, Hantaan virus, Hantavirus Z10, Heartland virus, Hendra virus, Hepatitis A/B/C/E, Hepatitis delta virus, Human bocavirus, Human coronavirus, Human endogenous retrovirus K, Human enteric coronavirus, Human genital-associated circular DNA virus-1, Human herpesvirus 1-8, Human immunodeficiency virus 1/2, Human mastadenovirus AG, Human papillomavirus, Human parainfluenza virus 1-4, Human paraechovirus, Human picornavirus, Human smacovirus, Ikoma lyssavirus, Ilheus virus, Influenza A-C, Ippy mammarenavirus, Irkut virus, J-virus, JC polyomavirus, Japanese encephalitis virus, Junin mammarenavirus, KI polyomavirus, Kadipiro virus, Kamiti River virus, Kedougou virus, Khuj and virus, Kokobera virus, Kyasanur forest disease virus, Lagos bat virus, Langat virus, Lassa mammarenavirus, Latino mammarenavirus, Leopards Hill virus, Liao ning virus, Ljungan virus, Lloviu virus, Louping ill virus, Lujo mammarenavirus, Luna mammarenavirus, Lunk virus, Lymphocytic choriomeningitis mammarenavirus, Lyssavirus Ozernoe, MSSI2Y225 virus, Machupo mammarenavirus, Mamastrovirus 1, Manzanilla virus, Mapuera virus, Marburg virus, Mayaro virus, Measles virus, Menangle virus, Mercadeo virus, Merkel cell polyomavirus, Middle East respiratory syndrome coronavirus, Mobala mammarenavirus, Modoc virus, Moijang virus, Mokolo virus, Monkeypox virus, Montana myotis leukoenchalitis virus, Mopeia lassa virus reassortant 29, Mopeia mammarenavirus, Morogoro virus, Mossman virus, Mumps virus, Murine pneumonia virus, Murray Valley encephalitis virus, Nariva virus, Newcastle disease virus, Nipah virus, Norwalk virus, Norway rat hepacivirus, Ntaya virus, O&#39;nyong-nyong virus, Oliveros mammarenavirus, Omsk hemorrhagic fever virus, Oropouche virus, Parainfluenza virus 5, Parana mammarenavirus, Parramatta River virus, Peste-des-petits-ruminants virus, Pichande mammarenavirus, Picornaviridae virus, Pirital mammarenavirus, Piscihepevirus A, Porcine parainfluenza virus 1, porcine rubulavirus, Powassan virus, Primate T-lymphotropic virus 1-2, Primate erythroparvovirus 1, Punta Toro virus, Puumala virus, Quang Binh virus, Rabies virus, Razdan virus, Reptile bornavirus 1, Rhinovirus A-B, Rift Valley fever virus, Rinderpest virus, Rio Bravo virus, Rodent Torque Teno virus, Rodent hepacivirus, Ross River virus, Rotavirus A-I, Royal Farm virus, Rubella virus, Sabia mammarenavirus, Salem virus, Sandfly fever Naples virus, Sandfly fever Sicilian virus, Sapporo virus, Sathuperi virus, Seal anellovirus, Semliki Forest virus, Sendai virus, Seoul virus, Sepik virus, Severe acute respiratory syndrome-related coronavirus, Severe fever with thrombocytopenia syndrome virus, Shamonda virus, Shimoni bat virus, Shuni virus, Simbu virus, Simian torque teno virus, Simian virus 40-41, Sin Nombre virus, Sindbis virus,Small anellovirus, Sosuga virus, Spanish goat encephalitis virus, Spondweni virus, St. Louisencephalitis virus, Sunshine virus, TTV-like mini virus, Tacaribe mammarenavirus, Taila virus, Tamana bat virus, Tamiami mammarenavirus, Tembusu virus, Thogoto virus, Thottapalayam virus, Tick-borne encephalitis virus, Tioman virus, Togaviridae virus, Torque teno canis virus, Torque teno douroucouli virus, Torque teno felis virus, Torque teno midi virus, Torque teno sus virus, Torque teno tamarin virus, Torque teno virus, Torque teno zalophus virus, Tuhoko virus, Tula virus, Tupaia paramyxovirus, Usutu virus, Uukuniemi virus, Vaccinia virus, Variola virus, Venezuelan equine encephalitis virus, Vesicular stomatitis Indiana virus, WU Polyomavirus, Wesselsbron virus, West Caucasian bat virus, West Nile virus, Western equine encephalitis virus, Whitewater Arroyo mammarenavirus, Yellow fever virus, Yokose virus, Yug Bogdanovac virus, Zaire ebolavirus, Zika virus, or  Zygosaccharomyces bailii  virus Z viral sequence. Examples of diseases caused by RNA viruses that may be treated include one or more of (or any combination of) Coronaviridae virus, a Picornaviridae virus, a Caliciviridae virus, a Flaviviridae virus, a Togaviridae virus, a Bornaviridae, a Filoviridae, a Paramyxoviridae, a Pneumoviridae, a Rhabdoviridae, an Arenaviridae, a Bunyaviridae, an Orthomyxoviridae, or a Deltavirus. In certain embodiments, the virus is Coronavirus, SARS, Poliovirus, Rhinovirus, Hepatitis A, Norwalk virus, Yellow fever virus, West Nile virus, Hepatitis C virus, Dengue fever virus, Zika virus, Rubella virus, Ross River virus, Sindbis virus, Chikungunya virus, Borna disease virus, Ebola virus, Marburg virus, Measles virus, Mumps virus, Nipah virus, Hendra virus, Newcastle disease virus, Human respiratory syncytial virus, Rabies virus, Lassa virus, Hantavirus, Crimean-Congo hemorrhagic fever virus, Influenza, or Hepatitis D virus. In certain embodiments, the virus is retrovirus, including but not limited to one or more of or any combination of viruses of the Genus Alpharetrovirus, Betaretrovirus, Gammaretrovirus, Deltaretrovirus, Epsilonretrovirus, Lentivirus, Spumavirus, or the Family Metaviridae, Pseudoviridae, and Retroviridae (including HIV), Hepadnaviridae (including Hepatitis B virus), and Caulimoviridae (including Cauliflower mosaic virus). 
     In some embodiments, the infectious diseases comprises a chronic viral infection, such as HIV. In some embodiments, the infectious disease comprises a chronic bacterial infection such as tuberculosis (TB). In some embodiments, the infectious disease comprises a chronic parasitic infection such as malaria. 
     In some embodiments, the anti-CLEC2D antibodies or a composition comprising the anti-CLEC2D antibodies of the disclosure, are used in a method of treating a disease or disorder characterized by increased expression of CLEC2D on the surface of various cells of a subject in need thereof, comprising administering to a subject in need thereof one or more anti-CLEC2D antibodies of the disclosure as therapeutic agents in an amount sufficient to either: (i) block binding of the CLEC2D on the various cells to CD161 on the surface of an immune cell; (ii) reduce expression of CLEC2D on the various cells; (iii) reduce expression of one or more genes induced in an immune cell by binding of the CLEC2D to the CD161 on the immune cell (iv) binding to and/or activating one or more Fc receptors on the surface of the immune cell, (v) bind to CLEC2D on the surface of an immune cells and activate the immune cell, or any combination thereof. 
     In some embodiments, the invention relates to a method of assessing the efficacy of a therapeutic agent in a subject suffering from a cancer or tumor or both, comprising: a) detecting the number of viable and/or proliferating cancer cells in a sample from a subject; b) administering a therapeutically effective amount of one or more anti-CLEC2D antibodies of the disclosure to the subject; c) repeating step a) one or more times; and d) comparing the number of viable and/or proliferating cancer cells detected in steps a) to those detected in step c), wherein the anti-CLEC2D antibodies: (i) bind to CLEC2D on the surface of the cancer cells and inhibits the interaction between the CLEC2D on the tumor cells and CD161 on the surface of immune cells; (ii) bind to CLEC2D on the surface of the cancer cells and Fc receptors on the surface of immune cells to induce lysis of the cancer cell; (iii) bind to CLEC2D on the surface of immune cells and activate the immune cells; or a combination thereof, wherein the absence of, or decrease in number of viable and/or proliferating cancer cells detected in step c) as compared to the number of viable and/or proliferating cancer cells detected in step a) indicates that the agent is effective. 
     In some embodiments, the anti-CLEC2D antibodies or a composition comprising the anti-CLEC2D and bodies of the disclosure, may enhance the function of mucosal associated invariant T (MAIT) cells, NK cells or T cells. 
     In some embodiments, the invention relates to a method of treatment of a disease or disorder in a subject, wherein the method comprises administering to the subject in need thereof, a combination of a therapeutically effective amount of an anti-CLEC2D antibody of the disclosure and a therapeutically effective amount of at least a second therapeutic agent. In some embodiments, the at least one second therapeutic agent as disclosed herein, comprises a therapeutic antibody against a protein or antigen expressed on the surface of a tumor cell or immune cell. 
     In some embodiments, the at least one second therapeutic agent as disclosed herein, comprises a therapeutic antibody against a protein or antigen expressed on the surface of a tumor cell, that induces apoptosis of the tumor cell. In some embodiments, the at least one second therapeutic agent as disclosed herein, comprises a therapeutic antibody against a protein or antigen expressed on the surface of a tumor cell, that induces killing by the immune cell through antibody directed cellular cytotoxicity (ADCC) or complement directed cytotoxicity (CDC). In some embodiments, the at least one second therapeutic agent as disclosed herein, comprises a therapeutic antibody against a protein or antigen expressed on the surface of an immune cell, that induces activation of the immune cell. In some embodiments, the at least one second therapeutic agent as disclosed herein, comprises a therapeutic antibody against a protein or antigen expressed on the surface of an immune cell, that induces cytokine production by the immune cell. In some embodiments, the at least one second therapeutic agent as disclosed herein, comprises a therapeutic antibody against a protein or antigen expressed on the surface of an immune cell, that induces chemokine production by the immune cell. In some embodiments, the at least one second therapeutic agent as disclosed herein, comprises a therapeutic antibody against a protein or antigen expressed on the surface of an immune cell, that induces production of inflammatory cytokines of the immune cell. In some embodiments, the at least one second therapeutic agent as disclosed herein, comprises a therapeutic antibody against a protein or antigen expressed on the surface of an immune cell, that activates the immune cells to recognize and induce cytotoxicity in a cancer cell. In some embodiments, the at least one second therapeutic agent as disclosed herein, comprises a therapeutic antibody against a protein or antigen expressed on the surface of an immune cell, that activates the immune cells to recognize and induce cytotoxicity in cell infected with a pathogen, wherein the pathogen includes but is not limited to a virus or a bacteria. 
     In some embodiments, the methods of treatment of a disease or disorder in a subject, as disclosed herein, comprises administering the anti-CLEC2D antibodies or a composition comprising the anti-CLEC2D antibodies of the disclosure and at least a second therapeutic agent, sequentially or simultaneously. 
     Treatment of Inflammatory Diseases 
     In some embodiments, the disease or disorder treated by the antibodies and pharmaceutical compositions comprising the same of the disclosure comprises an inflammatory or autoimmune disease or disorder. 
     As used herein, the term “inflammatory disorders” refers to pathological states resulting in inflammation, typically caused by neutrophil chemotaxis. 
     As used herein, autoimmune diseases or disorders are caused when the body&#39;s immune system, which normally defends the body against bacteria, viruses and other infective agents, attacks ‘self’ tissue, cells and organs. The mobilization of the immune system against such “self” targets is termed autoimmunity. Although some autoimmunity is present in every individual, rigid control systems suppress the self-recognizing cells of the immune system to an extent that the autoimmunity is normally asymptomatic. Disease states arise when there is some interruption in the control system, allowing the autoimmune cells to escape suppression, or when there is some change in a target tissue such that it is no longer recognized as self Autoimmune disorders can be characterized by inflammatory responses. 
     Exemplary, but non-limiting examples of inflammatory or autoimmune disorders include, but are not limited to seronegative spondyloarthropathies, connective tissue diseases, inflammatory bowel diseases, arthritis, inflammatory skin conditions, inflammatory lung diseases, inflammatory renal disease, systemic vasculitis, macrophage activation diseases, polymyalgia rheumatica, primary biliary sclerosis, sclerosing cholangitis, autoimmune hepatitis, Type 1 Diabetes Mellitus, Hashimoto&#39;s thyroiditis, Graves&#39; disease, multiple sclerosis (MS), Guillain-Barre syndrome, Addison&#39;s disease, Raynaud&#39;s phenomenon and Goodpasture&#39;s syndrome. 
     In some embodiments, a therapeutically effective amount of an antibody of pharmaceutical composition comprising same of the disclosure alleviates or prevents a sign or a symptom of an inflammatory or autoimmune disorder. 
     In some embodiments, a therapeutically effective amount of an antibody of pharmaceutical composition comprising same of the disclosure reduces an amount of inflammation in one or more tissues or organs of the subject. 
     In some embodiments, a therapeutically effective amount of an antibody of pharmaceutical composition comprising same of the disclosure transiently reduces or inhibits one or more aspects of the disease or of the immune response. Such a transient inhibition or reduction of one or more aspects of the disease or of the immune system can last for hours, days, weeks, or months. Preferably, the transient inhibition or reduction in one or more aspects of the disease or of the immune response last for a few hours (e.g., 2 hours, 4 hours, 6 hours, 8 hours, 12 hours, 14 hours, 16 hours, 18 hours, 24 hours, 36 hours, or 48 hours), a few days (e.g., 3 days, 4 days, 5 days, 6 days, 7 days, or 14 days), or a few weeks (e.g., 3 weeks, 4 weeks, 5 weeks or 6 weeks). 
     The prophylactic, therapeutic or immunomodulatory activity of an antibody or pharmaceutical composition comprising an antibody of the disclosure can be determined in vitro and/or in vivo by any technique well-known to one skilled in the art, including, e.g., by CTL assays, proliferation assays, and immunoassays (e.g., ELISAs) for the expression of particular proteins such as co-stimulatory molecules and cytokines. 
     Treatment of Cancer 
     As used herein, the term “severity” is meant to describe the potential of cancer to transform from a precancerous, or benign, state into a malignant state. Alternatively, or in addition, severity is meant to describe a cancer stage, for example, according to the TNM system (accepted by the International Union Against Cancer (UICC) and the American Joint Committee on Cancer (AJCC)) or by other art-recognized methods. Cancer stage refers to the extent or severity of the cancer, based on factors such as the location of the primary tumor, tumor size, number of tumors, and lymph node involvement (spread of cancer into lymph nodes). Alternatively, or in addition, severity is meant to describe the tumor grade by art-recognized methods (see, National Cancer Institute, www.cancer.gov). Tumor grade is a system used to classify cancer cells in terms of how abnormal they look under a microscope and how quickly the tumor is likely to grow and spread. Many factors are considered when determining tumor grade, including the structure and growth pattern of the cells. The specific factors used to determine tumor grade vary with each type of cancer. Severity also describes a histologic grade, also called differentiation, which refers to how much the tumor cells resemble normal cells of the same tissue type (see, National Cancer institute, www.cancer.gov). Furthermore, severity describes a nuclear grade, which refers to the size and shape of the nucleus in tumor cells and the percentage of tumor cells that are dividing (see, National Cancer institute, www.cancer.gov). 
     In another aspect of this disclosure, severity describes the degree to which a tumor has secreted growth factors, degraded the extracellular matrix, become vascularized, lost adhesion to juxtaposed tissues, or metastasized. Moreover, severity describes the number of locations to which a primary tumor has metastasized. Finally, severity includes the difficulty of treating tumors of varying types and locations. For example, inoperable tumors, those cancers Which have greater access to multiple body systems (hematological and immunological tumors), and those which are the most resistant to traditional treatments are considered most severe. In these situations, prolonging the life expectancy of the subject and/or reducing pain, decreasing the proportion of cancerous cells or restricting cells to one system, and improving cancer stage/tumor grade/histological grade/nuclear grade are considered alleviating a sign or symptom of the cancer. 
     Cancer is a group of diseases that may cause almost any sign or symptom. The signs and symptoms will depend on where the cancer is, the size of the cancer, and how much it affects the nearby organs or structures. If a cancer spreads (metastasizes), then symptoms may appear in different parts of the body. 
     Treating cancer can result in a reduction in size of a tumor. A reduction in size of a tumor may also be referred to as “tumor regression”. Preferably, after treatment, tumor size is reduced by 5% or greater relative to its size prior to treatment; more preferably, tumor size is reduced by 10% or greater; more preferably, reduced by 20% or greater; more preferably, reduced by 30% or greater; more preferably, reduced by 40% or greater; even more preferably, reduced by 50% or greater; and most preferably, reduced by greater than 75% or greater. Size of a tumor may be measured by any reproducible means of measurement. The size of a tumor may be measured as a diameter of the tumor. 
     Treating cancer can result in a reduction in tumor volume. Preferably, after treatment, tumor volume is reduced by 5% or greater relative to its size prior to treatment; more preferably, tumor volume is reduced by 10% or greater; more preferably, reduced by 20% or greater; more preferably, reduced by 30% or greater; more preferably, reduced by 40% or greater; even more preferably, reduced by 50% or greater; and most preferably, reduced by greater than 75% or greater. Tumor volume may be measured by any reproducible means of measurement. 
     Treating cancer results in a decrease in number of tumors. Preferably, after treatment, tumor number is reduced by 5% or greater relative to number prior to treatment; more preferably, tumor number is reduced by 10% or greater; more preferably, reduced by 20% or greater; more preferably, reduced by 30% or greater; more preferably, reduced by 40% or greater; even more preferably, reduced by 50% or greater; and most preferably, reduced by greater than 75%. Number of tumors may be measured by any reproducible means of measurement. The number of tumors may be measured by counting tumors visible to the naked eye or at a specified magnification. Preferably, the specified magnification is 2×, 3×, 4×, 5×, 10×, or 50×. 
     Treating cancer can result in a decrease in number of metastatic lesions in other tissues or organs distant from the primary tumor site. Preferably, after treatment, the number of metastatic lesions is reduced by 5% or greater relative to number prior to treatment; more preferably, the number of metastatic lesions is reduced by 10% or greater; more preferably, reduced by 20% or greater; more preferably, reduced by 30% or greater; more preferably, reduced by 40% or greater; even more preferably, reduced by 50% or greater; and most preferably, reduced by greater than 75%. The number of metastatic lesions may be measured by any reproducible means of measurement. The number of metastatic lesions may be measured by counting metastatic lesions visible to the naked eye or at a specified magnification. Preferably, the specified magnification is 2×, 3×, 4×, 5×, 10×, or 50×. 
     Treating cancer can result in an increase in average survival time of a population of treated subjects in comparison to a population receiving earlier alone. Preferably, the average survival time is increased by more than 30 days; more preferably, by more than 60 days; more preferably, by more than 90 days; and most preferably, by more than 120 days. An increase in average survival time of a population may be measured by any reproducible means. An increase in average survival time of a population may be measured, for example, by calculating for a population the average length of survival following initiation of treatment with an antibody or pharmaceutical composition comprising same. An increase in average survival time of a population may also be measured, for example, by calculating for a population the average length of survival following completion of a first round of treatment with an antibody or pharmaceutical composition comprising same. 
     Treating cancer can result in an increase in average survival time of a population of treated subjects in comparison to a population of untreated subjects. Preferably, the average survival time is increased by more than 30 days; more preferably, by more than 60 days; more preferably, by more than 90 days; and most preferably, by more than 120 days. An increase in average survival time of a population may be measured by any reproducible means. An increase in average survival time of a population may be measured, for example, by calculating for a population the average length of survival following initiation of treatment with an antibody or pharmaceutical composition comprising same. An increase in average survival time of a population may also be measured, for example, by calculating for a population the average length of survival following completion of a first round of treatment with an antibody or pharmaceutical composition comprising same of the present disclosure. 
     Treating cancer can result in increase in average survival time of a population of treated subjects in comparison to a population receiving monotherapy with a drug that is not an antibody of the present disclosure. Preferably, the average survival time is increased by more than 30 days; more preferably, by more than 60 days; more preferably, by more than 90 days; and most preferably, by more than 120 days. An increase in average survival time of a population may be measured by any reproducible means. An increase in average survival time of a population may be measured, for example, by calculating for a population the average length of survival following initiation of treatment with an antibody or pharmaceutical composition comprising same of the present disclosure. An increase in average survival time of a population may also be measured, for example, by calculating for a population the average length of survival following completion of a first round of treatment with an antibody or pharmaceutical composition comprising same of the present disclosure. 
     Treating cancer can result in a decrease in the mortality rate of a population of treated subjects in comparison to a population receiving carrier alone. Treating cancer can result in a decrease in the mortality rate of a population of treated subjects in comparison to an untreated population. Treating cancer can result in a decrease in the mortality rate of a population of treated subjects in comparison to a population receiving monotherapy with a drug that is not an antibody or a pharmaceutical composition comprising same of the present disclosure. Preferably, the mortality rate is decreased by more than 2%; more preferably, by more than 5%; more preferably, by more than 10%; and most preferably, by more than 25%. A decrease in the mortality rate of a population of treated subjects may be measured by any reproducible means. A decrease in the mortality rate of a population may be measured, for example, by calculating for a population the average number of disease-related deaths per unit time following initiation of treatment with an antibody. A decrease in the mortality rate of a population may also be measured, for example, by calculating for a population the average number of disease-related deaths per unit time following completion of a first round of treatment with an antibody. 
     Treating cancer can result in a decrease in tumor growth rate. Preferably, after treatment, tumor growth rate is reduced by at least 5% relative to number prior to treatment; more preferably, tumor growth rate is reduced by at least 10%; more preferably, reduced by at least 20%; more preferably, reduced by at least 30%; more preferably, reduced by at least 40%; more preferably, reduced by at least 50%; even more preferably, reduced by at least 50%; and most preferably, reduced by at least 75%. Tumor growth rate may be measured by any reproducible means of measurement. Tumor growth rate can be measured according to a change in tumor diameter per unit time. 
     Treating cancer can result in a decrease in tumor regrowth. Preferably, after treatment, tumor regrowth is less than 5%; more preferably, tumor regrowth is less than 10%; more preferably, less than 20%; more preferably, less than 30%; more preferably, less than 40%; more preferably, less than 50%; even more preferably, less than 30%; and most preferably, less than 75%. Tumor regrowth may be measured by any reproducible means of measurement. Tumor regrowth is measured, for example, by measuring an increase in the diameter of a tumor after a prior tumor shrinkage that followed treatment. A decrease in tumor regrowth is indicated by failure of tumors to reoccur after treatment has stopped. 
     Treating cancer can result in a reduction in the rate of cellular proliferation. Preferably, after treatment, the rate of cellular proliferation is reduced by at least 5%; inure preferably, by at least 10%; more preferably, by at least 20%; more preferably, by at least 30%; more preferably, by at least 40%; more preferably, by at least 50%; even more preferably, by at least 50%; and most preferably, by at least 75%. The rate of cellular proliferation may be measured by any reproducible means of measurement. The rate of cellular proliferation is measured, for example, by measuring the number of dividing cells in a tissue sample per unit time. 
     Treating cancer can result in a reduction in the proportion of proliferating cells. Preferably, after treatment, the proportion of proliferating cells is reduced by at least 5%; more preferably; by at least 10%; more preferably, by at least 20%; more preferably, by at least 30%; more preferably, by at least 40%; more preferably, by at least 50%, even more preferably, by at least 50%; and most preferably, by at least 75%. The proportion of proliferating cells may be measured by any reproducible means of measurement. Preferably, the proportion of proliferating cells is measured, for example, by quantifying the number of dividing cells relative to the number of nondividing cells in a tissue sample. The proportion of proliferating cells can be equivalent to the mitotic index. 
     Treating cancer can result in a decrease in size of an area or zone of cellular proliferation. Preferably, after treatment, size of an area or zone of cellular proliferation is reduced by at least 5% relative to its size prior to treatment; more preferably, reduced by at least 10%; more preferably, reduced by at least 20%; more preferably, reduced by at least 30%; more preferably, reduced by at least 40%; more preferably, reduced by at least 50%; even more preferably, reduced by at least 50%; and most preferably, reduced by at least 75%. Size of an area or zone of cellular proliferation may be measured by any reproducible means of measurement. The size of an area or zone of cellular proliferation may be measured as a diameter or width of an area or zone of cellular proliferation. Treating cancer can result in a decrease in the number or proportion of cells having an abnormal appearance or morphology. Preferably, after treatment, the number of cells having an abnormal morphology is reduced by at least 5% relative to its size prior to treatment; more preferably, reduced by at least 10%; more preferably, reduced by at least 20%; more preferably, reduced by at least 30%; more preferably, reduced by at least 40%; more preferably, reduced by at least 50%; even more preferably, reduced by at least 50%; and most preferably, reduced by at least 75%. An abnormal cellular appearance or morphology may be measured by any reproducible means of measurement. An abnormal cellular morphology can be measured by microscopy, e.g., using an inverted tissue culture microscope. An abnormal cellular morphology can take the form of nuclear pleiomorphism. 
     Treating cancer can result in cell death, and preferably, cell death results in a decrease of at least 10% in number of cells in a population. More preferably, cell death means a decrease of at least 20%; more preferably, a decrease of at least 30%; more preferably, a decrease of at least 40%; more preferably, a decrease of at least 50%; most preferably; a decrease of at least 75%. Number of cells in a population may be measured by any reproducible means. A number of cells in a population can be measured by fluorescence activated cell sorting (FACS), immunofluorescence microscopy and light microscopy. Methods of measuring cell death are as shown in Li et al., Proc Natl Acad Sci USA. 100(5): 2674-8, 2003. In an aspect; cell death occurs by apoptosis. 
     Monotherapies 
     In the some embodiments of the disclosure, the antibodies and compositions of the disclosure are administered as monotherapies for the treatment of a disease. 
     As used herein, “monotherapy” refers to the administration of a single active or therapeutic compound to a subject in need thereof. Preferably, monotherapy will involve administration of a therapeutically effective amount of an active compound. For example, cancer monotherapy with one of the antibodies of the present disclosure, or a pharmaceutical composition thereof, to a subject in need of treatment of cancer. Monotherapy may be contrasted with combination therapy, in which a combination of multiple active compounds is administered, preferably with each component of the combination present in a therapeutically effective amount. In one aspect, monotherapy with an antibody or pharmaceutical composition of the present disclosure is more effective than combination therapy in inducing a desired biological effect. 
     An antibody according to the disclosure can also be used as an agent for detecting the presence of CLEC2D (or a protein or a protein fragment thereof) in a sample. Preferably, the antibody contains a detectable label. Antibodies can be polyclonal, or more preferably, monoclonal. An intact antibody, or a fragment thereof (e.g., Fab, scFv, or F (ab)2 ) can be used. The term “labeled”, with regard to the probe or antibody, is intended to encompass direct labeling of the probe or antibody by coupling (i.e., physically linking) a detectable substance to the probe or antibody, as well as indirect labeling of the probe or antibody by reactivity with another reagent that is directly labeled. Examples of indirect labeling include detection of a primary antibody using a fluorescently-labeled secondary antibody and end-labeling of a DNA probe with biotin such that it can be detected with fluorescently-labeled streptavidin. The term “biological sample” is intended to include tissues, cells and biological fluids isolated from a subject, as well as tissues, cells and fluids present within a subject. Included within the usage of the term “biological sample”, therefore, is blood and a fraction or component of blood including blood serum, blood plasma, or lymph. That is, the detection method of the disclosure can be used to detect an analyte mRNA, protein, or genomic DNA in a biological sample in vitro as well as in vivo. For example, in vitro techniques for detection of an analyte mRNA includes Northern hybridizations and in situ hybridizations. In vitro techniques for detection of an analyte protein include enzyme linked immunosorbent assays (ELISAs), Western blots, immunoprecipitations, and immunofluorescence. In vitro techniques for detection of an analyte genomic DNA include Southern hybridizations. Procedures for conducting immunoassays are described, for example in “ELISA: Theory and Practice: Methods in Molecular Biology”, Vol. 42, J. R. Crowther (Ed.) Human Press, Totowa, N.J., 1995; “Immunoassay”, E. Diamandis and T. Christopoulus, Academic Press, Inc., San Diego, Calif., 1996; and “Practice and Theory of Enzyme Immunoassays”, P. Tijssen, Elsevier Science Publishers, Amsterdam, 1985. Furthermore, in vivo techniques for detection of an analyte protein include introducing into a subject a labeled anti-analyte protein antibody. For example, the antibody can be labeled with a radioactive marker whose presence and location in a subject can be detected by standard imaging techniques. 
     Antibodies directed against a CLEC2D protein (or a fragment thereof) may be used in methods known within the art relating to the localization and/or quantitation of a CLEC2D protein (e.g., for use in measuring levels of the CLEC2D protein within appropriate physiological samples, for use in diagnostic methods, for use in imaging the protein, and the like). In a given embodiment, antibodies specific to a CLEC2D protein, or derivative, fragment, analog or homolog thereof, that contain the antibody derived antigen binding domain, are utilized as pharmacologically active compounds (referred to hereinafter as “Therapeutics”). 
     An antibody specific for a CLEC2D protein of the disclosure can be used to isolate a CLEC2D polypeptide by standard techniques, such as immunoaffinity, chromatography or immunoprecipitation. Antibodies directed against a CLEC2D protein (or a fragment thereof) can be used diagnostically to monitor protein levels in tissue as part of a clinical testing procedure, e.g., to, for example, determine the efficacy of a given treatment regimen. Detection can be facilitated by coupling (i.e., physically linking) the antibody to a detectable substance. Examples of detectable substances include various enzymes, prosthetic groups, fluorescent materials, luminescent materials, bioluminescent materials, and radioactive materials. Examples of suitable enzymes include horseradish peroxidase, alkaline phosphatase, β-galactosidase, or acetylcholinesterase; examples of suitable prosthetic group complexes include streptavidin/biotin and avidin/biotin; examples of suitable fluorescent materials include umbelliferone, fluorescein, fluorescein isothiocyanate, rhodamine, dichlorotriazinylamine fluorescein, dansyl chloride or phycoerythrin; an example of a luminescent material includes luminol; examples of bioluminescent materials include luciferase, luciferin, and aequorin, and examples of suitable radioactive material include  125 I,  131 I,  35 S or  3 H. 
     Combination Therapies 
     In the some embodiments of the disclosure, the antibodies and compositions of the disclosure are administered as part of a combination therapy for the treatment of a disease. 
     For example, anti-CLEC2D antibodies have been tested in xenograft studies alone and in combination with a check point monoclonal antibody (anti PDL1). The combinatorial treatment with anti-CLEC2D and anti-PDL1 had revealed significant tumor growth reduction. Therefore, Anti-CLEC2D antibody can be used in combination with other therapies for therapeutic purposes. 
     These therapies include, but are not restricted to, T cell targeted immunomodulatory mechanisms, other immunomodulatory mechanisms, cancer vaccines, adoptive cell therapies, oncolytic viruses, additional antibody therapies including bispecific and other combinations of antibody fragments, radiotherapy, antibody drug conjugates, small interfering RNAs, chemotherapy, immunotherapy, immune checkpoint inhibitors, mitotic inhibitors or a combination thereof. 
     Chemotherapies, small molecules and biologics that can be administered in combination with an anti-CLEC2D antibodies or compositions of the disclosure include, but are not restricted to hormonal therapies, PARP inhibitors, Androgen receptor inhibitors, tyrosine kinase inhibitors, Abiraterone acetate, Enzalutamide, Apalutamide, Darolutamide, Phosphoinositide 3 Kinase Beta-Selective Inhibitors, Radium 223 Dichloride and other variants, androgen receptor antagonist, CYP17A1 inhibitors, LHRH antagonist, LHRH analogs, Cyclophosphamide, cabazitaxel, Docetaxel, PULP vaccines like Sipuleucel-T, Prostvac, Provange, PSCA, whole cell vaccines and others, therapeutics against PULP surface antigens, Cisplatin, Bispecific antibody-CD3 and ADAM17, pTVG-HP Plasmid DNA Vaccine and other similar vaccines, Tisotumab Vedotin, DCVAC/PCa, GX301, GVAX-PCa and Denosumab. 
     Chemotherapeutic drugs and anti-cancer agents that can be administered in combination with an anti-CLEC2D antibodies or compositions of the disclosure include, but are not restricted to alkylating agents, antimetabolites, plant alkaloids, vinca alkaloids, mitotic inhibitors, antitumor antibiotics, platinum based anti-neoplastics, topoisomerase inhibitors and protein kinase inhibitors. Exemplary alkylating agents comprise busulfan, cyclophosphamide and temozolamide. Exemplary antimetabolites comprise 5-fluorouracil (5-FU), 6-mercaptopurine (6-MP), Capecitabine (Xeloda) and Gemcitabine. Exemplary anti tumor antibiotics comprise Dactinomycin, Bleomycin, Daunorubicin and Doxorubicin. Exemplary platinum based anti-neoplastics comprise Cisplatin and Carboplatin. Exemplary topoisomerase inhibitors comprise Etoposide, Irinotecan and Topotecan. Exemplary mitotic inhibitors comprise taxanes (e.g., Paclitaxel, Docetaxel), vinca alkaloids (Vinblastine, Vincristine, Vinorelbine) and colchicine. Additional chemotherapeutic agents comprise methotrexate. 
     Therapeutic agents that can be administered in combination with an anti-CLEC2D antibody or composition comprising the same of the disclosure include, but are not restricted to Orteronel, Geldanamycin, Cabozantinib, Alpharadin, 177Lu-J591, Mitoxantrone, Viamet, CFG920, Galeteron, Olaparib, ADXS-PSA, Taxotere, Gonax, Decapeptyl, Lupron, Vantas, Casodex, Zoladex, Eligard, Leuplin, Firmagon, mitoxantrone, Emcyt, lanreotide, Zaltrap, custirsen sodium and Sprycel. 
     The Anti-CLEC2D antibodies of the disclosure can be used in combination with monoclonal antibodies or fragments thereof, therapeutic biologics, small molecules or chemical agents that inhibit or modulate the following targets: Cluster of Differentiation 19 (CD19), Programmed cell death protein 1 (PD1), Programmed death-ligand 1 (PDL1), human epidermal growth factor receptor 2 (Her2), Signal transducer and activator of transcription 3 (STAT3), cluster of differentiation 152 (CTLA4), New York esophageal squamous cell carcinoma 1 (NYESO1), B-cell maturation antigen (BCMA), indoleamine 2,3-dioxygenase (IDO), Neo antigens, Colony Stimulating Factor 1 Receptor (CSF1R), B-lymphocyte surface antigen B1 (CD20), Wilms tumor protein (WT1), Cluster of Differentiation 47 (CD47), Mucin 1, cell surface associated (MUC1), TNF receptor superfamily member 9 (4-1BB), disialoganglioside GD2, Adenosine A2a Receptor (ADORA2A), nterferon-alpha/beta receptor alpha chain (IFNAR1), Toll-like receptor 7 (TLR7), Cluster of differentiation 40 (CD40), Mesothelin, epidermal growth factor receptor (EGFR), Histone deacetylase 1 (HDAC1), interleukin-2 receptor (IL2R), Telomerase reverse transcriptase (TERT), Toll-like receptor (TLR), Siglec-3 (CD33), Lymphocyte-activation gene 3 (LAG3), Tumor necrosis factor receptor superfamily, member 4 (OX40), C—X—C chemokine receptor type 4 (CXCR4), Histone deacetylase 6 (HDAC6), prostate-specific membrane antigen (PSMA), Epstein-Barr virus (EBV), granulocyte-macrophage colony-stimulating factor receptor (GMCSFR), Toll-like receptor 9 (TLR9), interleukin-3 receptor (CD123), Stimulator of interferon genes (STING), T-cell immunoreceptor with Ig and ITIM domains (TIGIT), T-cell immunoglobulin and mucin-domain containing-3 (TIM3), Toll-like receptor 4 (TLR4), human papillomavirus gene E6 (HPV-E6), 5′-nucleotidase (CD73), Carcinoembryonic Antigen Related Cell Adhesion Molecule 5 (CEACAM5), Survivin, Cluster of differentiation 3 (CD3), cyclic ADP ribose hydrolase (CD38), glucocorticoid-induced TNFR-related protein (GITR), human papillomavirus E7 oncoprotein (HPVE7), Interleukin 21 Receptor (IL21R), CD137), cluster of differentiation-22 (CD22), tumor necrosis factor receptor superfamily member 8 (CD30), Glypican-3 (GPC3), Beta Catenin, fms-like tyrosine kinase 3 (FLT3), janus kinase 2 (JAK2), Epithelial cell adhesion molecule (EPCAM), Melanoma-Associated Antigen 3 (MAGE-A3), Toll-like receptor 3 (TLR3), human papillomavirus (HPV), K-ras (KRAS), Receptor Tyrosine Kinase Like Orphan Receptor 1 (ROR1), Ubiquitin Specific Peptidase 7 (USP7), Trophoblast glycoprotein (5T4), Interleukin-2 receptor alpha chain (CD25), Cytomegalovirus (CMV), C—X—C Motif Chemokine Ligand 12 (CXCL12), granulocyte colony-stimulating factor receptor (GCSFR), killer cell lectin like receptor K1 (NKG2D), premelanosome protein (PMEL), Preferentially Expressed Antigen In Melanoma (PRAME), V-domain Ig suppressor of T cell activation (VISTA), C-C Motif Chemokine Receptor 4 (CCR4), cluster of differentiation 46 (CD46), Macrophage Stimulating Protein Receptor (CDw136), cyclooxygenase-2 (COX2), SLAM family member 7 (CS1), C—X—C Motif Chemokine Receptor 1 (CXCR1), epidermal growth factor receptor variant III (EGFRvIII), p96, glucocorticoid receptor (GR), Inducible T-cell costimulator (ICOS), Insulin-like growth factor 1 (IGF1), interleukin-5 receptor (IL5R), janus kinase 1 (JAK1), prostate specific antigen (PSA), Signal transducer and activator of transcription 5 (STATS), Transforming Growth Factor Beta Receptor 2 (TGFBR2), Vascular endothelial growth factor (VEGF), Anaplastic lymphoma kinase (ALK), alpha-galactosidase A (Alpha-gal), Cluster of Differentiation 276 (B7-H3), C-C Motif Chemokine Receptor 1 (CCR1), C-C chemokine receptor type 2 (CCR2), CD27 molecule (CD27), ectonucleoside triphosphate diphosphohydrolase 1 (CD39), carcinoembryonic antigen (CEA), Gelactin-3, Interleukin 13 Receptor Subunit Alpha 2 (IL13RA2), Interleukin 6 (IL6), Interleukin 6 Receptor (IL6R), Interleukin 1 Receptor Associated Kinase 4 (IRAK4), MER Proto-Oncogene, Tyrosine Kinase (MERTK), Macrophage migration inhibitory factor (MIF), Protein melan-A (MLANA), Prostaglandin E Receptor 4 (PTGER4), distal-less homeobox 3 (TDO), transforming growth factor beta 1 (TGFB, TGFB1), toll like receptor 2 (TLR2), tumor necrosis factor (TNF), ADORA2B, alpha fetoprotein (AFP), angiopoietin 1 (ANG1), BTLA, prominin 1 (CD133), neural cell adhesion molecule 1 (CD56), CD70 molecule (CD70), carcinoembryonic antigen related cell adhesion molecule 6 (CEACAM6), C-type lectin domain family 12 member A (CLEC12A), C—X—C motif chemokine receptor 2 (CXCR2), fibroblast activation protein alpha (FAP), histone deacetylases (HDAC), interferon alpha and beta receptor subunit 1 (IFNAR), interferon gamma receptor 1 (IFNGR1), interleukin 17 receptor A (IL17R), Janus kinase (JAK), mucin 16, cell surface associated (MUC16), mitogen activated protein kinase (P38), tumor protein p53 (p53), DExD/H-box helicase 68 (RIG1), RAR related orphan receptor C (RORC), signal regulatory protein alpha (SIRPA), transforming growth factor beta receptor 1 (TGFBR1), dopachrome tautomerase (TRP2), adenosine A3 receptor (ADORA3), Brachyury, C-C motif chemokine receptor 7 (CCR7), syndecan 1 (CD138), L1 cell adhesion molecule (CD171), fucosyltransferase 3 (Lewis blood group) (CD174), Fc fragment of IgG receptor IIa (CD32), C-X3-C motif chemokine receptor 1 (CX3CR1), FPHA2, folate receptor 1 (FOLR1), beta-1,3-N-acetylgalactosaminyltransferase 1 (globoside blood group) (GloboH), isocitrate dehydrogenase (NADP(+)) 1, cytosolic (IDH1), interleukin 2 receptor subunit beta (IL2rB), Janus kinase 3 (JAK3), prostate stem cell antigen (PSCA), RAS, transforming growth factor beta 2 (TGFB2), toll like receptor 8 (TLR8), acid phosphatase, prostate (ACPP), dipeptidyl peptidase 4 (ADABP), ADAM metallopeptidase domain 17 (ADAM17), androgen receptor (AR), ATRT, AXL receptor tyrosine kinase (AXL), V-set domain containing T cell activation inhibitor 1 (B7-H4), CA19-9, integrin subunit alpha M (CD11b), Fc fragment of IgG receptor Ma (CD16), CD16a, CD200 molecule (CD200), CD28 molecule (CD28), CD52 molecule (CD52), CD7 molecule (CD7), CD80 molecule (CD80), complement C5a receptor 1 (CD88), cadherin 3 (CDH3), CECAM1, cytochrome c oxidase subunit II (COX2), CCCTC-binding factor like (CTCFL), C—X—C motif chemokine receptor 5 (CXCR5), atypical chemokine receptor 3 (CXCR7), E1a, Gastrin, Graves disease, susceptibility to, X-linked (GD3), Gelactin-1, colony stimulating factor 2 (GMCSF), HBV, HLA-A2, HLA-DR, human papillomavirus (HPV) E6/7, HPV L2, interferon alpha and beta receptor subunit 2 (IFNAR2), insulin like growth factor 1 receptor (IGF1R), interleukin 12 (IL12), interleukin 1 beta (IL1B), interleukin 7 receptor (IL7R), C—X—C motif chemokine ligand 8 (IL8), killer cell immunoglobulin like receptor, two Ig domains and long cytoplasmic tail 1 (KIR2DL1), killer cell immunoglobulin like receptor, two Ig domains and long cytoplasmic tail 3 (KIR2DL3), LXR, CD244 molecule (2B4), Mage family member A (MAGE-A), MAGE family member A1 (MAGE-A1), MAGE family member A4 (MAGE-A4), X-linked inhibitor of apoptosis (MiHA), killer cell lectin like receptor C1 (NKG2A), natural cytotoxicity triggering receptor 1 (NKp46), nuclear receptor subfamily 2 group F member 6 (NR2F6), PTTG1 interacting protein (PBF), sperm adhesion molecule 1 (SPAM1), signal transducer and activator of transcription 1 (STAT1), toll like receptor 5 (TLR5), peroxiredoxin 2 (TSA), tyrosine kinase 2 (TYK2), kinase insert domain receptor (VEGFR2), 5′ Nucleotidase, ATP binding cassette subfamily B member 5 (ABCB5), ADAM metallopeptidase domain 9 (ADAMS), Adenosine, ADP, metadherin (AEG1), absent in melanoma 2 (AIM2), Alpha-lactalbumin, anti-Mullerian hormone receptor type 2 (AMHR2), angiopoietin 2 (ANG2), Angiogenesis, aspartate beta-hydroxylase (ASPH), natural killer cell cytotoxicity receptor 3 ligand 1 (B7-H6), TNF receptor superfamily member 13C (BAFF-R), poly(ADP-ribose) polymerase family member 9 (Ball), BRCA1 associated RING domain 1 (BARD1), BCL2 apoptosis regulator (BCL2), POU class 2 associating factor 1 (BOB-1), BTE6-1X-8b, BTE6-X-15-7, KIT proto-oncogene, receptor tyrosine kinase (cKIT), carbonic anhydrase 9 (CA9), Carbohydrate antigens, cannabinoid receptor 2 (CB2), Cbl proto-oncogene B (CBLB), C-C motif chemokine ligand 20 (CCL20), C-C motif chemokine ligand 3 (CCL3), cyclin B1 (CCNB1), C-C motif chemokine receptor 9 (CCR9), alanyl aminopeptidase, membrane (CD13), interleukin 6 signal transducer (CD130), basigin (Ok blood group) (CD147), poliovirus receptor (CD155), CD160 molecule (CD160), selectin P ligand (CD162), CD200 receptor 1 (CD200R1), complement C3d receptor 2 (CD21), TNF receptor superfamily member 13B (CD267), integrin subunit beta 1 (CD29), CD3e molecule (CD3E), CD4 molecule (CD4), CD44 molecule (Indian blood group) (CD44), integrin subunit alpha V (CD51), intercellular adhesion molecule 1 (CD54), CD8a molecule (CD8), CGEN-XXXX, Claudin 18, Claudin 6, MET proto-oncogene, receptor tyrosine kinase (cMet), coproporphyrinogen oxidase (COX), prostaglandin-endoperoxide synthase 1 (COX-1), cytochrome c oxidase subunit I (COX-1), CPEG4, cereblon (CRBN), cytokine receptor like factor 2 (CRLF2), colony stimulating factor 1 (CSF1), phosphate cytidylyltransferase 1, choline, alpha (CTA), C—X—C motif chemokine ligand 1 (CXCL1), C—X—C motif chemokine receptor 3 (CXCR3), deoxycytidine kinase (DCK), dickkopf WNT signaling pathway inhibitor 1 (DKK1), delta like canonical Notch ligand 3 (DLL3), TNF receptor superfamily member 10b (DRS), EBNA3C, epidermal growth factor (EGF), C-type lectin domain containing 14A (EGFR5), eukaryotic translation initiation factor 2 alpha kinase 3 (EIF2AK3), ELVAL4, EPH receptor A3 (EPHA3), epidermal growth factor receptor pathway substrate 8 (EPS8), ERG, Fc fragment of IgM receptor (FAIM-3), fibroblast growth factor 2 (FGF2), fms related tyrosine kinase 3 (FLT3), fibronectin 1 (FN1), folate receptor 1 (FOLR), forkhead box M1 (FOXM1), follicle stimulating hormone receptor (FSHR), Galectin 3, N-acetylgalactosaminyltransferase (GalNAc), leucine rich repeat containing 32 (GARP), GC vitamin D binding protein (GC), Gelactin 9, Gelactin1/3/9, GM2, gonadotropin releasing hormone receptor (GNRHR), glutamyl aminopeptidase (GP160), golgi membrane protein 1 (GP73), glycoprotein A33 (gpA33), H3.3K27M, DEAD-box helicase 43 (HAGE), histone deacetylase 2 (HDAC2), histone deacetylase 8 (HDAC8), Hemagglutinin, erb-b2 receptor tyrosine kinase 3 (HER3), hypoxia inducible lipid droplet associated (HILPDA), chondroitin sulfate proteoglycan 4 (HMWMAA), HP59, HPV16, HPV11, heat shock protein family H (Hsp110) member 1 (HSP105), heat shock protein family D (Hsp60) member 1 (HSP65), heat shock protein family A (Hsp70) member 4 (HSP70), TNF receptor superfamily member 14 (HVEM), Hyaluronan, indoleamine 2,3-dioxygenase 1(IDO1), interferon gamma (IFNG), interferon gamma receptor 1 (IFNGR), interferon gamma receptor 2 (IFNGR2), insulin like growth factor 2 (IGF2), insulin like growth factor binding protein 2(IGFBP2), IGK2, interleukin 10 (IL10), interleukin 10 receptor subunit alpha (IL10RA), interleukin 12 receptor subunit beta 1 (IL12RB1), interleukin (IL13), interleukin 13 receptor subunit alpha 2 (IL13R), interleukin 13 receptor subunit alpha 1 (IL13RA1), interleukin 15 (IL15), interleukin 15 receptor subunit alpha (IL15RA), interleukin 17A (IL17 IL17A), interleukin 17B (IL17B), interleukin 1 receptor type 1 (IL1R1), interleukin 1 receptor accessory protein (IL1R3), interleukin 21 receptor (IL21R), interleukin 27 receptor subunit alpha (IL27R), interleukin 2 receptor subunit alpha (IL2RA), IL35, interleukin 9 receptor (IL9R), Integrin beta 7, interleukin 1 receptor associated kinase 1 (IRAK1), integrin subunit beta 5 (ITGB5), Kappa Myeloma antigen, kinesin family member 20A (KIF20A), killer cell immunoglobulin like receptor, two Ig domains and long cytoplasmic tail 2 (KIR2DL2), Kynurenine, Lambda myeloma antigen, lysosomal associated membrane protein 3 (LAMP), LLO, nuclear receptor subfamily 1 group H member 3 (LXRA), nuclear receptor subfamily 1 group H member 2 (LXRB), MAGEA10 MAGE family member A10 (MAGE-A10), MAGEA6 MAGE family member A6 (MAGE-A6), MAGEC2 MAGE family member C2 (MAGE-C2), Mammaglobin A, mitogen-activated protein kinase (MAPK), Mas receptor, interferon induced with helicase C domain 1 (MDA5), MG7, major histocompatibility complex II (MHCII), MIC, MHC class I polypeptide-related sequence A (MICA), MHC class I polypeptide-related sequence (MICB), matrix metallopeptidase 11 (MMP-11), motile sperm domain containing 2 (MOSPD2), Multidrug resistance-associated protein-1 (MRP1), MRP3765, muGNTP01, major vault protein (MVP), MYB proto-oncogene, transcription factor (MYB), MYB proto-oncogene like 2 (MYBL2), Myeloblastin, MYCN proto-oncogene, bHLH transcription factor (N-myc), nuclear factor of activated T cells (NFAT), NLR family pyrin domain containing 3 (NLRP3), Oncofetal antigen, purinergic receptor P2X 5 (P2RX5), p38 map kinase, phosphoinositide-3-kinase regulatory subunit 3 (P55), PAM4, regenerating family member 3 alpha (PAP), PAS domain containing repressor 1 (PASD1), protocadherin 18 (PCDH18), programmed cell death 1 ligand 2 (PDL2), POTE ankyrin domain family member D (POTE), protein phosphatase 5 catalytic subunit (PPT), prostaglandin E receptor 2 (PTGER2), PVR related immunoglobulin domain containing (PVRIG), RBL001, ras homolog family member C (RhoC), receptor tyrosine kinase like orphan receptor 2 (ROR2), SEREX, SIM bHLH transcription factor 2 (SIM2), somatostatin receptor 2 (SSTR2), SSX family member 2 (SSX2), sterol O-acyltransferase 1 (STAT), eukaryotic translation elongation factor 1 alpha 2 (STn), mRNA cap guanine-N7 methyltransferase (TAG72), TAMA, TASTD2, TD02, transcription factor Dp family member 3 (TFDP3), Thymidylate synthase, DNA topoisomerase I (TOP1), T cell receptor beta constant 1 (TRBC1), T cell receptor beta constant 2 (TRBC2), Tryptophan, thyroid stimulating hormone receptor (TSHR), TNF superfamily member 12 (TWEAK), Tyrosine, lymphocyte antigen 6 family member K (URLC10), retroelement silencing factor 1 (UTA2-1), fms related tyrosine kinase 1 (VEGFR1), V-set and immunoglobulin domain containing 4 (VSIG-4), X antigen family, member 1 (XAGE1), zona pellucida glycoprotein 3 (ZP3), STEAP family member 1 (STEAP1), or TNF superfamily member 11 (RANKL). 
     In some embodiments, the anti-CLEC2D antibodies or compositions of the disclosure are administered in combination with an immune checkpoint inhibitor, include, but are not limited to CTLA4, PPP2CA, PPP2CB, PTPN6, PTPN22, PDCD1, ICOS (CD278), PDL1, KIR, LAG3, HAVCR2, BTLA, CD160, TIGIT, CD96, CRTAM, LAIR1, SIGLEC7, SIGLEC9, CD244 (2B4), TNFRSF10B, TNFRSF10A, CASP8, CASP10, CASP3, CASP6, CASP7, FADD, FAS, TGFBRII, TGFRBRI, SMAD2, SMAD3, SMAD4, SMAD10, SKI, SKIL, TGIF1, IL10RA, IL10RB, HMOX2, IL6R, IL6ST, EIF2AK4, CSK, PAG1, SIT1, FOXP3, PRDM1, BATF, VISTA, GUCY1A2, GUCY1A3, GUCY1B2, GUCY1B3, MT1, MT2, CD40, OX40, CD137, GITR, CD27, SHP-1, TIM-3, CEACAM-1, CEACAM-3, or CEACAM-5. In some embodiments, anti-CLEC2D antibodies or compositions of the disclosure are administered in combination with an immune checkpoint inhibitor. Exemplary immune checkpoint genes and therapeutic targets include programmed cell death 1 (PD1), PD-L1, CLTA-4, T cell immunoglobulin and mucin 3 (TIM-3) and lymphocyte activating 3 (LAG-3). In some embodiments, the immune checkpoint inhibitor is a therapeutic antibody that binds to and inhibits PD1, PD-L1 (Programmed death-ligand 1), CLTA-4 or TIM3. Exemplary PD1 inhibitors comprise Pembrolizumab, Nivolumab and Cemiplimab. Exemplary PD-L1 inhibitors comprise Atezolizumab, Avelumab and Durvalumab. Exemplary CLTA-4 inhibitors comprise Ipilimumab. 
     In some embodiments, the anti-CLEC2D antibodies or compositions of the disclosure are administered in combination with a kinase inhibitor, wherein the kinase inhibitor inhibits BCR-Abl, B-raf, BTK, CDK family, c-Met, EGFR family, JAK family, MEK ½, PDGFR alpha/beta, RET, Src family, or VEGFR family kinases. In some embodiments, the kinase inhibitor as disclosed herein, is a small kinase molecule inhibitor. In some embodiments, the the kinase inhibitor as disclosed herein, is a therapeutic antibody or an antagonistic antibody. In some embodiments, the kinase inhibitor as disclosed herein, is a Crizotinib, Ceritinib, Alectinib, Brigatinib, Bosutinib, Dasatinib, Imatinib, Nilotinib, Ponatinib, Vemurafenib, Dabrafenib, Ibrutinib, Palbociclib, Sorafenib, Ribociclib, Crizotinib, Cabozantinib, Gefitinib, Erlotinib, Lapatinib, Vandetanib, Afatinib, Osimertinib, Ruxolitinib, Tofacitinib, Trametinib, Axitinib, Gefitinib, Imatinib, Lenvatinib, Nintedanib, Pazopanib, Regorafenib, Sorafenib, Sunitinib, Vandetanib, Bosutinib, Dasatinib, Ponatinib, Vandetanib, Axitinib, Lenvatinib, Nintedanib, Regorafenib, Pazopanib, Sorafenib, Sunitinib, or a combination thereof. 
     In some embodiments, the anti-CLEC2D antibodies or compositions of the disclosure are administered in combination with an anti-CD20 antibody. In some embodiments, the anti-CLEC2D antibodies or compositions of the disclosure are administered in combination with an anti-CD20 antibody, a TNF-receptor antagonist, an anti-TNF-α, or a combination thereof, e.g., for treatment of rheumatoid arthritis. In some embodiments, the anti-CLEC2D antibodies or compositions of the disclosure are administered in combination with anti-CD11a, e.g., for treatment of psoriais, In some embodiments, the anti-CLEC2D antibodies or compositions of the disclosure are administered in combination with IFN-γ, e.g., for treatment of multiple sclerosis. In some embodiments, the anti-CLEC2D antibodies or compositions of the disclosure are administered in combination with TNF-α, e.g., for treatment of ulcerative colitis. In some embodiments, the anti-CLEC2D antibodies or compositions of the disclosure are administered in combination with Infliximab or Natalizumab, e.g., for treatment of Crohn&#39;s disease. 
     In some embodiments, the anti-CLEC2D antibodies or compositions of the disclosure are administered in combination with a multispecific antibody directed against any combination of immune check points gene product and/or target antigens associated with cancer. In some embodiments, the anti-CLEC2D antibodies or compositions of the disclosure are administered in combination with a bispecific antibody directed against any combination of immune check points gene product and/or target antigens associated with cancer. 
     In some embodiments, the anti-CLEC2D antibodies or compositions of the disclosure are administered in combination with a bispecific antibody directed against an immune check point protein selected from the group consisting of include programmed cell death 1 (PD1), PD-L1, CLTA-4, T cell immunoglobulin and mucin 3 (TIM-3) and lymphocyte activating 3 (LAG-3). In some embodiments, the immune checkpoint inhibitor is a therapeutic antibody that binds to and inhibits PD1, PD-L1 (Programmed death-ligand 1), CLTA-4 or TIM3. 
     In some embodiments, the anti-CLEC2D antibodies or compositions of the disclosure are administered in combination with a bispecific antibody directed against a tumor antigen selected from the group consisting of: B cell maturation antigen (BCMA); PSA (prostate-specific antigen); prostatespecific membrane antigen (PSMA); PSCA (Prostate stem cell antigen); Tyrosine-protein kinase transmembrane receptor ROR1; fibroblast activation protein (FAP); Tumor-associated glycoprotein 72 (TAG72); Carcinoembryonic antigen (CEA); Epithelial cell adhesion molecule (EPCAM); Mesothelin; Human Epidermal growth factor Receptor 2 (ERBB2 (Her2/neu)); Prostate; Prostatic acid phosphatase (PAP); elongation factor 2 mutant (ELF2M); Insulin-like growth factor 1 receptor (IGF-1R); gplOO; BCR-ABL (breakpoint cluster region-Abelson); tyrosinase; New York esophageal squamous cell carcinoma 1 (NY-ESO-1); k-light chain, LAGE (L antigen); MAGE (melanoma antigen); Melanoma-associated antigen 1 (MAGE-A1); MAGE A3; MAGE A6; legumain; Human papillomavirus (HPV) E6; HPVE7; prostein; survivin; PCTA1 (Galectin 8); Melan-A/MART-1; Ras mutant; TRP-1 (tyrosinase related protein 1, or gp75); Tyrosinase-related Protein 2 (TRP2); TRP-2/INT2 (TRP-2/intron 2); RAGE (renal antigen); receptor for advanced glycation end products 1 (RAGED; Renal ubiquitous 1, 2 (RU1, RU2); intestinal carboxyl esterase (iCE); Heat shock protein 70-2 (HSP70-2) mutant; thyroid stimulating hormone receptor (TSHR); CD123; CD171; CD19; CD20; CD22; CD26; CD30; CD33; CD44v7/8 (cluster of differentiation 44, exons 7/8); CD53; CD92; CD100; CD148; CD150; CD200; CD261; CD262; CD362; CS-1 (CD2 subset 1, CRACC, SLAMF7, CD319, and 19A24); C-type lectin-like molecule-1 (CLL-1); ganglioside GD3 (aNeu5Ac(2-8)aNeu5Ac(2-3)bDGalp(1-4)bDG1cp(11)Cer); Tn antigen (Tn Ag); Fms-Like Tyrosine Kinase 3 (FLT3); CD38; CD138; CD44v6; B7H3 (CD276); KIT (CD1 17); Interleukin-13 receptor subunit alpha-2 (IL-13Ra2); Interleukin 11 receptor alpha (IL-11Ra); prostate stem cell antigen (PSCA); Protease Serine 2 1 (PRSS21); vascular endothelial growth factor receptor 2 (VEGFR2); Lewis(Y) antigen; CD24; Platelet derived growth factor receptor beta (PDGFR-beta); stage-specific embryonic antigen-4 (SSEA-4); Mucin 1, cell surface associated (MUC1); mucin 16 (MUC1 6); epidermal growth factor receptor (EGFR); epidermal growth factor receptor variant III (EGFRvIII); neural cell adhesion molecule (NCAM); carbonic anhydrase IX (CAIX); Proteasome (Prosome, Macropain) Subunit, Beta Type, 9 (LMP2); ephrin type-A receptor 2 (EphA2); Ephrin B2; Fucosyl GM1; sialyl Lewis adhesion molecule (sLe); ganglioside GM3 (aNeu5Ac(2-3)bDGalp(1-4)bDG1cp(1-1)Cer); TGS5; high molecular weight-melanoma-associated antigen (HMWMAA); o-acetyl-GD2 ganglioside (OAcGD2); Folate receptor alpha; Folate receptor beta; tumor endothelial marker 1 (TEM1/CD248); tumor endothelial marker 7-related (TEM7R); claudin 6 (CLDN6); G protein coupled receptor class C group 5, member D (GPRCSD); chromosome X open reading frame 6 1 (CXORF61); CD97; CD179a; anaplastic lymphoma kinase (ALK); Poly sialic acid; placenta specific 1 (PLAC1); hexasaccharide portion of globoH glycoceramide (GloboH); mammary gland differentiation antigen (NY-BR-1); uroplakin 2 (UPK2); Hepatitis A virus cellular receptor 1 (HAVCR1); adrenoceptor beta 3 (ADRB3); pannexin 3 (PANX3); G protein-coupled receptor 20 (GPR20); lymphocyte antigen 6 complex, locus K 9 (LY6K); Olfactory receptor 51E2 (OR51E2); TCR Gamma Alternate Reading Frame Protein (TARP); Wilms tumor protein (WT1); ETS translocation-variant gene 6, located on chromosome 12p (ETV6-AML); sperm protein 17 (SPA17); X Antigen Family, Member 1A (XAGE1); angiopoietin-binding cell surface receptor 2 (Tie 2); CT (cancer/testis (antigen)); melanoma cancer testis antigen-1 (MAD-CT-1); melanoma cancer testis antigen-2 (MAD-CT-2); Fos-related antigen 1; p53; p53 mutant; human Telomerase reverse transcriptase (hTERT); sarcoma translocation breakpoints; melanoma inhibitor of apoptosis (ML-IAP); ERG (transmembrane protease, serine 2 (TMPRSS2) ETS fusion gene); NAcetyl glucosaminyl-transferase V (NA17); paired box protein Pax-3 (PAX3); Androgen receptor; Cyclin B1; Cyclin Dl; v-myc avian myelocytomatosis viral oncogene neuroblastoma derived homolog (MYCN); Ras Homolog Family Member C (RhoC); Cytochrome P450 1B1 (CYP1B1); CCCTC-Binding Factor (Zinc Finger Protein)-Like (BORIS); Squamous Cell Carcinoma Antigen Recognized By T Cells-1 or 3 (SART1, SART3); Paired box protein Pax-5 (PAX5); proacrosin binding protein sp32 (OY-TES1); lymphocyte-specific protein tyrosine kinase (LCK); A kinase anchor protein 4 (AKAP-4); synovial sarcoma, X breakpoint-1, -2, -3 or -4 (SSX1, SSX2, SSX3, SSX4); CD79a; CD79b; CD72; Leukocyte-associated immunoglobulin-like receptor 1 (LAIR1); Fc fragment of IgA receptor (FCAR); Leukocyte immunoglobulin-like receptor subfamily A member 2 (LILRA2); CD300 molecule-like family member f (CD300LF); C-type lectin domain family 12 member A (CLEC12A); bone marrow stromal cell antigen 2 (BST2); EGF-like module containing mucin-like hormone receptor-like 2 (EMR2); lymphocyte antigen 75 (LY75); Glypican-3 (GPC3); Fc receptor-like 5 (FCRL5); mouse double minute 2 homolog (MDM2); livin; alphafetoprotein (AFP); transmembrane activator and CAML Interactor (TACI); B-cell activating factor receptor (BAFF-R); V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS); immunoglobulin lambda-like polypeptide 1 (IGLL1); 707-AP (707 alanine proline); ART-4 (adenocarcinoma antigen recognized by T4 cells); BAGE (B antigen; b-catenin/m, bcatenin/mutated); CAMEL (CTL-recognized antigen on melanoma); CAP1 (carcinoembryonic antigen peptide 1); CASP-8 (caspase-8); CDC27m (cell-division cycle 27 mutated); CDK4/m (cycline-dependent kinase 4 mutated); Cyp-B (cyclophilin B); DAM (differentiation antigen melanoma); EGP-2 (epithelial glycoprotein 2); EGP-40 (epithelial glycoprotein 40); Erbb 2, 3, 4 (erythroblastic leukemia viral oncogene homolog-2, -3, 4); FBP (folate binding protein); fAchR (Fetal acetylcholine receptor); G250 (glycoprotein 250); GAGE (G antigen); GnT-V (Nacetylglucosaminyltransferase V); HAGE (helicose antigen); ULA-A (human leukocyte antigen-A); HST2 (human signet ring tumor 2); KIAA0205; KDR (kinase insert domain receptor); LDLR/FUT (low density lipid receptor/GDP L-fucose: b-D-galactosidase 2-a-L fucosyltransferase); LICAM (LI cell adhesion molecule); MC1R (melanocortin 1 receptor); Myosin/m (myosin mutated); MUM-1, -2, -3 (melanoma ubiquitous mutated 1, 2, 3); NA88-A (NA cDNA clone of patient M88); KG2D (Natural killer group 2, member D) ligands; oncofeta antigen (h5T4); pi 90 minor bcr-abl (protein of 190KD bcr-abl); Pml/RARa (promyelocytic leukaemia/retinoic acid receptor a); PRAME (preferentially expressed antigen of melanoma); SAGE (sarcoma antigen); TEL/AML1 (translocation Ets-family leukemia/acute myeloid leukemia 1); TPI/m (triosephosphate isomerase mutated); CD70; and any combination thereof. 
     In some embodiments, the anti-CLEC2D antibodies or compositions of the disclosure are administered in combination with a drug or therapeutic agent including but not limited to Mycophenolate, Azathioprine, Cyclophosphamide, Pirfenidone, Nintedanib, Lansoprazole (Prevacid 24HR Omeprazole (Prilosec OTC) and Pantoprazole (protonix), or a combination thereof. 
     In some embodiments, the anti-CLEC2D antibodies or compositions of the disclosure are administered in combination with a cytokine or chemokine including but not limited to interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), granulocyte macrophage colony-stimulating factor (GM-CSF), IL-8, vascular endothelial growth factor (VEGF), stromal cell-derived factor-1, and interferon gamma-inducible protein-10 (IP-10), chemokines (CCL1, CCL2, CCL3, CCL4, CCL5, and CXCL8) or a combination thereof. 
     In some embodiments, anti-CLEC2D antibodies or compositions of the disclosure are administered in combination with an adoptive cell therapy. In some embodiments, the adoptive cell therapy is autologous. In some embodiments, the adoptive cell therapy is allogenic. In some embodiments, the adoptive cell therapy comprises an immune cell such as a T cell or an NK cell. In some embodiments, the adoptive cell therapy comprises a chimeric antigen receptor T cell (CAR-T) or CAR-NK therapy. 
     In some embodiments, the CLEC2D antibodies or compositions of the disclosure are administered in combination with adoptive cell therapy comprising a chimeric antigen receptor T cell (CAR-T) directed against target antigens associated with a solid tumor. 
     In some embodiments, the CLEC2D antibodies or compositions of the disclosure are administered in combination with adoptive cell therapy comprising a chimeric antigen receptor T cell (CAR-T) directed against target antigens associated with cancer, including but not limited to acute lymphoblastic leukemia, diffuse large b-cell lymphoma, follicular lymphoma, chronic lymphocytic leukemia, multiple myeloma, and others. 
     In some embodiments, the CLEC2D antibodies or compositions of the disclosure are administered in combination with adoptive cell therapy comprising a chimeric antigen receptor T cell (CAR-T) directed against a second antigen is a tumor antigen selected from the group consisting of: B cell maturation antigen (BCMA); PSA (prostate-specific antigen); prostatespecific membrane antigen (PSMA); PSCA (Prostate stem cell antigen); Tyrosine-protein kinase transmembrane receptor ROR1; fibroblast activation protein (FAP); Tumor-associated glycoprotein 72 (TAG72); Carcinoembryonic antigen (CEA); Epithelial cell adhesion molecule (EPCAM); Mesothelin; Human Epidermal growth factor Receptor 2 (ERBB2 (Her2/neu)); Prostate; Prostatic acid phosphatase (PAP); elongation factor 2 mutant (ELF2M); Insulin-like growth factor 1 receptor (IGF-1R); gp100; BCR-ABL (breakpoint cluster region-Abelson); tyrosinase; New York esophageal squamous cell carcinoma 1 (NY-ESO-1); k-light chain, LAGE (L antigen); MAGE (melanoma antigen); Melanoma-associated antigen 1 (MAGE-A1); MAGE A3; MAGE A6; legumain; Human papillomavirus (HPV) E6; HPVE7; prostein; survivin; PCTA1 (Galectin 8); Melan-A/MART-1; Ras mutant; TRP-1 (tyrosinase related protein 1, or gp75); Tyrosinase-related Protein 2 (TRP2); TRP-2/INT2 (TRP-2/intron 2); RAGE (renal antigen); receptor for advanced glycation end products 1 (RAGED; Renal ubiquitous 1, 2 (RU1, RU2); intestinal carboxyl esterase (iCE); Heat shock protein 70-2 (HSP70-2) mutant; thyroid stimulating hormone receptor (TSHR); CD123; CD171; CD19; CD20; CD22; CD26; CD30; CD33; CD44v7/8 (cluster of differentiation 44, exons 7/8); CD53; CD92; CD100; CD148; CD150; CD200; CD261; CD262; CD362; CS-1 (CD2 subset 1, CRACC, SLAMF7, CD319, and 19A24); C-type lectin-like molecule-1 (CLL-1); ganglioside GD3 (aNeu5Ac(2-8)aNeu5Ac(2-3)bDGalp(1-4)bDG1cp(11)Cer); Tn antigen (Tn Ag); Fms-Like Tyrosine Kinase 3 (FLT3); CD38; CD138; CD44v6; B7H3 (CD276); KIT (CD1 17); Interleukin-13 receptor subunit alpha-2 (IL-13Ra2); Interleukin 11 receptor alpha (IL-11Ra); prostate stem cell antigen (PSCA); Protease Serine 2 1 (PRSS21); vascular endothelial growth factor receptor 2 (VEGFR2); Lewis(Y) antigen; CD24; Platelet derived growth factor receptor beta (PDGFR-beta); stage-specific embryonic antigen-4 (SSEA-4); Mucin 1, cell surface associated (MUC1); mucin 16 (MUC1 6); epidermal growth factor receptor (EGFR); epidermal growth factor receptor variant III (EGFRvIII); neural cell adhesion molecule (NCAM); carbonic anhydrase IX (CAIX); Proteasome (Prosome, Macropain) Subunit, Beta Type, 9 (LMP2); ephrin type-A receptor 2 (EphA2); Ephrin B2; Fucosyl GM1; sialyl Lewis adhesion molecule (sLe); ganglioside GM3 (aNeu5Ac(2-3)bDGalp(1-4)bDG1cp(1-1)Cer); TGS5; high molecular weight-melanoma-associated antigen (HMWMAA); o-acetyl-GD2 ganglioside (OAcGD2); Folate receptor alpha; Folate receptor beta; tumor endothelial marker 1 (TEM1/CD248); tumor endothelial marker 7-related (TEM7R); claudin 6 (CLDN6); G protein coupled receptor class C group 5, member D (GPRCSD); chromosome X open reading frame 6 1 (CXORF61); CD97; CD179a; anaplastic lymphoma kinase (ALK); Poly sialic acid; placenta specific1 (PLAC1); hexasaccharide portion of globoH glycoceramide (GloboH); mammary gland differentiation antigen (NY-BR-1); uroplakin 2 (UPK2); Hepatitis A virus cellular receptor 1 (HAVCR1); adrenoceptor beta 3 (ADRB3); pannexin 3 (PANX3); G protein-coupled receptor 20 (GPR20); lymphocyte antigen 6 complex, locus K 9 (LY6K); Olfactory receptor 51E2 (OR51E2); TCR Gamma Alternate Reading Frame Protein (TARP); Wilms tumor protein (WT1); ETS translocation-variant gene 6, located on chromosome 12p (ETV6-AML); sperm protein 17 (SPA17); X Antigen Family, Member 1A (XAGE1); angiopoietin-binding cell surface receptor 2 (Tie 2); CT (cancer/testis (antigen)); melanoma cancer testis antigen-1 (MAD-CT-1); melanoma cancer testis antigen-2 (MAD-CT-2); Fos-related antigen 1; p53; p53 mutant; human Telomerase reverse transcriptase (hTERT); sarcoma translocation breakpoints; melanoma inhibitor of apoptosis (ML-IAP); ERG (transmembrane protease, serine 2 (TMPRSS2) ETS fusion gene); NAcetyl glucosaminyl-transferase V (NA17); paired box protein Pax-3 (PAX3); Androgen receptor; Cyclin B1; Cyclin Dl; v-myc avian myelocytomatosis viral oncogene neuroblastoma derived homolog (MYCN); Ras Homolog Family Member C (RhoC); Cytochrome P450 1B1 (CYP1B1); CCCTC-Binding Factor (Zinc Finger Protein)-Like (BORIS); Squamous Cell Carcinoma Antigen Recognized By T Cells-1 or 3 (SART1, SART3); Paired box protein Pax-5 (PAX5); proacrosin binding protein sp32 (OY-TES1); lymphocyte-specific protein tyrosine kinase (LCK); A kinase anchor protein 4 (AKAP-4); synovial sarcoma, X breakpoint-1, -2, -3 or -4 (SSX1, SSX2, SSX3, SSX4); CD79a; CD79b; CD72; Leukocyte-associated immunoglobulin-like receptor 1 (LAIR1); Fc fragment of IgA receptor (FCAR); Leukocyte immunoglobulin-like receptor subfamily A member 2 (LILRA2); CD300 molecule-like family member f (CD300LF); C-type lectin domain family 12 member A (CLEC12A); bone marrow stromal cell antigen 2 (BST2); EGF-like module containing mucin-like hormone receptor-like 2 (EMR2); lymphocyte antigen 75 (LY75); Glypican-3 (GPC3); Fc receptor-like 5 (FCRL5); mouse double minute 2 homolog (MDM2); livin; alphafetoprotein (AFP); transmembrane activator and CAML Interactor (TACI); B-cell activating factor receptor (BAFF-R); V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS); immunoglobulin lambda-like polypeptide 1 (IGLL1); 707-AP (707 alanine proline); ART-4 (adenocarcinoma antigen recognized by T4 cells); BAGE (B antigen; b-catenin/m, bcatenin/mutated); CAMEL (CTL-recognized antigen on melanoma); CAP1 (carcinoembryonic antigen peptide 1); CASP-8 (caspase-8); CDC27m (cell-division cycle 27 mutated); CDK4/m (cycline-dependent kinase 4 mutated); Cyp-B (cyclophilin B); DAM (differentiation antigen melanoma); EGP-2 (epithelial glycoprotein 2); EGP-40 (epithelial glycoprotein 40); Erbb 2, 3, 4 (erythroblastic leukemia viral oncogene homolog-2, -3, 4); FBP (folate binding protein); fAchR (Fetal acetylcholine receptor); G250 (glycoprotein 250); GAGE (G antigen); GnT-V (Nacetylglucosaminyltransferase V); HAGE (helicose antigen); ULA-A (human leukocyte antigen-A); HST2 (human signet ring tumor 2); KIAA0205; KDR (kinase insert domain receptor); LDLR/FUT (low density lipid receptor/GDP L-fucose: b-D-galactosidase 2-a-L fucosyltransferase); LICAM (LI cell adhesion molecule); MC1R (melanocortin 1 receptor); Myosin/m (myosin mutated); MUM-1, -2, -3 (melanoma ubiquitous mutated 1, 2, 3); NA88-A (NA cDNA clone of patient M88); KG2D (Natural killer group 2, member D) ligands; oncofeta antigen (h5T4); pi 90 minor bcr-abl (protein of 190KD bcr-abl); Pml/RARa (promyelocytic leukaemia/retinoic acid receptor a); PRAME (preferentially expressed antigen of melanoma); SAGE (sarcoma antigen); TEL/AML1 (translocation Ets-family leukemia/acute myeloid leukemia 1); TPI/m (triosephosphate isomerase mutated); CD70; and any combination thereof. 
     An anti-CLEC2D antibodies of the disclosure may be utilized to form a bispecific antibody, wherein the bispecific antibody specifically binds to CLEC2D and a second antigen, wherein the second antigen is an immune checkpoint inhibitor including but not limited to CTLA4, PPP2CA, PPP2CB, PTPN6, PTPN22, PDCD1, ICOS (CD278), PDL1, KIR, LAG3, HAVCR2, BTLA, CD160, TIGIT, CD96, CRTAM, LAIR1, SIGLEC7, SIGLEC9, CD244 (2B4), TNFRSF10B, TNFRSF10A, CASP8, CASP10, CASP3, CASP6, CASP7, FADD, FAS, TGFBRII, TGFRBRI, SMAD2, SMAD3, SMAD4, SMAD10, SKI, SKIL, TGIF1, IL10RA, IL10RB, HMOX2, IL6R, IL6ST, EIF2AK4, CSK, PAG1, SIT1, FOXP3, PRDM1, BATF, VISTA, GUCY1A2, GUCY1A3, GUCY1B2, GUCY1B3, MT1, MT2, CD40, OX40, CD137, GITR, CD27, SHP-1, TIM-3, CEACAM-1, CEACAM-3, or CEACAM-5. In some embodiments, an anti-CLEC2D antibodies of the disclosure, is a bispecific antibody, wherein the bispecific antibody specifically binds to CLEC2D and a second antigen, wherein the second antigen is an immune checkpoint gene and therapeutic target including but not limited to programmed cell death 1 (PD1), PD-L1, CLTA-4, T cell immunoglobulin and mucin 3 (TIM-3) and lymphocyte activating 3 (LAG-3). In some embodiments, an anti-CLEC2D antibodies of the disclosure, is a bispecific antibody, wherein the bispecific antibody specifically binds to CLEC2D and a second antigen, wherein the second antigen is associated with a cytokine or chemokine including but not limited to interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), granulocyte macrophage colony-stimulating factor (GM-CSF), IL-8, vascular endothelial growth factor (VEGF), stromal cell-derived factor-1, and interferon gamma-inducible protein-10 (IP-10), chemokines (CCL1, CCL2, CCL3, CCL4, CCL5, and CXCL8) or a combination thereof 
     In some embodiments, an anti-CLEC2D antibodies of the disclosure, is a bispecific antibody, wherein the bispecific antibody specifically binds to CLEC2D and a second antigen on the surface of a host cell. In some embodiments, an anti-CLEC2D antibodies of the disclosure, is a bispecific antibody, wherein the bispecific antibody comprises a first pair of variable light chain and variable heavy chain that specifically binds CLEC2D and a second pair of variable light chain and variable heavy chain that specifically binds to a second antigen on the surface of a host cell. In some embodiments, an anti-CLEC2D antibodies of the disclosure, is a bispecific antibody, wherein the bispecific antibody specifically binds to CLEC2D and a second antigen on the surface of a host cell, wherein the second antigen is an antigen associated with a cancer or tumor cell. 
     A bispecific antibody, as disclosed herein, may comprise constant regions representing specific isotypes e.g., human IgG1, IgG2, IgG3 and IgG4 or variants thereof, as described in this disclosure. A bispecific antibody, as disclosed herein, may comprise constant regions representing specific isotypes e.g., mouse IgG1, IgG2a, IgG2b or IgG3 or variants thereof, as described in this disclosure. A bispecific antibody, as disclosed herein, may having isotype backbones of IgG1, IgG1N297A and IgG4. A bispecific antibody, as disclosed herein, can be bispecific antibody formats using tri-functional antibody, chemically linked Fab, scFvs or disulfide bonded Fvs include tandem scFvs (often used as bispecific T cell engagers or ‘BiTEs’), tetravalent IgG-scFvs, diabodies, and many other formats. In some embodiments, a bispecific antibody, as disclosed herein, is produced as a diabody which are generated by combining sequences encoding two different scFvs into one construct in which heavy chains are expressed in a single polypeptide, and then joined with the corresponding light chains. 
     In some embodiments, an anti-CLEC2D antibodies of the disclosure, is a bispecific antibody, wherein the bispecific antibody specifically binds to CLEC2D and a second antigen on the surface of a host cell, wherein the second antigen is an antigen associated with a cancer, including but not limited to breast cancer, prostate cancer, endometrial cancer, bladder cancer, kidney cancer, esophageal cancer, squamous cell carcinoma, uveal melanoma, follicular lymphoma, renal cell carcinoma, cendcal cancer, ovarian cancer, lung cancer, colorectal cancer, brain cancer, pancreatic cancer, head and neck cancer, liver cancer, leukemia, lymphoma, Hodgkin&#39;s disease, multiple myeloma, melanoma, astrocytoma, stomach cancer, pulmonary adenocarcinoma, adenocarcinoma, acinic cell adenocarcinoma, adrenal cortical carcinomas, alveoli cell carcinoma, anaplastic carcinoma, basaloid carcinoma, basal cell carcinoma, bronchiolar carcinoma, bronchogenic carcinoma, renaladinol carcinoma, embryonal carcinoma, anometroid carcinoma, fibrolamolar liver cell carcinoma, follicular carcinomas, giant cell carcinomas, hepatocellular carcinoma, intraepidermal carcinoma, intraepithelial carcinoma, leptomanigio carcinoma, medullary carcinoma, melanotic carcinoma, menigual carcinoma, mesometonephric carcinoma, oat cell carcinoma, squamal cell carcinoma, sweat gland carcinoma, transitional cell carcinoma, tubular cell carcinoma, ameloblastic sarcoma, angiolithic sarcoma, botryoid sarcoma, endometrial stroma sarcoma, ewing sarcoma, fascicular sarcoma, giant cell sarcoma, granulositic sarcoma, immunoblastic sarcoma, juxaccordial osteogenic sarcoma, coppices sarcoma, leukocytic sarcoma (leukemia), lymphatic sarcoma (lympho sarcoma), medullary sarcoma, myeloid sarcoma (granulocitic sarcoma), austiogenci sarcoma, periosteal sarcoma, reticulum cell sarcoma (histiocytic lymphoma), round cell sarcoma, spindle cell sarcoma, synovial sarcoma, telangiectatic audiogenic sarcoma, Burkitt&#39;s lymphoma, NPDL, NML, NH and diffuse lymphomas. 
     In some embodiments, an anti-CLEC2D antibodies of the disclosure, is a bispecific antibody, wherein the bispecific antibody specifically binds to CLEC2D and a second antigen on the surface of a host cell, wherein the second antigen is an antigen associated with a cancer or tumor cell selected from the group consisting of breast cancer, prostate cancer, endometrial cancer, bladder cancer, kidney cancer, esophageal cancer, squamous cell carcinoma, uveal melanoma, follicular lymphoma, renal cell carcinoma, cendcal cancer, ovarian cancer, lung cancer, colorectal cancer, brain cancer, pancreatic cancer, head and neck cancer, liver cancer, leukemia, lymphoma, Hodgkin&#39;s disease, multiple myeloma, melanoma, astrocytoma, stomach cancer, and pulmonary adenocarcinoma. In some embodiments, an anti-CLEC2D antibodies of the disclosure, is a bispecific antibody, wherein the bispecific antibody specifically binds to CLEC2D and a second antigen on the surface of a host cell, wherein the second antigen is a tumor antigen selected from the group consisting of: B cell maturation antigen (BCMA); PSA (prostate-specific antigen); prostatespecific membrane antigen (PSMA); PSCA (Prostate stem cell antigen); Tyrosine-protein kinase transmembrane receptor ROR1; fibroblast activation protein (FAP); Tumor-associated glycoprotein 72 (TAG72); Carcinoembryonic antigen (CEA); Epithelial cell adhesion molecule (EPCAM); Mesothelin; Human Epidermal growth factor Receptor 2 (ERBB2 (Her2/neu)); Prostate; Prostatic acid phosphatase (PAP); elongation factor 2 mutant (ELF2M); Insulin-like growth factor 1 receptor (IGF-1R); gp100; BCR-ABL (breakpoint cluster region-Abelson); tyrosinase; New York esophageal squamous cell carcinoma 1 (NY-ESO-1); k-light chain, LAGE (L antigen); MAGE (melanoma antigen); Melanoma-associated antigen 1 (MAGE-A1); MAGE A3; MAGE A6; legumain; Human papillomavirus (HPV) E6; HPVE7; prostein; survivin; PCTA1 (Galectin 8); Melan-A/MART-1; Ras mutant; TRP-1 (tyrosinase related protein 1, or gp75); Tyrosinase-related Protein 2 (TRP2); TRP-2/INT2 (TRP-2/intron 2); RAGE (renal antigen); receptor for advanced glycation end products 1 (RAGED; Renal ubiquitous 1, 2 (RU1, RU2); intestinal carboxyl esterase (iCE); Heat shock protein 70-2 (HSP70-2) mutant; thyroid stimulating hormone receptor (TSHR); CD123; CD171; CD19; CD20; CD22; CD26; CD30; CD33; CD44v7/8 (cluster of differentiation 44, exons 7/8); CD53; CD92; CD100; CD148; CD150; CD200; CD261; CD262; CD362; CS-1 (CD2 subset 1, CRACC, SLAMF7, CD319, and 19A24); C-type lectin-like molecule-1 (CLL-1); ganglioside GD3 (aNeu5Ac(2-8)aNeu5Ac(2-3)bDGalp(1-4)bDG1cp(11)Cer); Tn antigen (Tn Ag); Fms-Like Tyrosine Kinase 3 (FLT3); CD38; CD138; CD44v6; B7H3 (CD276); KIT (CD1 17); Interleukin-13 receptor subunit alpha-2 (IL-13Ra2); Interleukin 11 receptor alpha (IL-11Ra); prostate stem cell antigen (PSCA); Protease Serine 2 1 (PRSS21); vascular endothelial growth factor receptor 2 (VEGFR2); Lewis(Y) antigen; CD24; Platelet derived growth factor receptor beta (PDGFR-beta); stage-specific embryonic antigen-4 (SSEA-4); Mucin 1, cell surface associated (MUC1); mucin 16 (MUC1 6); epidermal growth factor receptor (EGFR); epidermal growth factor receptor variant III (EGFRvIII); neural cell adhesion molecule (NCAM); carbonic anhydrase IX (CAIX); Proteasome (Prosome, Macropain) Subunit, Beta Type, 9 (LMP2); ephrin type-A receptor 2 (EphA2); Ephrin B2; Fucosyl GM1; sialyl Lewis adhesion molecule (sLe); ganglioside GM3 (aNeu5Ac(2-3)bDGalp(1-4)bDG1cp(1-1)Cer); TGS5; high molecular weight-melanoma-associated antigen (HMWMAA); o-acetyl-GD2 ganglioside (OAcGD2); Folate receptor alpha; Folate receptor beta; tumor endothelial marker 1 (TEM1/CD248); tumor endothelial marker 7-related (TEM7R); claudin 6 (CLDN6); G protein coupled receptor class C group 5, member D (GPRCSD); chromosome X open reading frame 6 1 (CXORF61); CD97; CD179a; anaplastic lymphoma kinase (ALK); Poly sialic acid; placenta specific1 (PLAC1); hexasaccharide portion of globoH glycoceramide (GloboH); mammary gland differentiation antigen (NY-BR-1); uroplakin 2 (UPK2); Hepatitis A virus cellular receptor 1 (HAVCR1); adrenoceptor beta 3 (ADRB3); pannexin 3 (PANX3); G protein-coupled receptor 20 (GPR20); lymphocyte antigen 6 complex, locus K 9 (LY6K); Olfactory receptor 51E2 (OR51E2); TCR Gamma Alternate Reading Frame Protein (TARP); Wilms tumor protein (WT1); ETS translocation-variant gene 6, located on chromosome 12p (ETV6-AML); sperm protein 17 (SPA17); X Antigen Family, Member 1A (XAGE1); angiopoietin-binding cell surface receptor 2 (Tie 2); CT (cancer/testis (antigen)); melanoma cancer testis antigen-1 (MAD-CT-1); melanoma cancer testis antigen-2 (MAD-CT-2); Fos-related antigen 1; p53; p53 mutant; human Telomerase reverse transcriptase (hTERT); sarcoma translocation breakpoints; melanoma inhibitor of apoptosis (ML-IAP); ERG (transmembrane protease, serine 2 (TMPRSS2) ETS fusion gene); NAcetyl glucosaminyl-transferase V (NA17); paired box protein Pax-3 (PAX3); Androgen receptor; Cyclin B1; Cyclin Dl; v-myc avian myelocytomatosis viral oncogene neuroblastoma derived homolog (MYCN); Ras Homolog Family Member C (RhoC); Cytochrome P450 1B1 (CYP1B1); CCCTC-Binding Factor (Zinc Finger Protein)-Like (BORIS); Squamous Cell Carcinoma Antigen Recognized By T Cells-1 or 3 (SART1, SART3); Paired box protein Pax-5 (PAX5); proacrosin binding protein sp32 (OY-TES1); lymphocyte-specific protein tyrosine kinase (LCK); A kinase anchor protein 4 (AKAP-4); synovial sarcoma, X breakpoint-1, -2, -3 or -4 (SSX1, SSX2, SSX3, SSX4); CD79a; CD79b; CD72; Leukocyte-associated immunoglobulin-like receptor 1 (LAIR1); Fc fragment of IgA receptor (FCAR); Leukocyte immunoglobulin-like receptor subfamily A member 2 (LILRA2); CD300 molecule-like family member f (CD300LF); C-type lectin domain family 12 member A (CLEC12A); bone marrow stromal cell antigen 2 (BST2); EGF-like module containing mucin-like hormone receptor-like 2 (EMR2); lymphocyte antigen 75 (LY75); Glypican-3 (GPC3); Fc receptor-like 5 (FCRL5); mouse double minute 2 homolog (MDM2); livin; alphafetoprotein (AFP); transmembrane activator and CAML Interactor (TACI); B-cell activating factor receptor (BAFF-R); V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS); immunoglobulin lambda-like polypeptide 1 (IGLL1); 707-AP (707 alanine proline); ART-4 (adenocarcinoma antigen recognized by T4 cells); BAGE (B antigen; b-catenin/m, bcatenin/mutated); CAMEL (CTL-recognized antigen on melanoma); CAP1 (carcinoembryonic antigen peptide 1); CASP-8 (caspase-8); CDC27m (cell-division cycle 27 mutated); CDK4/m (cycline-dependent kinase 4 mutated); Cyp-B (cyclophilin B); DAM (differentiation antigen melanoma); EGP-2 (epithelial glycoprotein 2); EGP-40 (epithelial glycoprotein 40); Erbb 2, 3, 4 (erythroblastic leukemia viral oncogene homolog-2, -3, 4); FBP (folate binding protein); fAchR (Fetal acetylcholine receptor); G250 (glycoprotein 250); GAGE (G antigen); GnT-V (Nacetylglucosaminyltransferase V); HAGE (helicose antigen); ULA-A (human leukocyte antigen-A); HST2 (human signet ring tumor 2); KIAA0205; KDR (kinase insert domain receptor); LDLR/FUT (low density lipid receptor/GDP L-fucose: b-D-galactosidase 2-a-L fucosyltransferase); LICAM (LI cell adhesion molecule); MC1R (melanocortin 1 receptor); Myosin/m (myosin mutated); MUM-1, -2, -3 (melanoma ubiquitous mutated 1, 2, 3); NA88-A (NA cDNA clone of patient M88); KG2D (Natural killer group 2, member D) ligands; oncofeta antigen (h5T4); pi 90 minor bcr-abl (protein of 190KD bcr-abl); Pml/RARa (promyelocytic leukaemia/retinoic acid receptor a); PRAME (preferentially expressed antigen of melanoma); SAGE (sarcoma antigen); TEL/AML1 (translocation Ets-family leukemia/acute myeloid leukemia 1); TPI/m (triosephosphate isomerase mutated); CD70; or a combination thereof. 
     In some embodiments, an anti-CLEC2D antibodies of the disclosure, is a bispecific antibody, wherein the bispecific antibody specifically binds to CLEC2D and a second antigen, wherein the second antigen is an antigen associated with an infectious agent or pathogen. In some embodiments, an anti-CLEC2D antibodies of the disclosure, is a bispecific antibody, wherein the bispecific antibody specifically binds to CLEC2D and a second antigen, wherein the second antigen is an antigen associated with a microorganism. In some embodiments, an anti-CLEC2D antibodies of the disclosure, is a bispecific antibody, wherein the bispecific antibody specifically binds to CLEC2D and a second antigen, wherein the second antigen is an antigen associated with a microorganisms including but not limited to bacteria, fungi, protozoa, parasites, and viruses. In some embodiments, an anti-CLEC2D antibodies of the disclosure, is a bispecific antibody, wherein the bispecific antibody specifically binds to CLEC2D and a second antigen, wherein the second antigen is an antigen associated with a microorganisms including but not limited to a pathogenic bacteria, fungi, protozoa, parasites, and viruses. In some embodiments, an anti-CLEC2D antibodies of the disclosure, is a bispecific antibody, wherein the bispecific antibody specifically binds to CLEC2D and a second antigen, wherein the second antigen is an antigen associated with a microorganisms including but not limited to an intracellular bacteria. In some embodiments, an anti-CLEC2D antibodies of the disclosure, is a bispecific antibody, wherein the bispecific antibody specifically binds to CLEC2D and a second antigen, wherein the second antigen is an antigen that is specifically expressed on a host cell infected with a microorganisms including but not limited to a pathogenic bacteria, fungi, protozoa, parasites, and viruses. 
     In some embodiments, an anti-CLEC2D antibodies of the disclosure, is a bispecific antibody, wherein the bispecific antibody specifically binds to CLEC2D and a second antigen, wherein the second antigen is an antigen associated with inflammatory or autoimmune disorders including but not limited to seronegative spondyloarthropathies, connective tissue diseases, inflammatory bowel diseases, arthritis, inflammatory skin conditions, inflammatory lung diseases, inflammatory renal disease, systemic vasculitis, macrophage activation diseases, polymyalgia rheumatica, primary biliary sclerosis, sclerosing cholangitis, autoimmune hepatitis, Type 1 Diabetes Mellitus, Hashimoto&#39;s thyroiditis, Graves&#39; disease, multiple sclerosis (MS), Guillain-Barre syndrome, Addison&#39;s disease, Raynaud&#39;s phenomenon and Goodpasture&#39;s syndrome. 
     In some embodiments, an anti-CLEC2D antibodies of the disclosure, is a bispecific antibody, wherein the bispecific antibody specifically binds to CLEC2D and a second antigen, wherein the second antigen is an antigen associated with connective tissue diseases such as juvenile rheumatoid arthritis, rheumatoid arthritis, systemic lupus erythematosus (SLE) and lupus nephritis, scleroderma, Sjogren&#39;s syndrome, mixed connective tissue disease and polymyositis, dermatomyositis. 
     In some embodiments, an anti-CLEC2D antibodies of the disclosure, is a bispecific antibody, wherein the bispecific antibody specifically binds to CLEC2D and a second antigen, wherein the second antigen is an antigen associated with Whipples disease and arthritis associated with granulomatous ileocolitis, inflammatory skin conditions such as autoimmune bullous pemphigoid, autoimmune pemphigus vulgaris, eczema and dermatitis, inflammatory lung diseases such as alveolitis, pulmonary fibrosis, sarcoidoisis, asthma, bronchitis and bronchiolitis obliterans, inflammatory renal diseases such as glomerulonethritis, renal allograft rejection and renal tubular inflammation, atherosclerosis, systemic vasculitis such as temporal arteritis/giant cell arteritis, takayasu arteritis, polyarteritis nodosa, Kawasaki disease, Wegener&#39;s granulomatosis, churg strauss syndrome, microscopic polyangiitis, necrotising glomerulonephritis, henoch schonlein purpura, essential cryoglobulinaemic vasculitis, other small vessel vasculitis and Behcets disease, macrophage activation diseases such as macrophage activation syndrome (MAS), adult onset stills disease, haemophagocytic syndrome, polymyalgia rheumatica, primary biliary sclerosis, sclerosing cholangitis, autoimmune hepatitis, Type 1 Diabetes Mellitus, Hashimoto&#39;s thyroiditis, Graves&#39; disease, multiple sclerosis (MS), Guillain-Barre syndrome, Addison&#39;s disease, and/or Raynaud&#39;s phenomenon and Goodpasture&#39;s syndrome. 
     The bispecific antibodies of the invention are generated using any methods known in the art such as, by way of non-limiting example, the use of cross-linked fragments, quadromas, and/or any of a variety of recombinant formats such as, by way of non-limiting examples, linked antibody fragments, forced heterodimers, and or recombinant formats based on single domains. Examples of Bispecific formats include but are not limited to bispecific IgG based on Fab arm exchange (Gramer et al., 2013 MAbs. 5(6)); the CrossMab format (Klein C et al., 2012 MAbs 4(6)); multiple formats based on forced heterodimerization approaches such as SEED technology (Davis J H et al., 2010 Protein Eng Des Sel. 23(4):195-202), electrostatic steering (Gunasekaran K et al., J Biol Chem. 2010 285(25):19637-46.) or knob-into-hole (Ridgway J B et al., Protein Eng. 1996 9(7):617-21.) or other sets of mutations preventing homodimer formation (Von Kreudenstein T S et al., 2013 MAbs. 5(5):646-54.); fragment based bispecific formats such as tandem scFv (such asBiTEs) (Wolf E et al., 2005 Drug Discov. Today 10(18):1237-44.); bispecific tetravalent antibodies (Portner L M et al., 2012 Cancer Immunol Immunother. 61(10):1869-75.); dual affinity retargeting molecules (Moore P A et al., 2011 Blood. 117(17):4542-51), diabodies (Kontermann R E et al., Nat Biotechnol. 1997 15(7):629-31). 
     In some embodiments, the anti-CLEC2D antibodies and compositions and the additional therapeutic agent(s) act additively to treat a sign or a symptom of a disease. 
     In some embodiments, the anti-CLEC2D antibodies and compositions and the additional therapeutic agent(s) act synergistically to treat a sign or a symptom of a disease. 
     In some embodiments, the combination of anti-CLEC2D antibodies and compositions with an additional therapeutic agents leads to superior efficacy in the treatment of the disease or disorder, including increased reduction of one or more symptoms of the disease or disorder, the reduction in one or more side effects of the treatment, or a reduction in the therapeutically effective dose of the anti-CLEC2D antibodies or compositions or the additional therapeutic agent. 
     The antibodies or antigen-binding fragments thereof can be conjugated to another therapeutic modality. The conjugation may bring the antibodies or antigen-binding fragments thereof of the present disclosure into close proximity to the target, such as a target cell, improve the target specificity, increase the overall binding affinity of the conjugate to the target, and/or enhance the cytotoxicity of the NK cells towards the target, which increase the therapeutic efficacy and/or specificity of the antibodies or antigen-binding fragments thereof of the present disclosure. The another therapeutic modality can be any of the additional therapeutic agents described herein. Methods of making antibody conjugates are known in the art, for example, through protein-coupling agents such as N-succinimidyl-3-(2-pyridyldithiol) propionate (SPDP), iminothiolane (IT), bifunctional derivatives of imidoesters (such as dimethyl adipimidate HCL), active esters (such as disuccinimidyl suberate), aldehydes (such as glutareldehyde), bis-azido compounds (such as bis (p-azidobenzoyl) hexanediamine), bis-diazonium derivatives (such as bis-(p-diazoniumbenzoyl)-ethylenediamine), diisocyanates (such as tolyene 2,6-diisocyanate), and bis-active fluorine compounds (such as 1,5-difluoro-2,4-dinitrobenzene). Coupling may be accomplished by any chemical reaction that will bind the two molecules so long as the antibody and the other moiety retain their respective activities. This linkage can include many chemical mechanisms, for instance covalent binding, affinity binding, intercalation, coordinate binding and complexation. The preferred binding is, however, covalent binding. Covalent binding can be achieved either by direct condensation of existing side chains or by the incorporation of external bridging molecules. Many bivalent or polyvalent linking agents are useful in coupling protein molecules, such as the antibodies of the present invention, to other molecules. For example, representative coupling agents can include organic compounds such as thioesters, carbodiimides, succinimide esters, diisocyanates, glutaraldehyde, diazobenzenes and hexamethylene diamines. This listing is not intended to be exhaustive of the various classes of coupling agents known in the art but, rather, is exemplary of the more common coupling agents. (See Killen and Lindstrom, Jour. Immun. 133:1335-2549 (1984); Jansen et al., Immunological Reviews 62:185-216 (1982); and Vitetta et al., Science 238:1098 (1987). 
     The antibodies or antigen-binding fragments thereof of the present disclosure can also be used to make a bi-specific antibody. For example, the antibodies or antigen-binding fragments thereof of the present disclosure can be combined with the additional antibodies or antigen-binding fragments thereof described herein to form a bi-specific antibody. Methods of making bispecific antibodies are known in the art. 
     Dosage regimens are adjusted to provide the optimum desired response, e.g., therapeutic response or minimal adverse effects. For example, for administration of an anti-CLEC2D antibody, the dosage can range from about 0.0001 to about 1000 mg/kg. For example, dosages can be at least 0.1, at least 0.3, at least 1, at least 3, at least 5, at least 10, at least 15, at least 20 or at least 25 mg/kg body weight. The dosing schedule is typically designed to achieve exposures that result in sustained receptor occupancy based on typical pharmacokinetic properties of an antibody. An exemplary treatment regime entails administration once per week, once every two weeks, once every three weeks, once every four weeks, once a month, once every 3 months or once every three to 6 months. The dosage and scheduling may change during a course of treatment. For example, dosing schedule may comprise administering the antibody: (i) every two weeks in 6-week cycles; (ii) every four weeks for six dosages, then every three months; (iii) every three weeks; (iv) with an initial high dose followed by a periodic lower maintenance dose. Intervals between single dosages can be, for example, weekly, every 2 weeks, every 3 weeks, monthly, every three months or yearly. Intervals can also be irregular as indicated by measuring blood levels of antibody to the target antigen in the patient. In some methods, dosage is adjusted to achieve a desired plasma a concentration of the antibody. 
     In some embodiments, the Ab can be administered as a sustained release formulation, in which case less frequent administration is required. Dosage and frequency vary depending on the half-life of the antibody in the patient. In general, human antibodies show the longest half-life, followed by humanized antibodies, chimeric antibodies, and nonhuman antibodies. The dosage and frequency of administration can vary depending on whether the treatment is prophylactic or therapeutic. In prophylactic applications, a relatively low dosage is typically administered at relatively infrequent intervals over a long period of time. Some patients continue to receive treatment for the rest of their lives. In therapeutic applications, a relatively high dosage at relatively short intervals is sometimes required until progression of the disease is reduced or terminated, and preferably until the patient shows partial or complete amelioration of symptoms of disease. Thereafter, the patient can be administered a prophylactic regime. 
     Actual dosage levels of the active ingredients in the pharmaceutical compositions of the present disclosure may be varied so as to obtain an amount of the active ingredient which is effective to achieve the desired therapeutic response for a particular patient, composition, and mode of administration, without being unduly toxic to the patient. The selected dosage level will depend upon a variety of pharmacokinetic factors including the activity of the particular compositions of the present disclosure employed, the route of administration, the time of administration, the rate of excretion of the particular compound being employed, the duration of the treatment, other drugs, compounds and/or materials used in combination with the particular compositions employed, the age, sex, weight, condition, general health and prior medical history of the patient being treated, and like factors well known in the medical arts. A composition of the present disclosure can be administered via one or more routes of administration using one or more of a variety of methods well known in the art. As will be appreciated by the skilled artisan, the route and/or mode of administration will vary depending upon the desired results. 
     Diagnosis and Prognosis 
     The disclosure provides a method of treating a disease in a subject in need thereof, comprising: determining the level of CLEC2D protein in the subject; and administering a therapeutically effective amount of a CLEC2D antibody to the subject. In one embodiment, the level of CLEC2D protein is determined by measuring the level of CLEC2D expression in a cell from the subject. In one embodiment, the cell is a cancer cell (e.g., a cell from a cancer described herein). 
     The disclosure provides a method of treating a disease in a subject in need thereof, comprising: obtaining a sample from the subject; determining the level of CLEC2D protein in the sample; if the level of CLEC2D protein in the sample is higher than the level of CLEC2D protein in a control sample, administering a therapeutically effective amount of a CLEC2D antibody to the subject. In one embodiment, the sample is a cell from the subject. In one embodiment, the cell is from a diseased tissue or organ. In one embodiment, the cell is a cancer cell (e.g., a cell from a cancer described herein). In one embodiment, the control sample is from a non-diseased tissue or organ of the subject. In one embodiment, the control sample is from a subject which does not have the disease. 
     The disclosure provides a method of treating a disease in a subject in need thereof, comprising: obtaining a first sample from the subject; determining a first level of CLEC2D protein in the first sample; administering a therapeutically effective amount of a CLEC2D antibody to the subject; obtaining a second sample from the subject; determining a second level of CLEC2D protein in the second sample; comparing the second level with the first level; if the first level is greater than the second level, continuing administration of a therapeutically effective amount of the CLEC2D antibody to the subject. In one embodiment, the sample is a cell from the subject. In one embodiment, the cell is from a diseased tissue or organ. In one embodiment, the cell is a cancer cell (e.g., a cell from a cancer described herein). In one embodiment, the control sample is from a non-diseased tissue or organ of the subject. In one embodiment, the control sample is from a subject which does not have the disease. 
     The disclosure provides a method of treating a disease in a subject in need thereof, comprising: obtaining a first sample from the subject; determining a first level of CLEC2D protein in the first sample; administering a first therapeutically effective amount of a CLEC2D antibody to the subject; obtaining a second sample from the subject; determining a second level of CLEC2D protein in the second sample; comparing the second level with the first level; if the first level is lower than the second level, administering a second therapeutically effective amount of the CLEC2D antibody to the subject, wherein the second therapeutically effective amount is greater than the first therapeutically effective amount. In one embodiment, the sample is a cell from the subject. In one embodiment, the cell is from a diseased tissue or organ. In one embodiment, the cell is a cancer cell (e.g., a cell from a cancer described herein). In one embodiment, the control sample is from a non-diseased tissue or organ of the subject. In one embodiment, the control sample is from a subject which does not have the disease. 
     The disclosure provides a method of treating a disease in a subject in need thereof, comprising: obtaining a first sample from the subject; determining a first level of CLEC2D protein in the first sample; administering a therapeutically effective amount of a CLEC2D antibody to the subject; obtaining a second sample from the subject; determining a second level of CLEC2D protein in the second sample; comparing the second level with the first level; if the first level is lower than the second level, terminating administration of the CLEC2D antibody to the subject. In one embodiment, the sample is a cell from the subject. In one embodiment, the cell is from a diseased tissue or organ. In one embodiment, the cell is a cancer cell (e.g., a cell from a cancer described herein). In one embodiment, the control sample is from a non-diseased tissue or organ of the subject. In one embodiment, the control sample is from a subject, which does not have the disease. 
     The isolated, novel antibody clones can be used to determine stage and aggressiveness of disease and to treat the disease appropriately. 
     The disclosure provides anti-CLEC2D antibodies and antibody fragments thereof, nucleic acids encoding the antibodies or antigen binding fragments thereof, or compositions comprising same, for use in the diagnosis and prognosis of diseases and disorders. 
     In some embodiments, isolated monoclonal antibodies reveal the differential expression of CLEC2D on various tumor cell surfaces, indicating that CLEC2D is a novel biomarker for the diagnosis of various disease conditions. Further CLEC2D antigen is significantly overexpressed on various tumors, indicating the usefulness of this target molecule as a novel molecular marker for disease diagnosis. Moreover, the expression level of CLEC2D significantly increases under the influence of various inducing agents. The differential expression of CLEC2D antigen on induced tumor cells is correlated with different stages of disease, disease progression, metastasis, and so on. Therefore CLEC2D has an enormous potential of prognostic biomarker. In some embodiments, an increase in CLEC2D protein expression, for example on a cancer cell in a subject, is associated with a poorer prognostic outcome than if CLEC2D protein expression is not elevated. 
     As detailed herein, isolated monoclonal antibodies are used to monitor CLEC2D surface expression on tumor cell lines. 
     Anti-CLEC2D antibodies can be used to diagnose and prognose diseases including, but not limited to breast cancer, prostate cancer, endometrial cancer, bladder cancer, kidney cancer, esophageal cancer, squamous cell carcinoma, uveal melanoma, follicular lymphoma, renal cell carcinoma, cendcal cancer, ovarian cancer, lung cancer, colorectal cancer, brain cancer, pancreatic cancer, head and neck cancer, liver cancer, leukemia, lymphoma, Hodgkin&#39;s disease, multiple myeloma, melanoma, astrocytoma, stomach cancer, pulmonary adenocarcinoma, adenocarcinoma, acinic cell adenocarcinoma, adrenal cortical carcinomas, alveoli cell carcinoma, anaplastic carcinoma, basaloid carcinoma, basal cell carcinoma, bronchiolar carcinoma, bronchogenic carcinoma, renaladinol carcinoma, embryonal carcinoma, anometroid carcinoma, fibrolamolar liver cell carcinoma, follicular carcinomas, giant cell carcinomas, hepatocellular carcinoma, intraepidermal carcinoma, intraepithelial carcinoma, leptomanigio carcinoma, medullary carcinoma, melanotic carcinoma, menigual carcinoma, mesometonephric carcinoma, oat cell carcinoma, squamal cell carcinoma, sweat gland carcinoma, transitional cell carcinoma, tubular cell carcinoma, ameloblastic sarcoma, angiolithic sarcoma, botryoid sarcoma, endometrial stroma sarcoma, ewing sarcoma, fascicular sarcoma, giant cell sarcoma, granulositic sarcoma, immunoblastic sarcoma, juxaccordial osteogenic sarcoma, coppices sarcoma, leukocytic sarcoma (leukemia), lymphatic sarcoma (lympho sarcoma), medullary sarcoma, myeloid sarcoma (granulocitic sarcoma), austiogenci sarcoma, periosteal sarcoma, reticulum cell sarcoma (histiocytic lymphoma), round cell sarcoma, spindle cell sarcoma, synovial sarcoma, telangiectatic audiogenic sarcoma, Burkitt&#39;s lymphoma, NPDL, NML, NH and diffuse lymphomas. 
     In spite of various treatment options currently available, multiple cancers, such as breast cancer, prostate cancer, endometrial cancer, bladder cancer, kidney cancer, esophageal cancer, squamous cell carcinoma, uveal melanoma, follicular lymphoma, renal cell carcinoma, cendcal cancer, ovarian cancer, lung cancer, colorectal cancer, brain cancer, pancreatic cancer, head and neck cancer, liver cancer, leukemia, lymphoma, Hodgkin&#39;s disease, multiple myeloma, melanoma, astrocytoma, stomach cancer, and pulmonary adenocarcinoma, still remain as leading causes of death in people world-wide and lack unique therapeutic prospects. Diagnosis of these diseases at an early stage is one of the most important factors that determine survival. The present disclosure describes identification of CLEC2D as a biomarker target for these diseases and others, having profound therapeutic implications. The rapid advancement in overall antibody identification methods against CLEC2D, described in present disclosure, have made it possible to validate CLEC2D as novel biomarker against various disease indications mentioned above. 
     The present disclosure provides anti-CLEC2D antibodies and fragments thereof, and compositions comprising the same, as for use in the identification of CLEC2D expression as a predictive biomarker to stratify patients who are likely to have better response on certain treatments. 
     The present disclosure provides anti-CLEC2D antibodies and fragments thereof, nucleic acids encoding the antibodies or antigen binding fragments thereof, or compositions comprising the same, as for use in the identification of CLEC2D expression as a predictive biomarker and to pave the way to explore therapies aimed at enhancing NK cells cytolytic activity in metastatic cancer patients. In some embodiments, expression of these CLEC2D receptors on immune cells in the tumor microenvironment is associated with good prognosis. The expression of specific molecules on specific immune cells, such as NK cells and T cells, is involved in maintenance of particular immune function. The present disclosure describes the prognostic role of CLEC2D expression as NK receptor ligands, including in prostate cancer, and the association of CLEC2D expression with different prostate cancer disease stages, molecular subtypes and clinic-pathological features. Blocking CLEC2D expression on tumor cells with an anti-CLEC2D antibody signals in an NK cell mediated cytotoxic immune context and harnesses the positive prognostic value of infiltrating T cells. The human anti-CLEC2D monoclonal antibodies of the disclosure expand the opportunity/scope of these antibodies not only as therapeutic, also, as prognostic and diagnostics in various cancer types either alone or in association with other ligands, cytokines or other cellular factors. 
     Pharmaceutical Formulations 
     The disclosure provides a pharmaceutical composition of any of the anti-CLEC2D antibodies or antibody fragments thereof of the disclosure. Each of the anti-CLEC2D antibodies of the present disclosure can be formulated into a composition suitable for administration to the subject. In exemplary aspects, each of the anti-CLEC2D antibodies can be formulated with one or more agents which enhance the chemico-physico features of the anti-CLEC2D antibody, e.g., via stabilizing the anti-CLEC2D antibody at certain temperatures, e.g., room temperature, increasing shelf life, reducing degradation, e.g., oxidation protease mediated degradation, increasing half-life of the anti-CLEC2D antibody, etc. In exemplary aspects of the present disclosure, the anti-CLEC2D antibody may be formulated into a composition additionally comprising a pharmaceutically acceptable carrier, diluents, or excipient. 
     “Pharmaceutical compostions” and “pharmaceutical formulations” are used interchangeably herein unless the context clearly suggests otherwise. 
     The pharmaceutical compositions can be solid, semi-solid, or liquid. Generally the pharmaceutical composition is adapted for a particular route of administration. For example, the pharmaceutical composition can be adapted for oral administration, rectal administration, buccal administration, topical administration, etc. Preferably, the pharmaceutical composition is adapted for intravenous administration. In some embodiments the pharmaceutical composition comprising antibodies or antibody fragments of the disclosure is suitable for intravenous injection or infusion. In some embodiments, the aqueous stable monoclonal antibody formulation will be administered by parenteral routes preferably via intramuscular injection, sub-cutaneous injection, i.v. injection or, most preferably, i.v. infusion. 
     As used herein, a “pharmaceutically acceptable carrier” includes any and all solvents, dispersion media, coatings, antibacterial and antifungal agents, isotonic and absorption delaying agents, and the like that are physiologically compatible. Preferably, the carrier is suitable for intravenous, intramuscular, subcutaneous, parenteral, spinal or epidermal administration (e.g., by injection or infusion). A pharmaceutical composition of this disclosure may include one or more pharmaceutically acceptable salts, anti-oxidant, aqueous and nonaqueous carriers; and/or adjuvants such as preservatives, wetting agents, emulsifying agents and dispersing agents. For example, a pharmaceutically acceptable carrier includes any of the standard pharmaceutical carriers, such as a phosphate buffered saline solution, water, emulsions such as an oil/water or water/oil emulsion, and various types of wetting agents. The term also encompasses any of the agents approved by a regulatory agency of the US Federal government or listed in the US Pharmacopeia for use in animals, including humans. 
     The pharmaceutical composition can comprise any pharmaceutically acceptable ingredients, including, for example, acidifying agents, additives, adsorbents, aerosol propellants, air displacement agents, alkalizing agents, anticaking agents, anticoagulants, antimicrobial preservatives, antioxidants, antiseptics, bases, binders, buffering agents, chelating agents, coating agents, coloring agents, desiccants, detergents, diluents, disinfectants, disintegrants, dispersing agents, dissolution enhancing agents, dyes, emollients, emulsifying agents, emulsion stabilizers, fillers, film forming agents, flavor enhancers, flavoring agents, flow enhancers, gelling agents, granulating agents, humectants, lubricants, mucoadhesives, ointment bases, ointments, oleaginous vehicles, organic bases, pastille bases, pigments, plasticizers, polishing agents, preservatives, sequestering agents, skin penetrants, solubilizing agents, solvents, stabilizing agents, suppository bases, surface active agents, surfactants, suspending agents, sweetening agents, therapeutic agents, thickening agents, tonicity agents, toxicity agents, viscosity-increasing agents, water-absorbing agents, watermiscible cosolvents, water softeners, or wetting agents. Other pha.rmaceutically acceptable excipients known in the art include diluents, carders, fillers, binders, lubricants, disintegrants, glidants, colorants, pigments, taste masking agents, sweeteners, plasticizers, and any acceptable auxiliary substances such as absorption enhancers, penetration enhancers, surfactants; co-surfactants, preservatives, anti-oxidants and specialized oils. Specific; to the field of biopharmaceutical proteins are excipients intended to stabilize proteins and cryo-protectants to provide protection during freeze-drying. Suitable excipient(s) are selected based in part on the dosage form, the intended mode of administration, the intended release rate, and manufacturing reliability. Non-limiting examples of commonly used excipients include polymers, waxes, calcium phosphates, sugars (e.g., trehalose, sucrose, or mannitol), buffers (such as phosphate, acetate, citrate, histidine, or glycine based buffers at pH between 5 and 7.5), salts (e.g., NaCl or NaEDTA), polysorbate 20, polysorbate 80; human albumin, dextran, and benzyl alcohol. See, e.g., the Handbook of Pharmaceutical Excipients, Third Edition, A. H. Kibbe (Pharmaceutical Press, London, U K, 2000), which is incorporated by reference in its entirety. Remington&#39;s Pharmaceutical Sciences, Sixteenth Edition, E.W. Martin (Mack Publishing Co., Easton, Pa., 1980), which is incorporated by reference in its entirety. 
     In exemplary aspects, the pharmaceutical composition comprises formulation materials that are nontoxic to recipients at the dosages and concentrations employed. In specific embodiments, pharmaceutical compositions comprising an active agent and one or more pharmaceutically acceptable salts; polyols; surfactants; osmotic balancing agents; tonicity agents; anti-oxidants; antibiotics; antimycotics; bulking agents; lyoprotectants; anti-foaming agents; chelating agents; preservatives; colorants; analgesics; or additional pharmaceutical agents. 
     In exemplary aspects, the pharmaceutical composition comprises one or more polyols and/or one or more surfactants, optionally, in addition to one or more excipients, including but not limited to, pharmaceutically acceptable salts; osmotic balancing agents (tonicity agents); anti-oxidants; antibiotics; antimycotics; bulking agents; lyoprotectants; antifoaming agents; chelating agents; preservatives; colorants; and analgesics. 
     In certain embodiments, the pharmaceutical composition can contain formulation materials for modifying, maintaining or preserving, for example, the pH, osmolarity, viscosity, clarity, color, isotonicity, odor, sterility, stability, rate of dissolution or release, adsorption or penetration of the composition. In such embodiments, suitable formulation materials include, but are not limited to, amino acids (such as glycine, glutamine, asparagine, arginine or lysine); antimicrobials; antioxidants (such as ascorbic acid, sodium sulfite or sodium hydrogen-sulfite); buffers (such as borate, bicarbonate, Tris-HCl, citrates, phosphates or other organic acids); bulking agents (such as mannitol or glycine); chelating agents (such as ethylenediamine tetraacetic acid (EDTA)); complexing agents (such as caffeine, polyvinylpyrrolidone, beta-cyclodextrin or hydroxypropyl-beta-cyclodextrin); fillers; monosaccharides; disaccharides; and other carbohydrates (such as glucose, mannose or dextrins); proteins (such as serum albumin, gelatin or immunoglobulins); coloring, flavoring and diluting agents; emulsifying agents; hydrophilic polymers (such as polyvinylpyrrolidone); low molecular weight polypeptides; salt-forming counterions (such as sodium); preservatives (such as benzalkonium chloride, benzoic acid, salicylic acid, thimerosal, phenethyl alcohol, methylparaben, propylparaben, chlorhexidine, sorbic acid or hydrogen peroxide); solvents (such as glycerin, propylene glycol or polyethylene glycol); sugar alcohols (such as mannitol or sorbitol); suspending agents; surfactants or wetting agents (such as pluronics, PEG, sorbitan esters, polysorbates such as polysorbate 20, polysorbate, triton, tromethamine, lecithin, cholesterol, tyloxapal); stability enhancing agents (such as sucrose or sorbitol); tonicity enhancing agents (such as alkali metal halides, preferably sodium or potassium chloride, mannitol sorbitol); delivery vehicles; diluents; excipients and/or pharmaceutical adjuvants. See, REMINGTON&#39;S PHARMACEUTICAL CAR-TSCIENCES, 18″ Edition, (A. R. Genrmo, ed.), 1990, Mack Publishing Company. 
     The pharmaceutical compositions can be formulated to achieve a physiologically compatible pH. In some embodiments, the pH of the pharmaceutical composition can be for example between about 4 or about 5 and about 8.0, between about 4.5 and about 7.5, or between about 5.0 to about 7.5. In exemplary embodiments, the pH of the pharmaceutical composition is between 5.5 and 7.5. 
     Pharmaceutical compositions for administering the anti-CLEC2D antibodies via parenteral administration are typically liquid. Water is commonly used as a main excipient, although other pharmaceutically-acceptable liquids such as ethanol, glycerol, ethyl oleate, Myglyol benzyol oleate, castor oil, MCT, benzyl alcohol isopropyl myristate can be used alone or in combination with water or each other. Aqueous compositions that contain no other excipients are also contemplated, and can be prepared from lyophilized, amorphous, or crystalline compounds. Often the injectable composition, which can be for subcutaneous, IM, or IV injection, contains isotonizing agents. An injectable solution or suspension is typically sterile, as are all liquid pharmaceutical dosage forms. 
     Pharmaceutical compositions for administering anti-CLEC2D antibodies via topical administration include powders, creams, ointments, gels, lotions, solutions and suspensions (including mouth washes). The excipient earlier is often aqueous, oil, or polymer based, each optionally in the form of an emulsion or microemulsion. The term “topical administration” includes, for example, optical administration (e.g., via a cream/ointment) and administration to the skin (e.g., at an inflamed joint). 
     Pharmaceutical compositions for administering anti-CLEC2D antibodies via oral administration include solid oral dosage forms such as tablets, capsules, enteric coated forms thereof, lozenges, and films, as well as liquid dosage forms including solutions, suspensions, liquid filled capsules, and mouth washes. Tablets can be soluble tablets, dispersible tablets, effervescent tablets, chewable tablets, lyophilized tablets, coated tablets (e.g., sugar-coated or enteric-coated), and modified release tablets. Capsules include hard gelatin capsules that can be filled with powder, pellets, granules, small tablets, or mini-tablets, or solutions or emulsions or combinations and can be coated for enteric or modified release. Soft capsules are also contemplated and are more typically filled with liquids, gels or dispersions; but are not limited thereto. Granules can be effervescent granules, coated granules (e.g., sugar-coated or enteric-coated); and modified release granules. Although the anti-CLEC2D antibodies of the present disclosure can be administered orally, it should be understood that such administration may be considered to be a topical administration to the (ii tract. Likewise, a suppository or rectal injection may also be used to topically to the intestines. The use of an oral dosage form to treat gastrointestinal disease(s) using the anti-CLEC2D antibodies of the present disclosure is an aspect of the present disclosure. 
     An overview of dosage forms can be found in Ansel&#39;s Pharmaceutical Dosage forms and Drug Delivery Systems. 9 th  ed. L. V. Allan, N. G. Popovitch, H. C. Ansel; 2010 Lippincott, ISBN 978-0781779340; Formularium der Nederlandse Apothekers 2004 WINAp ISBN 90-70605-75-9; Recepteerkunde, G. K. Bolhuis, Bouwman-Boer, F. Kadir en J. Zuiderma, 2005 WINAp ISBN 90-70605-65-1; and Apothekenrezeptur und-defektur. Deutscher Apotheker Verlag Stuttgart 1986 ISBN 3-7692-1092-1. See also U.S. Pat. No. 7,147,854 for a description of topical preparations for delivering IL-S antibodies to treat skin inflammatory disease such as psoriasis. 
     The pharmaceutical composition generally contains about 0.01 to 1000 mg of the antibody per dose, depending in part upon the dosage form employed. The dose can be, for example, fixed or variable (e.g., based on body weight). 
     Development of a stable formulation is vital to successful clinical manufacturing of pharmaceutical compositions comprising the antibodies and antigen binding fragments of the disclosure. 
     In some embodiments, a stable formulation is prepared by screening various buffers, stabilizers at different pH with the help of additives and the final stable formulation should contain the physical, chemical stability and biological activity upon storage. The role of excipients in the stable formulation is to prevent and/or reduce the rate of degradation in order to provide an acceptable shelf life. 
     The current disclosure provides, in some embodiments, a stable liquid and/or lyophilized formulation of anti-CLEC2D monoclonal antibodies. In some embodiments, a formulation buffer contemplated for use in the present disclosure has a pH in the range from 4.0 to 8.0; preferably in the pH range from 4.5 to 7.5; most preferably in the pH range between 5.0 and 6.5. 
     In some embodiments, the present disclosure comprises buffering agents that can be any of the following and combinations thereof, sodium citrate, citric acid; sodium phosphate mono basic, sodium phosphate dibasic; potassium phosphate mono basic, potassium phosphate dibasic; acetic acid, sodium acetate; histidine, histidine HCl; succinic acid, sodium succinate; tartaric acid, sodium tartrate; maleic acid, maleate; succinate 2-(N-morpholino) ethane sulfonic acid (MES) and hydrochloric acid and sodium hydroxide to adjust the pH to desired range. 
     In some embodiments, the composition comprises other buffers such as Tris buffer, (3-(N-morpholino)propanesulfonic acid) (MOPS), MOPS-SDS (MEPS), N-cyclohexyl-2-hydroxyl-3-aminopropanesulfonic acid (CAPSO), piperazine-N,N′-bis(2-ethanesulfonic acid) (PIPES) etc. some embodiments, the formulation comprises polyols, which are sugar alcohols. In some embodiments, the stabilizers in the formulation comprise any one of the following alone or in combination: a-trehalose, sucrose, mannitol, sorbitol. In other embodiments, the formulation comprises a second stabilizer that are any one of the following: methionine, lysine, arginine, glycine, glutamate etc. 
     In some embodiments, the present antibody formulations comprise hydrophobic salts namely sodium camphor sulphate, tri methyl ammonium iodide. In another embodiment, the present disclosure of anti-CLEC2D monoclonal antibody formulation comprises surfactants, as well. In some embodiments, any one of following surfactants are included in the formulations, as exemplified by Polysorbate 20, Polysorbate 40, Polysorbate 80, and Poloxamer 188. In some embodiments, the composition comprising an anti-CLEC2D monoclonal antibody comprises anti-oxidants, for example methionine and/or glutathione. In some embodiments, the composition comprises hydrochloric acid and sodium hydroxide to adjust the pH of formulation buffer. 
     In some embodiments, the present disclosure comprises other stabilizing and complexing agents such as disodium edetate (Na(2)EDTA) and diethylene triaminepentaacetic acid (DTPA). In some embodiments, all the excipients of the stable formulation are dissolved in water for injection (WFI). 
     In one embodiment, the final aqueous stable formulation is filtered suitably to remove particulate matter. In some embodiments, filtration is done through either polyethersulfone (PES) filters, Polyvinylidene Fluoride (PVDF) filters or regenerated cellulose (RC) filters, suitably filters sized at either 0.22 and/or 0.45 micron pore size. 
     In some embodiments, a drug delivery device is the second important aspect of the antibody formulation. In other embodiments, the drug delivery device is sterile. In other embodiments, the drug delivery device is a vial, ampoule, syringe, injection pen or an intravenous (i.v) bag. 
     In a non-limiting embodiment of the present disclosure, functional characterization comprises performing experiments to understand the kinetics and dynamics of binding of an anti-CLEC2D antibody using techniques that include, but are not limited to, ELISA, BIAcore, flow cytometry, western-blot and imaging, amongst other techniques that are well known in the art. Further CLEC2D-CD161 interaction sites are mapped, and then monitored and validated through flow cytometry based binding experiments. 
     In a non-limiting embodiment of the present disclosure, monoclonal antibodies function through various mechanisms to destroy tumor cells with an ultimate effect of priming either the innate or adaptive arm of the immune system. The effector functions include complement-dependent cytotoxicity (CDC), antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP). One non-limiting approach employed in the methods disclosed herein is to enhance the efficacy of therapeutic antibodies by modifying the immunoglobulin constant region. An example of such an antibody includes an anti-CLEC2D antibody which consists of a variable region (novel heavy chain and light chain regions) and may consist constant regions representing specific isotypes e.g., IgG1, IgG2, IgG4 or variants thereof, as described in this disclosure. Similarly, the unique variable region sequences could be used to develop antibody molecules with enhanced ADCC function or modified thermal stability as well as developing bispecific antibodies, ScFv molecules or any other antibody formats, as further described herein. 
     In a non-limiting embodiment of the present disclosure, the phrase “cytokines” may include chemokines, interferons, interleukins, lymphokines and tumor necrosis factors, which may be produced as an effect of the treatment of isolated antibody used against any of the cell lines related to a mentioned disease and/or combination thereof 
     In a non-limiting embodiment of the present disclosure, the phrase an “inducer” is a molecule that regulates gene expression. 
     An embodiment of the present disclosure comprises using methods and tools to understand interaction of genes associated with pathways such as NK-cell signature, IFN-γ production etc., in relation to a mode of action of selected antibody molecules. To exemplify, techniques such as western blot, flow cytometry, imaging through confocal microscopy and RT PCR are employed together to decipher the mechanistic impact of selected anti-CLEC2D antibody molecules, wherein the effect of various inhibitors against major signaling pathways are assessed in multiple cancer cells. In one embodiment, an IFN-γ release assay, CD107a+ expression, and/or cytoxicity assays are used to estimate the effectiveness of an anti-CLEC2D antibody. 
     In a non-limiting embodiment of the present disclosure, anti-tumor activity is assessed in huNOG-EXL mice bearing subcutaneous PC3 tumor xenograft, wherein the effect of a selected anti-CLEC2D antibody is monitored either alone or in combination with monoclonal antibody against a checkpoint target. In another embodiment, antibody dosage regimens are adjusted to obtain an optimum and desired anti-tumor response. In some embodiments, the phrases “parenteral administration” or related terms as used herein means mode of administration other than enteral and topical administration, usually by injection and includes, but is not limited to the following administration means, intramuscular, intravenous, intrarterial, intrathecal, intracapsular, intraorbital, intracardiac, intradermal, intraperitoneal, subcutaneous, subcuticular, intraspinal, epidural, intraasternal injection and infusion. 
     The following examples are presented in order to more fully illustrate the preferred embodiments of this disclosure. They should in no way be construed, however, as limiting the broad scope of this disclosure. 
     EXAMPLES 
     Example 1: Expression of Soluble CLEC2D Antigen 
     The antigen construct comprising an ecto-domain of CLEC2D, either wild type or mutated, was expressed in Chinese hamster ovary (CHO) cell line and purified as a soluble antigen. The CLEC2D ectodomain contains 5 cysteines with 2 putative disulphide bonds. The mutation H176C was carried out to introduce an additional disulphide bridge with the Cys163 amino acid to increase the stability and homogeneity of the expressed protein. The construct was developed with a C-term Histidine tag to facilitate the antigen purification process. 
     The extracellular domain of the CLEC2D (Q72-V191, H176C) antigen was codon optimized for both human and CHO expression system and the construct was synthesized. A specific signal sequence was used for secretion of the CHO expressed antigen. The CLEC2D gene sequence and appropriate signal sequence was cloned into the pCDNA3.1 mammalian expression vector ( FIG. 2A ). 
     CHO suspension cells at more than 90% viability were used for transfection of the expression plasmid encoding the CLEC2D gene. Cells were centrifuged at 1000-1400 rpm for 4-5 minutes. The spent media was decanted and the cells were re-suspended in 250 ml of OptiMEM I media. The CLEC2D expression plasmid was transfected using Lipofectamine LTX with Plus™ reagent. 500 μg of DNA was used with 1:3 DNA to transfection reagent ratio and 500 μl Plus&#39; reagent was used. DNA and Lipofectamine LTX complex was prepared in 250 ml OptiMEM I and incubated at 20-25° C. for 20 minutes for complex formation. The transfection mix was added slowly to the cell suspension. The cells were incubated for 5 hours at 37° C. in a 5% CO 2  shaker incubator at 100-120 RPM. 500 ml of Power CHO2 CD growth media was added to the cells. The cells were incubated for 3 days at 37° C. in a 5% CO 2  shaker incubator at 100-120 RPM. Day 3 post transfection 200 ml Power CHO2 CD growth media containing 2 mM Glutamax was added. The cells were incubated at 37° C. in a 5% CO2 shaker incubator at 100-120 RPM. Day 6 post transfection, cell culture supernatant was harvested by centrifugation at 1400-2000 rpm for 10-15 minutes. 
     The cell harvest was centrifuged and filtrated to remove cell debris. The clear supernatant was loaded onto pre-equilibrated Ni Sepharose FF C10 column. Subsequently the column was washed with 50 mM and 100 mM Imidazole solution sequentially followed by single-step elution of His-tagged CLEC2D protein with 500 mM imidazole. Multiple fractions were collected and buffer exchanged to 1× phosphate buffered saline (PBS) pH 7.4. 
     Purified CLEC2D antigen was analysed through SDS-PAGE. The human CLEC2D sequence has two putative N-glycosylation sites N95 and N147. The aberrant mobility in SDS-PAGE was speculated to be due to differential N-glycosylation pattern. Purified CLEC2D antigen was de-glycosylated using PNGase enzyme and appeared to be as single band on expected molecular weight as judged by SDS-PAGE analysis ( FIGS. 2B-2F ). Subsequently purified CLEC2D antigen was analysed by western blot experiments using a commercially available anti-CLEC2D antibody. The purified CLEC2D antigen was also confirmed through ELISA with a commercially available anti-CLEC2D antibody. The oligomeric status of the protein was found to be a dimer using size exclusion chromatography experiments. Finally, N-terminal sequencing was carried out by Edman degradation method to confirm the antigen sequence. 
     Example 2: Screening of Antibody Gene Library Using Phage and Yeast Display Platforms 
     Screening of antibody gene libraries was carried out with by combining phage display and yeast display of the antibody libraries. Phage and yeast display platforms expressing a human antibody repertoire were used sequentially to identify novel antibody clones with higher affinity and specificity against CLEC2D antigen ( FIG. 3 ). For phage panning experiments against antigens, the magnetic bead based approach was adopted. Antigen coated on magnetic dynabeads were prepared and the efficiency of conjugation was &gt;90%. Phage antibody library was panned against the antigen coated beads to separate phage particles expressing anti-CLEC2D antibody clones. The selected phage particles were used to generate replicative form containing the heavy and light chain repertoire. Purified DNA was digested and ligated into yeast expression vector in two different plasmid constructs to generate antibodies in Fab format and ScFv format. 
     For magnetic bead conjugation with purified CLEC2D antigen, at first, dyna beads were weighed at a quantity ranging from 0.5 mg to 1.5 mg corresponding to ˜0.5-1.0×10 8  beads and dissolved into 0.1 M sodium phosphate buffer, pH 7.4. This suspension was vortexed for 30-60 seconds followed by incubation at room temperature for 10-15 minutes with continuous rotation. The suspension was washed twice with 0.1 M sodium phosphate buffer and re-suspended again into 100 μL of 0.1 M sodium phosphate buffer. 5-10 μg of purified soluble CLEC2D antigen solution, (75-150 μL) was added to the bead suspension. Further, the suspension was mixed well before adding the 100 μL of 3 M ammonium sulfate solution. The mixture was incubated for 15-20 hours at 30-37° C. with slow tilt but continuous rotation. Post incubation the tube was placed on the magnet holder for 1 min for magnetic separation. The magnet holder (with the tube in place) was carefully turned upside-down twice to ensure no beads remain in the cap. The supernatant was removed and beads are washed four times with 1 mL 1×PBS containing BSA (0.05%). Finally, the beads are re-suspended in 100 μL of 1×PBS with BSA (0.05%) and are used in panning. 
     1 μL (˜10 6  number of beads) of bead alone and bead coated with CLEC2D antigen are mixed with commercial P4500/anti-CLEC2D antibody at amount of 0.1 μg followed by volume make up to 100 μL with 1×PBS containing 0.5% BSA. The mixture was incubated for 2 hrs on ice followed by a washing with 1×PBS containing 0.5% BSA. Anti-goat IgG conjugated with FITC at 1:400 dilution was added to the re-suspended beads in solution of 1×PBS containing 0.5% BSA to a volume of 100 μL before readings were taken. All the flow cytometry experiments were done using Accuri C6 flow cytometer while the analysis was done by using BD Accuri C6 software. Firstly, forward and side scatter data was seen to fix a gate followed by fluorescence reading through FLH1 filter. At least 5,000-10,000 data points are collected for each sample ( FIG. 4A ). 
     Phage panning experiment was started with inoculation of single colony from the freshly streaked TG1 bacterial plate into 3 ml LB medium followed by incubation at 37° C. until OD600≈0.9 and this was used for phage infection later. A phage naïve antibody library was thawed and the phage particles are precipitated with 250 μl (˜¼ of the phage suspension volume) PEG/NaCl solutions (20% PEG 8000 and 2.5 M NaCl) and incubated on ice for 30 minutes followed by centrifugation of the precipitated phage at 10,000×g for 10 minutes. The supernatant was discarded and the phage pellet was re-suspended in 200 μl PBS solution. Phage suspension (200 μl) was added to the bead conjugated with BSA and incubated on a rotator at room temperature for 2 hrs followed by adding the supernatant to bead conjugated with CLEC2D antigen and 10 μL of supernatant was kept aside for plaques assay later on. Phage suspension with conjugated bead with antigen was incubated on a rotator at room temperature for 2 hrs. The beads were washed two times with 1 ml 0.05% PBST (0.05% Tween-20 in PBS). Finally, magnetic beads bound with phage particle are re-suspended in 100 μl PBS. 10 μL of beads suspension was kept aside for plaques assay later on. The remaining 90 μl of the suspension was added to 2 ml of grown TG1 cells prepared earlier and the mixture was incubated at 37° C. for 1 h. Post incubation it was diluted into 10 ml LB medium containing ampicillin at a final concentration of 25 μg/ml. After two hours of incubation at 37° C. with constant shaking at 250 rpm, concentration of ampicillin was increased to a final concentration of 100 μg/ml. M13K07, helper phage, was mixed into the amplified TG1 cells with multiplicity of infection (MOI) of 10 and incubated at 37° C. for another 30 minutes. Helper phage-infected bacteria was spun down and the pellet was re-suspended into 10 ml of LB medium supplemented with 100 μg/ml ampicillin and 25 μg/ml kanamycin followed by incubation at 30° C. for 30 minutes to 100 minutes for phage amplification. The bacterial culture was pelleted down by centrifugation for 10 minutes at 10,000 g. The pellet was discarded and supernatant was used for precipitation of amplified phage molecules by adding PEG/NaCL solution to the supernatant (˜¼th volume of supernatant). The mixture was incubated for 30 min on ice, followed by spinning the precipitated phage at 10,000 g for 10 minutes. Supernatant was discarded and pellet was re-suspended in 1 ml of PBS. The Plaques assay was performed from the 10 μL of amplified phage suspension to estimate the amplified phage number while the remaining of the precipitated phage are stored with 50% glycerol at −80° C. freezer for long term storage. 
     Plaque assay was performed at every step to ensure the numbers of phage particles. A single colony from the TG1 bacterial plate was inoculated in bacteria in 3 ml LB medium and was grown at 37° C. until OD600≈0.9. 0.7% of agarose was prepared in purified water and stored at 50° C. in aliquots of 3 ml each in a 15 ml of falcon tubes. The phage supernatant and pellet were diluted at respective steps from 10 −1  to 10 −5 . 100 μl of diluted phage and 100 μl TG1 cells were added in to each of agarose aliquots and mixed followed by immediately spreading on LB Agar plate. The plates were incubated in 37° C. in an incubator for overnight. The plaque formation was observed and counted next day. The number of panned molecules was calculated based on number of plaques observed (Table 10). 
     
       
         
           
               
             
               
                 TABLE 10 
               
             
            
               
                   
               
               
                 Estimation of phage particle number at every step of panning  
               
               
                 process against CLEC2D antigen. 
               
            
           
           
               
               
            
               
                 Process Step 
                 Pfu/mL 
               
               
                   
               
               
                 Panning with BSA conjugated beads 
                 4 × 10 8   
               
               
                 Supernatant from BSA panning 
                 1 × 10 9   
               
               
                 CLEC2D binders 
                 4 × 10 6   
               
               
                   
               
            
           
         
       
     
     Single colony from the TG1 bacterial plate was inoculated into 20 ml LB medium at 37° C. until OD600 reaches ˜0.9. 200 μl of the precipitated panned phage suspension was inoculated into 2 ml TG1 cells (in 10 different tubes and each tube contains 2-5 ml of TG1 cells) followed by incubating the mixture at 37° C. with shaking for 1 hour. Volume in each tube was diluted into 10 ml LB medium containing 25 μg/ml Ampicillin. Following additional 2 hours of incubation at 37° C. with shaking at 220 rpm, ampicillin concentration was increased to a final concentration of 100 μg/ml and incubated further for 30 minutes to 100 min. Bacterial culture was spun down at 10,000 g for 10 minutes, and the pellet was used for DNA isolation through Qiagen midi prep as per manufacturer&#39;s protocol for further use. 
     Construction of heavy and light chain libraries in to yeast shuttle vectors in Fab format: 
     Isolated replicative form DNA of panned molecules along with the in-house yeast expression vector pZB003 (MTCC 25127) designated for light chain incorporation are digested with HindIII and AscI followed by ligation and transformation individually into TG1, highly competent cells. Likewise, heavy chain pool (sourced from isolated replicative form) and the respective vector pZB002 (MTCC 25126) are digested with NcoI and NotI followed by ligation and transformation into TG1, highly competent cells. Transformation efficiency obtained for both heavy and light chain panned library are &gt;10 7  cfu. Obtained transformed colonies for both heavy and light chain libraries are checked for insert release using NcoI/NotI for heavy chain ( FIG. 4B ) and HindIII/AscI for light chain ( FIG. 4C ) before they are scraped for glycerol stock preparation. Insert release for both the chains confirmed the presence of panned variable heavy and light chain-kappa molecules. Glycerol stocks are stored at −80° C. for future use. Tables 10, 11 and 12 provide for components applicable in constructing libraries in yeast vectors. 
     
       
         
           
               
               
               
             
               
                   
                 Table 11 
               
               
                   
                   
               
               
                   
                 Components 
                 Amount/Volume 
               
               
                   
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 DNA 
                 20  
                 ug 
               
               
                   
                 NcoI 
                 4  
                 uL 
               
               
                   
                 NotI 
                 4  
                 uL 
               
               
                   
                 CutSmart Buffer 
                 10 
                   
               
            
           
           
               
               
               
            
               
                   
                 Water 
                 Respective Volume 
               
            
           
           
               
               
               
               
            
               
                   
                 Total 
                 100  
                 uL 
               
               
                   
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
             
               
                   
                 TABLE 12 
               
               
                   
                   
               
               
                   
                 Components 
                 Amount/Volume 
               
               
                   
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 DNA 
                 20 
                 ug 
               
               
                   
                 HindIII 
                 4 
                 uL 
               
               
                   
                 AscI 
                 4 
                 uL 
               
               
                   
                 CutSmart Buffer 
                 10 
                   
               
            
           
           
               
               
               
            
               
                   
                 Water 
                 Respective Volume 
               
            
           
           
               
               
               
               
            
               
                   
                 Total 
                 100 
                 uL 
               
               
                   
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
             
               
                   
                 TABLE 13 
               
               
                   
                   
               
               
                   
                 Components 
                 Amount/Volume 
               
               
                   
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 Vector 
                 100  
                 ng 
               
               
                   
                 Insert 
                 100  
                 ng 
               
               
                   
                 T4 DNA ligase 
                 0.5 
                 uL 
               
               
                   
                 T4 DNA ligase Buffer 
                 2 
                 uL 
               
            
           
           
               
               
               
            
               
                   
                 Water 
                 Respective Volume 
               
            
           
           
               
               
               
               
            
               
                   
                 Total 
                 20 
                 uL 
               
               
                   
                   
               
            
           
         
       
     
     Construction of heavy and light chain libraries in to yeast shuttle vectors in ScFv format: 
     ScFv format comprises of transfer of light chain (kappa repertoire originated from panned phage against CLEC2D antigen) into pZB004.4 vector between NdeI and AscI restriction sites followed by generation of a pool of light chain ScFv library. Subsequently the library was confirmed with restriction digestion confirmation followed by transfer of panned heavy chain pool into ScFv-light chain library between NcoI and NotI restriction enzymes. This final library was used as ScFv library of panned molecules which will be further transformed, sorted and screened in yeast expression system. Isolated replicative form DNA of panned molecules along with the in-house ScFv yeast expression vector are digested with NdeI and AscI followed by ligation and transformation individually into TG1, highly competent cells. 
     Obtained transformed colonies for light chain libraries are checked for insert release using NdeI/AscI before they are scraped for glycerol stock preparation. Insert release confirmed the presence of panned molecules. Glycerol stocks are stored at −80° C. for future use. Plasmid isolation was carried out using Qiagen midi prep kit which will be used for incorporation of heavy chain repertoire obtained from panning. 
     Likewise, heavy chain pool from isolated replicative form and the ScFv containing light chain library are digested with NcoI and NotI ( FIG. 4D ) followed by ligation and transformation into TG1, highly competent cells. Transformation efficiency obtained for both heavy and light chain panned library are &gt;10 7  cfu. Colonies were confirmed with insert release for both heavy with NcoI/NotI and light chains with NdeI/AscI ( FIG. 4E ). 
     Tables 13, 14 and 15 provide for components applicable in constructing libraries in yeast expression vector. 
     
       
         
           
               
               
               
             
               
                   
                 TABLE 14 
               
               
                   
                   
               
               
                   
                 Components 
                 Amount/Volume 
               
               
                   
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 DNA 
                 20 
                 ug 
               
               
                   
                 NdeI 
                 4 
                 uL 
               
               
                   
                 AscI 
                 4 
                 uL 
               
               
                   
                 CutSmart Buffer 
                 10 
                   
               
            
           
           
               
               
               
            
               
                   
                 Water 
                 Respective Volume 
               
            
           
           
               
               
               
               
            
               
                   
                 Total 
                 100 
                 uL 
               
               
                   
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
             
               
                   
                 TABLE 15 
               
               
                   
                   
               
               
                   
                 Components 
                 Amount/Volume 
               
               
                   
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 DNA 
                 20 
                 ug 
               
               
                   
                 NcoI 
                 4 
                 uL 
               
               
                   
                 NotI 
                 4 
                 uL 
               
               
                   
                 CutSmart Buffer 
                 10 
                   
               
            
           
           
               
               
               
            
               
                   
                 Water 
                 Respective Volume 
               
            
           
           
               
               
               
               
            
               
                   
                 Total 
                 100 
                 uL 
               
               
                   
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
             
               
                   
                 TABLE 16 
               
               
                   
                   
               
               
                   
                 Components 
                 Amount/Volume 
               
               
                   
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 Vector 
                 100 
                 ng 
               
               
                   
                 Insert 
                 100 
                 ng 
               
               
                   
                 T4 DNA ligase 
                 0.5 
                 uL 
               
               
                   
                 T4 DNA ligase Buffer 
                 2 
                 uL 
               
            
           
           
               
               
               
            
               
                   
                 Water 
                 Respective Volume 
               
            
           
           
               
               
               
               
            
               
                   
                 Total 
                 20 
                 uL 
               
               
                   
                   
               
            
           
         
       
     
     DNA isolated in large scale was checked for restriction digestion, before transferred for yeast transformation. Post confirmation through restriction digestion at least 10 independent clones containing variable heavy and light-kappa chains for each of formats were sent for sequencing reactions. The sequencing results have been summarized in terms of productive heavy and light-kappa chains in the following Table 17. 
     
       
         
           
               
             
               
                 TABLE 17 
               
             
            
               
                   
               
               
                 summarizes the percentage productivity  
               
               
                 for variable heavy chain and light-kappa 
               
               
                 chain as estimated from sequencing  
               
               
                 reactions carried out from independent clones. 
               
            
           
           
               
               
               
               
            
               
                 Antigen 
                 Format 
                 Chain Type 
                 Productivity 
               
               
                   
               
               
                 CLEC2D 
                 Fab 
                 Variable heavy chain pool 
                 81% 
               
               
                   
                   
                 Variable Light chain Pool 
                 80% 
               
               
                   
                 ScFv 
                 Heavy and Light chain 
                 85% 
               
               
                   
                   
                 repertoire 
               
               
                   
               
            
           
         
       
     
     As detailed above, phage antibody library was panned against the CLEC2D antigen coated beads in order to eliminate non-specific binders. The selected phage particles were used to generate replicative form containing the heavy and light chain repertoire. This method was devoid of any PCR based approached which might introduce unwanted biasness towards the panned pool of molecules. Purified replicative form of DNA was digested and ligated into yeast expression vector in two different plasmid constructs to generate antibody in Fab format and ScFv format, wherein the cloning efficiency was estimated to be &gt;95% and the efficiency of TG1 cells transformation was more than 10 7  cfu. These parameters were essential to meet to ensure complete capturing of panned diversity. 
     Subsequently, yeast DNA libraries in both formats i.e., ScFv and Fab, were transformed into yeast cells. Transformed yeast cells were checked for heavy chain, light chain and Fab molecule expression. Surface expression of antibody genes were analysed with multiple tags such as FLAG, c-Myc and (His) 6 -tag and V5-tag for heavy chains and light chains, respectively. Flow cytometry based sorting was carried out to isolate yeast cells expressing antibody sequences showing specific antigen binding ( )). Flow sorting of yeast cell populations were repeated 2-3 times to enrich antibody clones with higher affinity towards labelled CLEC2D antigen. 
     Generation of Yeast ScFv Library 
     EBY100 strain ( S. cerevisiae  cells) was grown for overnight in to 5 ml YPD media on a platform shaker at 220 rpm and 30° C. The next morning, an aliquot of the overnight culture was inoculated into 100 ml YPD media at OD600˜0.3. The inoculated cells continued to grow on a platform shaker at 30° C. and 220 rpm until OD600 reached to ˜1.6 (usually after 5 hours-6 hours). Yeast cells were collect by centrifugation at 3000 rpm for 3 minutes and the media was removed. The cell pellet was washed twice with 50 ml ice cold water and once by 50 ml of ice cold electroporation buffer (1 M Sorbitol/1 mM CaCl2). The yeast cells were condition by re-suspending the cell pellet in 20 ml (0.1 M LiAc/10 mM DTT) and shaking at 220 rpm in a culture flask for 30 minutes at 30° C. The conditioned cells were collected by centrifugation, washed once with 50 ml ice-cold electroporation buffer and re-suspended the cell pellet in 100 μl to 200 μl electroporation buffer to reach a final volume of 1 ml. 
     This corresponds to approximately 1.6×10 9  cells/ml and is sufficient for 2 electroporation reactions of 400 μl each. The cells were kept on ice until electroporation. 400 μl electro competent cells were gently mixed with required amount of plasmid DNA and transferred to a pre-chilled Bio-Rad GenePulser cuvette (0.2 cm electrode gap) and kept on ice for 5 min until electroporation. The cells were electroporated at 2.5 kV and 25 μF. Electroporated cells were transferred from each cuvette into 8 mL of 1:1 mix of 1 M sorbitol: YPD media, and incubated on a platform shaker at 220 rpm and 30° C. for 1 hour. Cells were collected by centrifugation and resuspended in SDCAA media. 10-fold serially diluted cells were prepare from the cell suspension and 100 μl of 10-3 and 10-4 diluted cells were plated onto selective plates (SDCAA plates) and incubated at 30° C. incubator for 3-4 days. Library size was determined from the colony counts after 3-4 days ( FIG. 5A ). After 3-4 days colonies were observed on SDCAA plate. Finally, 20% glycerol stock of the yeast ScFv antibody library was prepared by scrapping yeast cells and stored at −80° C. 
     Generation of Yeast haploid antibody libraries for the development of Fab antibody library 
     Transformation was performed according to manufacturer&#39;s (Zymo Research) protocol with minor modifications. Briefly, EBY100ura3Δ4.03 strain ( S. cerevisiae  cells) and YVH10 were grown for overnight in 5 ml YPD media on a platform shaker at 220 rpm and 30° C. The OD600 value of overnight culture was checked and the overnight culture was re-inoculated into 50 ml YPD medium with starting OD600-0.4, until OD600 reached ˜1.0-1.2 at 30° C., in incubator shaker with 220 rpm. Yeast cells were collected by centrifugation at 3000 rpm for 3 minutes and the media was removed. Cell pellet was washed with 10 ml EZ1 solution followed by centrifugation at 3000 rpm for 10 min. Then, cell pellet was resuspended in to 600 μl of EZ2 solution and further incubated at RT for 5 min. 200 μl of EZ2 solution containing competent yeast cells was mixed with appropriate amount of plasmid DNA and 500 μl of EZ3 solution. Above mix of competent yeast cells and DNA was incubated at 30° C. for 1 hr and 30 min. The yeast cells were centrifuged at 2400 rpm for 5 min. 200 μl of the supernatant was discarded and the cell pellet resuspended in the remaining supernatant. 
     10-fold serially diluted cells from the cell suspension was prepared and 100 μl of 10-3 diluted cells was plated on selective plates and incubated at 30° C. incubator for 3-4 days. EBY100ura3Δ4.03 transformed with heavy chain antibody library was selected on tryptophan drop out glucose medium. However, YVH10 strain with light chain antibody library was selected on uracil drop out medium. Library size was determined from the colony counts after three days and estimated to be ˜10 5 . ( FIG. 5A ) 20% glycerol stock of the haploid yeast antibody libraries was prepared and stored at −80° C. 
     Generation of diploid yeast Fab library through yeast mating 
     The two haploid yeast strains with heavy and light chain libraries having different mating types were scraped with amino acid drop out glucose media. OD600 of the both haploid cell cultures was checked. About 1 OD600 of each culture was taken in 1.5 ml microfuge tube and spun at 13000 rpm for 3-5 min. Discard the supernatant then added 100 μL of purified water in each pellet and mix them together. Plated mixed yeast cultures onto YPD plate and incubated for 5-6 hrs at 30° C. Yeast cells from the YPD plate after 5-6 hrs were scraped and OD600 of the scraped yeast cells was monitored. The scraped culture were inoculated into ura trp double drop out glucose media with starting OD600 of 0.1 and incubated for at least 24 hrs at 30° C., 220 rpm (for diploid enrichment). 
     OD600 of enriched diploid culture was monitored and dilutions were prepared from enriched culture containing approximately 500 and 1000 cells. The dilutions were plated onto single and double drop out amino acid glucose agar plates and incubated at 30° C. for 2-3 days. Diploid library was selected on ura trp double drop out glucose plate. 20% glycerol stock of the remaining enriched diploid culture was prepared and stored at −80° C. Percentage mating efficiency was calculated as the number of diploid colonies grown in the double drop out media plates divided by the number of total colonies grown in the single drop out plates. Yeast fab antibody library was generated through yeast mating ( FIG. 5C ). 
     Flow sorting of Yeast Fab and ScFv library 
     The yeast samples were inoculated into 3 ml of SDCAA media and incubated yeast cell for overnight at 30° C., 220 rpm. Next day, the OD600 value of the inoculated cultures was monitored by diluting of 1:10. 0.3 OD600 cells of the yeast samples was inoculated into 20 ml 2×SGCAA media and incubated for 48 hrs in incubator shaker at 20° C., at 220 rpm. The OD600 of the induced culture was monitored by diluting 1:10 after 48 hrs. About 0.1 OD600 cells was taken from grown yeast cultures into 1.5 ml tube and spun at 13,000 rpm for 2 minutes. The supernatant was discarded and the pellet was washed by adding 100 μl of 1×PBS and 241 pun at 13,000 rpm for 2 minutes. The supernatant was discarded again. 200 μl of primary antibody or biotinylated antigen with an appropriate concentration was added in yeast cell pellet and incubated for 45 min on rotation at RT. After incubation, the cells were spun at 13,000 rpm for 2 min and the supernatant was discarded. Cell pellet was washed twice by adding 200 μl of PBS containing 0.1% BSA and spun at 13,000 rpm for 2 minutes and the supernatant was discarded. 200 μl of secondary antibody with an appropriate concentration was added in to yeast cell pellet and incubated for 30 min on ice. After incubation, the cells were spun at 13,000 rpm for 2 minutes and the supernatant was discarded. The pellet was washed thrice by adding 200 μl of 1×PBS containing 0.1% BSA and spun at 13,000 rpm for 2 minutes. 300 μL of 1×PBS was added in yeast cell pellet and samples were analysed through flow sorter ( FIGS. 5D and 5E ). Concentrations for primary, secondary antibodies and biotinylated antigen are presented in Table 18. 
     
       
         
           
               
               
               
             
               
                 TABLE 18 
               
               
                   
               
               
                 Format of 
                   
                   
               
               
                 antibody  
                 Primary antibody  
                 Secondary antibody  
               
               
                 library 
                 (Concentration) 
                 (Concentration) 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
            
               
                 Expression of library 
               
            
           
           
               
               
               
            
               
                 ScFv 
                 Myc Tag polyclonal  
                 Goat anti-Chicken IgY  
               
               
                   
                 (5 μg/ml) 
                 (H + L) Secondary 
               
               
                   
                   
                 Antibody, Alexa Fluor  
               
               
                   
                   
                 488 (5 μg/ml) 
               
               
                 Fab 
                 V5 Tag (5 μg/ml) 
                 Goat anti-Chicken IgY  
               
               
                   
                   
                 (H + L) Secondary 
               
               
                   
                   
                 Antibody, Alexa Fluor  
               
               
                   
                   
                 488 (5 μg/ml) 
               
            
           
           
               
            
               
                 Binding of library  
               
            
           
           
               
               
               
            
               
                 ScFv 
                 Biotinylated CLEC2D  
                 Streptavidin, Alexa Fluor ™  
               
               
                   
                 antigen (250 nM for 
                 633 conjugate (5 μg/ml) 
               
               
                   
                 flow resort-1, 100 nM for 
                   
               
               
                   
                 flow sort-1, 50 nM 
                   
               
               
                   
                 for flow resort-2,)  
                   
               
               
                 Fab 
                 Biotinylated CLEC2D  
                   
               
               
                   
                 antigen (250 nM for 
                   
               
               
                   
                 flow resort-1, 100 nM for 
                   
               
               
                   
                 flow sort-1, 50 nM  
                   
               
               
                   
                 for flow resort-2,) 
               
               
                   
               
            
           
         
       
     
     Individual clone screening from sorted/resorted ScFv or sorted/resorted Fab pool 
     Similar flow staining protocol was used as discussed during flow sorting for individual clone screening. About 1000 colonies were screened through flow cytometry for expression and antigen binding ( FIGS. 5F, 5G, and 5H ). These clones were selected on the basis of &gt;2% and &gt;5% positive for both binding and expression in case of Fab and ScFv clones respectively. 
     In addition selected pool of antibody genes as obtained from sorting against soluble CLEC2D antigen were subjected for next generation sequencing. This exercise was carried out for both ScFv and Fab format of antibody gene pools. As exemplified, Seq IDs SEQ ID 44; SEQ ID 45; SEQ ID 42; SEQ ID 1; SEQ ID 73; SEQ ID 21; SEQ ID 35; SEQ ID 58; SEQ ID 7; SEQ ID 260; SEQ ID 261; SEQ ID 258; SEQ ID 217; SEQ ID 289; SEQ ID 237; SEQ ID 251; SEQ ID 274; SEQ ID 223 were enriched at the final sorted round ranging from 2.5 fold to 7 fold, as applicable to clones screened in Fab format, while the clones screened in ScFv format were enriched to fold ranging from 2 fold to 106 fold, to an approximate. The fold enrichment estimation was carried out through number of gene copies seen at every round of sorting. This further supports the fact that antibodies against CLEC2D antigen were screened, isolated and identified via a robust platform comprising naïve antibody library screened phage and yeast display technologies. 
     Finally, individual yeast clones were identified using flow cytometry assays. Subsequently, peer group antibody gene sequencing was carried out and novel antibody sequences were taken for further cloning to mammalian gene expression vectors. Yeast plasmid DNA was isolated from selected yeast clones, existing in both Fab or ScFv formats, using Zymoprep Yeast Plasmid miniprep kit—The variable region of heavy and light chains in selected yeast clones with Fab format were amplified using vector specific primer followed by sequencing. While for clones in ScFv format, isolated plasmids from yeast colonies were subsequently transformed into NEB-alpha cells for larger production. The isolated plasmids from NEB-alpha cells were sent for sequencing confirmation.  FIG. 5H  summarizes percentage binding of monoclonal antibody clones with CLEC2D antigen, as determined by flow cytometry. The data suggest at least about 80% of the monoclonal antibody clones revealed detectably and specifically binding to CLEC2D antigen. 
     All sequence identifiers and relevant sequence identity analysis are described in Table 19, which lists antibody clones for variable heavy chains, and Table 20, which lists antibody clones for variable kappa light chains. 
     
       
         
           
               
             
               
                 TABLE 19 
               
             
            
               
                   
               
               
                 SEQ ID NOs of VH Sequences of Anti-CLEC2D 
               
            
           
           
               
               
            
               
                 % Sequence 
                   
               
               
                 Identity 
                 Variable heavy chain Sequence ID NOs 
               
               
                   
               
               
                 35%-40% 
                 SEQ ID NO: 33; SEQ ID NO: 34; SEQ ID NO: 87; SEQ ID NO: 82; SEQ ID 
               
               
                   
                 NO: 104 
               
               
                 40%-45% 
                 SEQ ID NO: 11; SEQ ID NO: 35; SEQ ID NO: 86; SEQ ID NO: 22; SEQ ID 
               
               
                   
                 NO: 69; SEQ ID NO: 41; SEQ ID NO: 3; SEQ ID NO: 66; SEQ ID NO: 37; 
               
               
                   
                 SEQ ID NO: 56; SEQ ID NO: 21; SEQ ID NO: 38; SEQ ID NO: 90; SEQ ID 
               
               
                   
                 NO: 100; SEQ ID NO: 18; SEQ ID NO: 20; SEQ ID NO: 83; SEQ ID NO: 1; 
               
               
                   
                 SEQ ID NO: 19 
               
               
                 45%-50% 
                 SEQ ID NO: 105; SEQ ID NO: 101; SEQ ID NO: 4; SEQ ID NO: 72; SEQ ID 
               
               
                   
                 NO: 28; SEQ ID NO: 64; SEQ ID NO: 25; SEQ ID NO: 60; SEQ ID NO: 55; 
               
               
                   
                 SEQ ID NO: 52; SEQ ID NO: 27; SEQ ID NO: 43; SEQ ID NO: 70; SEQ ID 
               
               
                   
                 NO: 71; SEQ ID NO: 14; SEQ ID NO: 85; SEQ ID NO: 13; SEQ ID NO: 61; 
               
               
                   
                 SEQ ID NO: 42; SEQ ID NO: 39; SEQ ID NO: 10; SEQ ID NO: 49; SEQ ID 
               
               
                   
                 NO: 24; SEQ ID NO: 40; SEQ ID NO: 63; SEQ ID NO: 78; SEQ ID NO: 2; 
               
               
                   
                 SEQ ID NO: 94; SEQ ID NO: 5 
               
               
                 50%-55% 
                 SEQ ID NO: 97; SEQ ID NO: 16; SEQ ID NO: 76; SEQ ID NO: 9; SEQ ID 
               
               
                   
                 NO: 89; SEQ ID NO: 107; SEQ ID NO: 68; SEQ ID NO: 29; SEQ ID NO: 67; 
               
               
                   
                 SEQ ID NO: 74; SEQ ID NO: 32; SEQ ID NO: 81; SEQ ID NO: 106; SEQ ID 
               
               
                   
                 NO: 31; SEQ ID NO: 62; SEQ ID NO: 48; SEQ ID NO: 75; SEQ ID NO: 12; 
               
               
                   
                 SEQ ID NO: 102; SEQ ID NO: 54; SEQ ID NO: 80; SEQ ID NO: 26; SEQ ID 
               
               
                   
                 NO: 30; SEQ ID NO: 92; SEQ ID NO: 108; SEQ ID NO: 79 
               
               
                 55%-60% 
                 SEQ ID NO: 45; SEQ ID NO: 15; SEQ ID NO: 51; SEQ ID NO: 44; SEQ ID 
               
               
                   
                 NO: 73; SEQ ID NO: 36; SEQ ID NO: 77; SEQ ID NO: 50; SEQ ID NO: 6 
               
               
                 60%-80% 
                 SEQ ID NO: 9; SEQ ID NO: 53; SEQ ID NO: 95; SEQ ID NO: 23; SEQ ID 
               
               
                   
                 NO: 103; SEQ ID NO: 7 
               
               
                 80%-90% 
                 SEQ ID NO: 57; SEQ ID NO: 91; SEQ ID NO: 98; SEQ ID NO: 84; SEQ ID 
               
               
                   
                 NO: 58; SEQ ID NO: 88; SEQ ID NO: 96; SEQ ID NO: 47; SEQ ID NO: 17; 
               
               
                   
                 SEQ ID NO: 8 
               
               
                 90%-99% 
                 SEQ ID NO: 46; SEQ ID NO: 65; SEQ ID NO: 59; SEQ ID NO: 99 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 20 
               
             
            
               
                   
               
               
                 SEQ ID NOs of VL Sequences of Anti-CLEC2D 
               
            
           
           
               
               
            
               
                 % Sequence 
                   
               
               
                 Identity 
                 Variable kappa light chain Sequence IDs 
               
               
                   
               
               
                 50%-60% 
                 SEQ ID NO: 282; SEQ ID NO: 308; SEQ ID NO: 287; SEQ ID NO: 321; 
               
               
                   
                 SEQ ID NO: 236; SEQ ID NO: 265; SEQ ID NO: 270; SEQ ID NO: 275; 
               
               
                   
                 SEQ ID NO: 306; SEQ ID NO: 296; SEQ ID NO: 241; SEQ ID NO: 314; 
               
               
                   
                 SEQ ID NO: 223 
               
               
                 60%-65% 
                 SEQ ID NO: 254; SEQ ID NO: 289; SEQ ID NO: 238; SEQ ID NO: 268; 
               
               
                   
                 SEQ ID NO: 248; SEQ ID NO: 284; SEQ ID NO: 244; SEQ ID NO: 310; 
               
               
                   
                 SEQ ID NO: 243; SEQ ID NO: 285; SEQ ID NO: 220; SEQ ID NO: 255; 
               
               
                   
                 SEQ ID NO: 293; SEQ ID NO: 298; SEQ ID NO: 235; SEQ ID NO: 319; 
               
               
                   
                 SEQ ID NO: 245; SEQ ID NO: 224; SEQ ID NO: 291; SEQ ID NO: 277; 
               
               
                   
                 SEQ ID NO: 232 
               
               
                 65%-70% 
                 SEQ ID NO: 307; SEQ ID NO: 262; SEQ ID NO: 253; SEQ ID NO: 276; 
               
               
                   
                 SEQ ID NO: 323; SEQ ID NO: 234; SEQ ID NO: 261; SEQ ID NO: 312; 
               
               
                   
                 SEQ ID NO: 290 
               
               
                 70%-75% 
                 SEQ ID NO: 259; SEQ ID NO: 239; SEQ ID NO: 281; SEQ ID NO: 228; 
               
               
                   
                 SEQ ID NO: 217; SEQ ID NO: 227; SEQ ID NO: 251 
               
               
                 75%-80% 
                 SEQ ID NO: 231; SEQ ID NO: 250; SEQ ID NO: 260; SEQ ID NO: 226; 
               
               
                   
                 SEQ ID NO: 271; SEQ ID NO: 256; SEQ ID NO: 272; SEQ ID NO: 278; 
               
               
                   
                 SEQ ID NO: 302; SEQ ID NO: 320; SEQ ID NO: 295; SEQ ID NO: 292; 
               
               
                   
                 SEQ ID NO: 229; SEQ ID NO: 264; SEQ ID NO: 252; SEQ ID NO: 267; 
               
               
                   
                 SEQ ID NO: 304; SEQ ID NO: 300; SEQ ID NO: 311; SEQ ID NO: 324 
               
               
                 80%-85% 
                 SEQ ID NO: 222; SEQ ID NO: 258; SEQ ID NO: 219; SEQ ID NO: 313; 
               
               
                   
                 SEQ ID NO: 294; SEQ ID NO: 303; SEQ ID NO: 317; SEQ ID NO: 273; 
               
               
                   
                 SEQ ID NO: 266; SEQ ID NO: 315; SEQ ID NO: 257; SEQ ID NO: 288; 
               
               
                   
                 SEQ ID NO: 301; SEQ ID NO: 221; SEQ ID NO: 240; SEQ ID NO: 299; 
               
               
                   
                 SEQ ID NO: 247; SEQ ID NO: 263; SEQ ID NO: 274 
               
               
                 85%-99% 
                 SEQ ID NO: 218; SEQ ID NO: 249; SEQ ID NO: 230; SEQ ID NO: 279; 
               
               
                   
                 SEQ ID NO: 316; SEQ ID NO: 237; SEQ ID NO: 322; SEQ ID NO: 225; 
               
               
                   
                 SEQ ID NO: 318; SEQ ID NO: 233; SEQ ID NO: 305; SEQ ID NO: 280; 
               
               
                   
                 SEQ ID NO: 283; SEQ ID NO: 242; SEQ ID NO: 286; SEQ ID NO: 297; 
               
               
                   
                 SEQ ID NO: 309; SEQ ID NO: 246 
               
               
                   
               
            
           
         
       
     
     Example 3: Antibody Sequence Analysis to Identify Novel Antibody Clones 
     Variable regions of isolated antibodies for both heavy and light chains that specifically bind the CLEC2D antigen comprise of six hyper variable regions: 3 hyper variable regions from light chain (CDRL1, CDRL2, and CDRL3) and 3 hyper variable regions from heavy chain (CDRH1, CDRH2, and CDRH3). The length of the hypervariable regions may vary significantly, as shown for CDRH3, whose lengths have significant representation in the pool, ranging from 4-23 amino acids. The amino acid compositions were measured at every heavy chain CDRH3 length to understand the sequence variability of selected antibody genes against CLEC2D ( FIGS. 6A, 6B, 6C, and 6D ).The antibody sequences were analysed to determine uniqueness. Multiple sequence alignment tools were used to compare the antibody gene sequences with published antibody sequences in databases like IMGT, IgBLAST etc. 
     Further analysis of selected sequences identified antibody genes with de-amidation motifs, isomerization motifs, proteolytic cleavage motifs, N-linked glycosylation sites, plastic binding motifs, streptavidin binding motifs, human Fc binding motifs, mouse IgM binding motifs, bovine IgG motifs, proline rich motifs and cysteine rich motifs, etc. Such antibody genes were not deemed suitable for therapeutic monoclonal antibody development and therefore were not considered for further evaluation. Based on the extend of binding observed for antibody genes against soluble CLEC2D antigen at the level of individual yeast colony screening, top 40 binders, not limited to, were of further interest towards subsequent development. Only confirmed antibody gene sequences were taken for further cloning, expression and characterization. 
     Example 4: Cloning of Novel Antibody Genes 
     Error free antibody variable heavy and variable light chain regions were subsequently cloned into mammalian expression vectors, having various isotype backbones, either wildtype or mutants, originated from human, mouse and cynomolgus monkey species. Table 21 below summarizes relevants vectors developed towards cloning of identified anti-CLEC2D antibody genes and deposited to Microbial Type Culture Collection and Gene Bank (MTCC), India. 
     
       
         
           
               
               
               
               
             
               
                 TABLE 21 
               
               
                   
               
               
                   
                 Taxonomic 
                 Identification  
                 MTCC Number 
               
               
                 S. No. 
                 Designation 
                 Reference 
                 Assigned 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
            
               
                 1 
                 
                   E.coli 
                 
                 pZB005 
                 MTCC 25356 
               
               
                 2 
                 
                   E.coli 
                 
                 pZB006 
                 MTCC 25357 
               
               
                 3 
                 
                   E.coli 
                 
                 pZB007 
                 MTCC 25358 
               
               
                 4 
                 
                   E.coli 
                 
                 pZB008 
                 MTCC 25359 
               
               
                 5 
                 
                   E.coli 
                 
                 pZB009 
                 MTCC 25360 
               
               
                 6 
                 
                   E.coli 
                 
                 pZB010 
                 MTCC 25361 
               
               
                 7 
                 
                   E.coli 
                 
                 pZB011 
                 MTCC 25362 
               
               
                 8 
                 
                   E.coli 
                 
                 pZB012 
                 MTCC 25363 
               
               
                 9 
                 
                   E.coli 
                 
                 pZB013 
                 MTCC 25364 
               
               
                 10 
                 
                   E.coli 
                 
                 pZB014 
                 MTCC 25365 
               
               
                   
               
            
           
         
       
     
     As exemplified by, the mammalian expression vectors pZB007 (MTCC 25358) &amp; pZB008 (MTCC 25359) were designated and used for variable heavy chain and light chain gene cloning, respectively ( FIGS. 7A and 7B ). The vectors were custom designed and synthesized for the expression of antibody genes under the control of suitable promoter sequences. The plasmids carry a kanamycinR/puromycinR cassette driven by strong promoter and high-copy-number ColE1/pMB1/pBR322/pUC origin of replication for propagation ( FIGS. 7A and 7B ). 
     Sequence confirmed selected plasmids, as screened through phage and yeast display platform, against soluble CLEC2D antigen, using human naïve antibody library, were used as template for subsequent PCR amplification. PCR reactions were performed using sequence specific primers to amplify the selected clones having variable heavy and light chain regions. PCR reactions was carried out on an Eppendorf™ Mastercycler™ pro PCR System in 50 μL mixture volume consisting of 0.2 μM of each primer (Eurofins, India), 200 units of Phusion polymerase (NEB). Following an initial denaturation at 94° C. for 3 min, 30 cycles of 30 seconds denaturation at 94° C., and 50 seconds annealing at 60° C., 10 seconds primer extension at 72° C., 10 minutes final extension at 72° C. were performed. The PCR amplified product was extracted using QIAquick Gel Extraction kit. The plasmid vector pZB007 was linearized through restriction enzyme digestion by AscI and XbaI and for pZB008 with EcoRI and AscI. The inserts fragment and linearized vector were gel extracted using QIAGEN kit (20021).These purified vector and insert were used for recombination using Infusion HD Cloning kit (Takara, USA). Transformation of infusion reaction mixture into bacterial cells were performed. 100 μL aliquot of competent  E. coli  cells (Stellar) were taken from −80° C. freezer, thawed on ice for 5 minutes. 50% of recombination sample were added to the competent cells and gently mixed, incubated on ice for 20 minutes. Heat shock was given at 42° C. for 50 seconds in a dry bath. The vials were quick chilled on ice for 2 minutes. 0.950 mL of LB broth pre-warmed at 37° C. was added and incubated at 37° C., 220 rpm for 1 hour, in shaker incubator. 100 μL of the resulting culture was plated on LB agar media with kanamycin and incubated for overnight at 37° C. 
     Transformants containing specific DNA plasmid were inoculated in 5 mL of LB broth with Kanamycin and were incubated at 220 rpm, at 37° C. for overnight. Plasmid DNA was isolated from overnight grown culture using QIAGEN kit. Isolated clones were screened through restriction enzyme analysis performed using SpeI and XhoI enzymes and confirmed through sequencing and found to be error free. Sequence confirmed plasmid DNA from confirmed clones were purified at large scale using QIAprep Spin Midiprep kit (Qiagen) and in order to be used for subsequent transfection experimentation. 
     Example 5: Preparation of Anti-CLEC2D Antibody and Selection of CHO Expressed Novel Monoclonal Antibodies 
     Strategy to select novel monoclonal antibody clones 
     Owing to riveting design and properties of therapeutic antibody, it is required to be rational towards selecting a specific monoclonal antibody for further development. Moreover, generation, manufacturing and storage of antibodies are continuing to pose challenges as molecule properties such as pharmacokinetics, solubility, expression, viscosity and long-term stability are difficult to predict and understanding inter-parameter relationship is rather limited. Moreover considering the selected/identified diverse antibody genes which funnelled through antibody display platforms needed to be arranged through the ranking protocol. A comprehensive scoring function/methods was employed/developed based on existing sequencing data, exemplified by uniqueness, presence of certain motifs which could be not beneficial for further selection/development of clones; affinity towards CLEC2D antigen either in soluble form or as membrane bound format, and functionality; titre, yield, recovery, analytical profile, amongst others, either as independent or in combination, thereof. The clones would go through multiple rounds of checks on salient parameters in due course of development having a dynamic selection system which will effectively be employed towards selection of final clones. 
     CHO Cell Transfection with Full Length CLEC2D Gene for Cell Surface Expression. 
     In order to estimate the binding propensity of novel antibody genes identified against CLEC2D protein expressed on cell surface, a full length CLEC2D construct was synthesized. Native signal sequence was used for efficient surface expression on CHO cells. The full length CLEC2D gene sequence was cloned into the pCDNA3.1 mammalian expression vector ( FIG. 8A ). Subsequently the construct was transformed into neb-alpha and isolated in large quantity using Qiagen midi prep kit. CHO suspension cells with &gt;90% viability were transfected with a full-length CLEC2D gene expression plasmid. As exemplified, for 10 ml volume of transfection 1.25×10 6  cells/ml were taken, wherein CHO cells were centrifuged at 1000-1400 rpm for 4-5 minutes. The spent media was decanted, and the cells were re-suspended in 2.5 ml of OptiMEM I media. DNA constructs were transfected using Lipofectamine LTX with Plus&#39; reagent. 5-10 of DNA was used with 1:3 to 1:6 DNA to transfection reagent ratio and 5-10 μl Plus™ reagent was used. DNA and Lipofectamine LTX complex was prepared in 2.5 ml OptiMEM I and incubated at 20-25° C. for 5 minutes for complex formation. The transfection mix was added slowly to the cell suspension. The cells were incubated for 4-6 hours at 37° C. in a 5% CO2 shaker incubator at 100-120 RPM. 5 ml of Power CHO2 CD growth media was added to the cells. The cells were incubated at 37° C. in a 5% CO2 shaker incubator at 100-120 RPM. 2-4 days post transfection 2 ml Power CHO2 CD growth media was added and Glutamax was added from 200 mM stock to achieve a final concentration of 2 mM. The cells were incubated at 37° C. in a 5% CO2 shaker incubator at 100-120 RPM. Cells were analyzed for surface antigen binding by flow-cytometry on day 3, day 4 and day 5 after transfection. Transfected CHO cells with full length constructs will be known here onwards as C4548, unless mentioned otherwise elsewhere. 
     C4548 cells, transiently expressing full-length membrane anchored CLEC2D antigen were validated through both flow cytometry and confocal microscopy by using commercial anti-CLEC2D antibody. Approximately, 50,000-100,000 cells were taken in a 96-well U bottom plate. 1-5 μg of commercial anti-CLEC2D Antibody (4C7) (Cat # H00029121-M01; Novus Biologicals) in 100 μl assay buffer was added to the both untransfected CHO and C4548 transfected with full length CLEC2D surface antigen construct and incubated for 1 hr at room temperature in DPBS with 1-2% BSA. After 1 hr incubation, the plate was centrifuged at 1000-1400 rpm for 3-5 minutes. The cells were further washed twice with 200 μl of 0.1% BSA solution. 1 in 100 dilution of secondary antibody i.e., anti-mouse Alexa 488 (Thermo Fisher Scientific) was added. Subsequently, the plates were incubated at room temperature for 30 minutes in dark. The wells were washed twice with 0.1% BSA solution and analyzed by flow cytometry. Cell surface binding of the monoclonal antibody was estimated by comparing increase in fluorescence signal between CLEC2D expressing CHO cells and un-transfected CHO cells. Surface expression of CLEC2D antigen was optimum on day 4 to day 5 on C4548 transfected CHO cells ( FIG. 8B ). 
     For confocal microscopy experimentation, 250 μl of 12 μg/ml Poly D Lysine was added per well and incubated overnight at 37° C. Chambers were washed twice with 500 μl of DPBS and stored in 2° C. to 8° C. Un-transfected and CLEC2D antigen expressing CHO cells, C4548, were used, wherein cell count and viability data was collected using vi-cell Beckman coulter. 50,000 cells were seeded in 500 μl growth media (Power CHO2 with 4 mM Glutamine+1% Penstrep) with 10% FBS per well. All the cells were incubated in humidified 5% CO2 incubator at 37° C. for 2 days prior to the experiment. Further, cells were washed with 1×PBS then fixed in 2% formaldehyde in PBS for 5 minutes at room temperature (RT). Cells were then rinsed twice with 1×PBS followed by blocking with 5% BSA for 1 hr at RT. After 1 hour incubated with diluted primary antibody i.e., anti-CLEC2D Antibody (4C7) (2 μg) for 1 hour at RT followed by washing for at least three times in PBS and then incubated with the anti-mouse Alexa 488 (Thermo Fisher Scientific), secondary antibody, (2 μg) for 1 hour at RT. Cell nuclei were stained using DAPI (1:1000 for 5 min at RT). Cells were then rinsed thrice in 1×PBS and remained submerged in PBS until imaging. Immunofluorescence microscopy was performed on Olympus FV3000-4 laser scanning confocal microscope with a 60× magnification with 1.35-NA objective. Cells were imaged at 16 hrs after treatment by using appropriate wavelengths (For DAPI, λex 405 nm and λem 430-470 nm; for Alexa 488, λex 488 nm and λem 510-530 nm. Images were analyzed with Fiji ImageJ software. 
     As confirmed by microscopy images, the surface expression of CLEC2D on C4548 cells, were observed as distributed on cell surface while untransfected CHO cells fails to provide any anti-CLEC2D antibody dependent signal under microscopy ( FIG. 8C ). 
     CHO Cell Transfection to Express Novel Anti-CLEC2D Monoclonal Antibody Clones 
     Antibody heavy chain and light chain genes were expressed using mammalian gene expression vectors with appropriate signal sequences for secretion of correctly folded monoclonal antibodies into culture media. CHO suspension cells at more than 90% viability were transfected for antibody gene expression. CHO cells, at 1.25×10 6  cells/ml, were centrifuged at 1000-1400 rpm for 4-5 minutes. The spent media was decanted. The cells were re-suspended in 25 ml of OptiMEM I media. Antibody heavy chain and light chain gene expressing plasmids were co-transfected at various stoichiometry (such as, 1:2, 1:3, 1:4, 2:3, 3:1, 4:1 etc.) using Lipofectamine LTX with Plus™ reagent. 50-100 pg of DNA was used with 1:3 to 1:6 DNA to transfection reagent ratio and 50-100 μl Plus™ reagent. DNA and Lipofectamine LTX complex was prepared in 25 ml OptiMEM I and incubated at 20-25° C. for 5 minutes for complex formation. The transfection mix was added slowly to the cell suspension. The cells were incubated for 4-6 hours at 37° C. in a 5% CO2 shaker incubator at 100-120 RPM. 50 ml of Power CHO2 CD growth media was added to the cells. The cells were incubated at 37° C. in a 5% CO2 shaker incubator at 100-120 RPM. 2-4 days post transfection 20 ml Power CHO2 CD growth media was added, and Glutamax was added from 200 mM stock to achieve final concentration of 2 mM. The cells were incubated at 37° C. in a 5% CO2 shaker incubator at 100-120 RPM. Day 6 post transfection, cell culture supernatant (50 mL) was harvested by centrifugation at 1400-2000 rpm for 10-15 minutes. 
     Screening of CHO expressed monoclonal antibodies using cell surface binding: transient 
     Subsequently, harvested culture supernatant of 50 mL containing secreted novel anti-CLEC2D antibody clones were subjected to purification by Protein A affinity chromatography using cellgravity columns containing Mabselect SuRe resin (GE Healthcare). The method starts with Protein A column sanitization step wherein 3 Column Volume (CV) of 0.5M Sodium Hydroxide (NaOH) solution was passed at RT for 5 minutes followed by 8 Column Volume of Purified water. Subsequently, Protein A column was equilibrated with 3 CV of Protein A equilibration buffer comprises of 30 mM Sodium phosphate, 120 mM NaCl pH 7.0±0.2. 50 mL culture supernatant was loaded on equilibrated Protein A column while flow through was reloaded. This procedure was repeated twice. 3 CV of Protein A equilibration buffer washing was carried out followed by 3 CV of Protein A high salt buffer (30 mM Sodium phosphate, 1M NaCl pH 7.0±0.2) wash. 
     Further 3 CV of Protein A equilibration buffer was passed through the column followed by 4 CV of Protein A low pH buffer (30 mM Sodium phosphate, 50 mM NaCl pH 6.0±0.2) wash. Next, 5 CV of Protein A elution buffer (30 mM Sodium phosphate, 50 mM NaCl pH 3.0±0.1) was employed in order to elute the bound monoclonal anti-CLEC2D antibody. Further, Protein-A elute, containing antibody, was neutralized to pH ˜7.0 by adding appropriate amount of 1M Tris solution. 
     Following neutralization, Protein-A elute was concentrated and buffer exchanged into 1×PBS using Amicon 30 kDa cut-off concentrator. Protein sample was recovered from concentrator and concentration was measured by A280 using Nanodrop Biophotometer. Proteins were analysed by SDS-PAGE as shown in  FIG. 9A , under reducing and non-reducing condition. Subsequently, these protein samples were used for further experimentation. 
     As judged by quantitation, clones with product yield higher than 100 μg were shortlisted for the SDS-PAGE analysis to check the product quality under reducing and non-reducing conditions. Successively, clones with prominent bands in SDS-PAGE gels, as explained by, appearance of ˜150 kDa under non-reducing condition and ˜50 kDa (representing heavy chain) and ˜25 kDa (representing Light chain) under reducing condition were shortlisted for further analysis ( FIG. 9A ). In addition, purity was also judged through number of bands appeared along with the target protein and were also considered as criteria for selecting/shortlisting the clones. Proteins with more than 3 bands under non-reducing conditions similarly proteins with more than 1 band for heavy chain or light chain under reducing conditions were not taken into consideration. 
     Cell surface binding assay: through Flow cytometry and Confocal Microscopy 
     CHO suspension cells transiently expressing full-length membrane anchored CLEC2D antigen were used to screen antibody samples (cell culture supernatant and/or purified protein). 50,000-100,000 cells were taken in a 96-well U bottom plate. 100 μl of cell culture supernatant or 0.03-3 μg of purified antibody in 100 μl assay buffer was added to the CLEC2D expressing cells and incubated for 1 hr at room temperature in DPBS with 1-2% BSA. After 1 hr incubation, the plate was centrifuged at 1000-1400 rpm for 3-5 minutes. The cells were further washed twice with 200 μl of 0.1% BSA solution. 1 in 100 dilution of secondary antibody—goat anti human IgG FITC was added. Subsequently, the plates were incubated at room temperature for 30 minutes in dark. The wells were washed twice with 0.1% BSA solution and analyzed by flow cytometry. Commercially available anti-CLEC2D monoclonal Ab (Novus Biologicals) was used as a positive control and anti-mouse Alexa 488 (Thermo Fisher Scientific) was used as the secondary antibody. Cell surface binding of the monoclonal antibody was estimated by comparing increase in fluorescence signal between CLEC2D expressing CHO cells and un-transfected CHO cells. 
     In order to screen identified novel anti-CLEC2D monoclonal antibody, validated C4548 cells and PC3 cells were subjected for monitoring CLEC2D antigen binding through both flow cytometry and confocal microscopy. Prior to experimentation, cell count was taken by Vi-cell XR automated cell counter. Method of sample preparation for flow cytometry was as described above while ˜1-5 μg of purified Anti-CLEC2D antibody clones and reference positive control, respectively, to estimate the membrane bound CLEC2D binding on Untransfected CHO cells and C4548 cells. Cells were centrifuged at 1400-1500 rpm for 4-5 minutes. The pellet was re-suspended in 1 ml DPBS. 50,000 cells were aliquoted in each well of a 96 well plate. Both test samples and reference control was added to each well and incubated for 30-60 minutes at room temperature (25° C.). The plate was centrifuged at 1400-1500 rpm for 4-5 minutes, the supernatant was aspirated and cells were washed with 0.1% BSA in DPBS. 2.5 ml of 2% BSA was diluted to 50 ml with DPBS. Goat anti human IgG FITC conjugate was used as secondary antibody. 1:100 dilution of secondary antibody was prepared in DPBS and 100 μl was added to each well. The plate was incubated for 30 minutes at room temperature (25° C.) in dark. The cells were washed with 0.1% BSA and re-suspended in 100 μl of 1% BSA. Samples were analyzed by flow-cytometry ( FIG. 9B ). 
     Binding of test sample supernatant on un-transfected CHO cells was estimated and used for calculation of specific binding on C4548 cell surface using following formula: 
     
       
         
           
             
               Fold 
                
               
                   
               
                
               change 
                
               
                   
               
                
               in 
                
               
                   
               
                
               M 
                
               
                   
               
                
               F 
                
               
                   
               
                
               I 
             
             = 
             
               
                 
                   
                     
                       Median 
                        
                       
                           
                       
                        
                       FITC 
                        
                       
                         - 
                       
                        
                       A 
                        
                       
                           
                       
                        
                       of 
                        
                       
                           
                       
                        
                       test 
                        
                       
                           
                       
                        
                       sample 
                        
                       
                           
                       
                        
                       on 
                        
                       
                           
                       
                        
                       CHO 
                        
                       
                           
                       
                        
                       cells 
                     
                   
                 
               
               
                 
                   
                     
                       Median 
                        
                       
                           
                       
                        
                       FITC 
                        
                       
                         - 
                       
                        
                       A 
                        
                       
                           
                       
                        
                       of 
                        
                       
                           
                       
                        
                       test 
                        
                       
                           
                       
                        
                       sample 
                        
                       
                           
                       
                        
                       on 
                        
                       
                           
                       
                        
                       C 
                        
                       
                           
                       
                        
                       4548 
                        
                       
                           
                       
                        
                       cells 
                     
                   
                 
               
             
           
         
       
     
     For microscopy experimentation, PC3 cells were seeded, wherein, 250 μl of 12 μg/ml Poly D Lysine was added per well and incubated overnight at 37° C. Chambers were washed twice with 500 μl of DPBS and stored in 2° C. to 8° C. Adherent cell lines such as PC3, were trypsinized using 0.05% trypsin. Cell count and viability data was collected with hemocytometer using trypan blue staining. Cells were seeded at a density of 20000 cells/well with 500 μl growth media per well and incubated in humidified 5% CO2 incubator at 37° C. for 2 days prior to the experiment. Further, PC3 cells were washed with 1×PBS then fixed in 2% formaldehyde in PBS for 5 minutes at RT. Cells were then rinsed twice with 1×PBS followed by blocking with 5% BSA for 1 hour at RT. 
     After 1 hour incubated with diluted test antibody samples i.e., novel and unique anti-CLEC2D Antibody (at 2 μg) and commercial antibody as reference control, for 1 hr at RT followed by washing for at least three times in PBS and then incubated with the Alexa Fluor 488 goat anti-human IgG and anti-mouse Alexa 488 (Thermo Fisher Scientific), respectively as applicable, secondary antibody, (at 2 μg) for 1 hour at RT. Cell nuclei were stained using DAPI (1:1000 for 5 min at RT). Cells were then rinsed thrice in 1×PBS and remained submerged in PBS until imaging. Immunofluorescence microscopy was performed on Olympus FV3000-4 laser scanning confocal microscope with a 60× magnification with 1.35-NA objective. Cells were imaged at 16 hrs after treatment by using appropriate wavelengths (For DAPI, λex 405 nm and λem 430-470 nm; for Alexa 488, λex 488 nm and λem 510-530 nm. Images were analyzed with Fiji ImageJ software. Variation on CLEC2D antigen binding of mAbs tested and binding data is given as a rating of + (low binding) to +++ (high binding) (Table 19, and  FIG. 9C ). A variation on surface binding was observed and binding data is given as a rating of +(low binding) to +++ (high binding) on Table 22 As exemplified, surface binding was not detected with mAbC4252, whereas with antibodyC0610, low binding was observed thereby rated as (+) while other clones have showed differential yet significant surface binding. 
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 22 
               
               
                   
               
               
                   
                   
                   
                 Cell surface  
                   
               
               
                   
                   
                   
                 binding 
                   
               
               
                   
                   
                   
                 (Flow 
                   
               
               
                 SI. No. 
                 Codes 
                 Titer data 
                 cytometry) 
                 Imaging 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
               
            
               
                 1 
                 CO294 
                 More than 100 μg 
                 5.23 
                 +++ 
               
               
                 2 
                 C5397 
                 More than 100 μg 
                 4.88 
                 +++ 
               
               
                 3 
                 C5852 
                 More than 100 μg 
                 5.79 
                 +++ 
               
               
                 4 
                 C3566 
                 More than 100 μg 
                 10.21 
                 +++ 
               
               
                 5 
                 C7229 
                 More than 100 μg 
                 4.84 
                 + 
               
               
                 6 
                 C2901 
                 More than 100 μg 
                 5.1 
                 +++ 
               
               
                 7 
                 C4252 
                 More than 100 μg 
                 5.91 
                 Not detected 
               
               
                 8 
                 C4577 
                 More than 100 μg 
                 6.73 
                 +++ 
               
               
                 9 
                 C2685 
                 More than 100 μg 
                 9.78 
                 +++ 
               
               
                 10 
                 C5355 
                 More than 100 μg 
                 9.9 
                 ++ 
               
               
                 11 
                 C0610 
                 More than 100 μg 
                 8.62 
                 + 
               
               
                 12 
                 C8372 
                 More than 100 μg 
                 6.53 
                 + 
               
               
                 13 
                 C0694 
                 More than 100 μg 
                 8.43 
                 +++ 
               
               
                 14 
                 C6525 
                 More than 100 μg 
                 3.27 
                 + 
               
               
                 15 
                 C2771 
                 More than 100 μg 
                 7.94 
                 ++ 
               
               
                 16 
                 C0672 
                 More than 100 μg 
                 6.74 
                 + 
               
               
                 17 
                 C1063 
                 More than 100 μg 
                 1.96 
                 Not done 
               
               
                 18 
                 C4899 
                 More than 100 μg 
                 1.46 
                 Not done 
               
               
                 19 
                 C2302 
                 More than 100 μg 
                 7.72 
                 + 
               
               
                 20 
                 C3651 
                 10 μg-100 μg 
                 4.73 
                 Not done 
               
               
                 21 
                 C6803 
                 More than 100 μg 
                 6.17 
                 Not done 
               
               
                 22 
                 C7997 
                 More than 100 μg 
                 4.62 
                 + 
               
               
                 23 
                 C2060 
                 More than 100 μg 
                 3.91 
                 +++ 
               
               
                 24 
                 C0997 
                 More than 100 μg 
                 6.45 
                 +++ 
               
               
                 25 
                 C2119 
                 More than 100 μg 
                 2.64 
                 ++ 
               
               
                 26 
                 C3482 
                 More than 100 μg 
                 4.17 
                 Not done 
               
               
                 27 
                 C9652 
                 More than 100 μg 
                 2.17 
                 Not done 
               
               
                 28 
                 C4148 
                 More than 100 μg 
                 6.34 
                 +++ 
               
               
                 29 
                 C0800 
                 More than 100 μg 
                 7.28 
                 +++ 
               
               
                 30 
                 CO225 
                 More than 100 μg 
                 5.14 
                 +++ 
               
               
                 31 
                 C9767 
                 More than 100 μg 
                 4.24 
                 + 
               
               
                 32 
                 C9795 
                 More than 100 μg 
                 4.69 
                 +++ 
               
               
                 33 
                 C5870 
                 More than 100 μg 
                 2.6 
                 +++ 
               
               
                 34 
                 C7009 
                 More than 100 μg 
                 2.18 
                 +++ 
               
               
                 35 
                 C8637 
                 10 μg-100 μg 
                 Not done 
                 Not done 
               
               
                 36 
                 C5749 
                 10 μg-100 μg 
                 Not done 
                 Not done 
               
               
                 37 
                 C3558 
                 10 μg-100 μg 
                 Not done 
                 Not done 
               
               
                 38 
                 C5327 
                 10 μg-100 μg 
                 Not done 
                 Not done 
               
               
                 39 
                 C4137 
                 10 μg-100 μg 
                 Not done 
                 ++ 
               
               
                 40 
                 C6616 
                 10 μg-100 μg 
                 Not done 
                 +++ 
               
               
                   
               
            
           
         
       
     
     Based on all of above mentioned criteria and respective observed results covering biophysical and functional properties of isolated anti-CLEC2D antibodies, 9 unique anti-CLEC2D antibody sequences, C5397, C5852, C3566, C2901, C4577, C2685, C0694, C0997, C0800, not limited to, and were selected for stable cell line development. 
     Generation of Stable Cell Lines 
     Clinical effectiveness has driven the commercial success of monoclonal antibody (mAb) products. As known to others, mammalian cells are currently the preferred system for large-scale production as the mAbs produced are biochemically similar to human forms. The stable cell line generation process is tedious and time-consuming as clones with high productivity, stable long-term expression and good product quality are rare occurrences. mAb production in mammalian cells can be performed either in transient or stable transfections. As seen in previous section, transient transfections allow relatively fast generation of small amounts of product for use during early stages of drug discovery. However, stably transfected cell lines are more widely used in large scale industrial production. More importantly, stable cell lines used for manufacturing are from a single cell clone in order to obtain high amounts of consistent product. 
     Antibiotic Selection: 
     Antibiotic selection was initiated after transfection at 90% cell viability. Cell suspension was centrifuged at 1400 RPM for 4 mins. Pellet was re-suspended in complete Power CHO2 growth media and concentration of Puromycin Dihydrochloride was adjusted to 2 μg/1×10{circumflex over ( )}6 cells. Antibiotic selection was carried out on every 2nd or 3rd day. Refer table 5 for cell count and viability data. 
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 23 
               
               
                   
               
               
                   
                   
                 Total  
                 Viable 
                   
               
               
                   
                 Viability 
                 cells/ml 
                 cells/ml 
                 Passage 
               
               
                 Experiment 
                 (%) 
                 (×10 6 ) 
                 (×10 6 ) 
                 No 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
               
            
               
                 Transfection R1 
                 95.8 
                 5.42 
                 5.19 
                 35 
               
               
                 Antibiotic selection 1 (AB 1) 
                 90.4 
                 3.73 
                 3.37 
                 36 
               
               
                 Antibiotic selection 2 (AB 2) 
                 78.7 
                 4.3 
                 3.4 
                 37 
               
               
                 Antibiotic selection 3 (AB 3) 
                 82.3 
                 4.4 
                 3.6 
                 38 
               
               
                 Antibiotic selection 4 (AB 4) 
                 80.9 
                 4.8 
                 3.9 
                 39 
               
               
                 Antibiotic selection 5 (AB 5) 
                 81.8 
                 4.0 
                 3.2 
                 40 
               
               
                 Antibiotic selection 6 (AB 6) 
                 77.5 
                 3.9 
                 3.1 
                 41 
               
               
                 Antibiotic selection 7 (AB 7) 
                 76.9 
                 4.2 
                 3.2 
                 42 
               
               
                 Antibiotic selection 8 (AB 8) 
                 84.5 
                 2.0 
                 1.7 
                 43 
               
               
                   
               
            
           
         
       
     
     Repeat Transfection of Stable Pool 
     Cell count was taken using Vi-cell XR (Refer Table 10). Cells were subcultured before the transfection. Two more sequential transfections were performed as mentioned previously. On completion of three rounds of transfection the pool was designated as R3 stable pool. See Table 24. 
     
       
         
           
               
               
               
               
             
               
                 TABLE 24 
               
               
                   
               
               
                 Parameters 
                 Transfection 1 
                 Transfection 2 
                 Transfection 3 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Total volume of transfection  
                 50  
                 ml 
                 21  
                 ml 
                 21  
                 ml 
               
               
                 Cell density 
                 1.25 × 10{circumflex over ( )}6  
                 cells/ml 
                 1 × 10{circumflex over ( )}6  
                 cells/ml 
                 1 × 10{circumflex over ( )}6  
                 cells/ml 
               
               
                 OPTIMEM I 
                 12.5  
                 ml 
                 1 
                 ml 
                 1  
                 ml 
               
               
                 Total DNA 
                 25  
                 μg 
                 5  
                 μg 
                 5  
                 μg 
               
            
           
           
               
               
               
               
            
               
                 HC:LC 
                 1:3 
                 1:3 
                 1:3 
               
               
                 Amount of DNA:Lipofectamine 
                 1:3 
                 1:3 
                 1:3 
               
               
                 Amount of DNA:Plus reagent 
                 1:1 
                 1:1 
                 1:1 
               
               
                   
               
            
           
         
       
     
     Minipool Plating 
     Minipools were generated by serial dilution method. Continuously growing culture of cell line was subcultured at 0.5 million cells/ml in 30 ml complete PowerCHO 2 growth media with 2 mM glutamax, 2 days before plating. Cell count and viability data was collected using Vi-cell XR (refer Table 25). 
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 25 
               
               
                   
               
               
                   
                 Viability 
                 Total cells/ml 
                 Viable cells/ml 
                 Passage 
               
               
                 Experiment 
                 (%) 
                 (×10 6 ) 
                 (×10 6 ) 
                 No 
               
               
                   
               
             
            
               
                 Minipool plating 
                 97.1 
                 2.5 
                 2.4 
                 50 
               
               
                   
               
            
           
         
       
     
     Serial dilution of the cell suspension was carried out in complete Power CHO2 growth media at 1:10 ratio (refer Table 26). 0.52 ml cell suspension was taken from dilution D and added to 25 ml of cloning media. Cells were seeded at a density of 10 cells/well in a 96 well plate in 200 μl volume per well. These mini-pools were maintained at 37° C. temperature in a humidified 5% CO2 incubator. 
     
       
         
           
               
               
               
               
             
               
                   
                 TABLE 26 
               
               
                   
                   
               
               
                   
                   
                 Cell count  
                 Cell count  
               
               
                   
                 Dilution series 
                 (cells/ml) 
                 (cells/ml) 
               
               
                   
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
            
               
                   
                 Culture flask 
                 2400000 
                 1370000 
               
               
                   
                 Dilution A 
                 240000 
                 137000 
               
               
                   
                 Dilution B 
                 24000 
                 13700 
               
               
                   
                 Dilution C 
                 2400 
                 1370 
               
               
                   
                 Dilution D 
                 240 
                 137 
               
               
                   
                   
               
            
           
         
       
     
     Screening of Mini-Pools and Amplification: 
     Total 117 mini-pools were screened by flow cytometry and binding to CHO cell surface expressed antigen was estimated. Minipools were ranked based on cell surface binding wherein the method of sample preparation for flow cytometry was as described above while ˜200 μl of cell culture supernatant expressing anti-CLEC2D antibody proteins and reference positive control, respectively, was used to estimate the membrane bound CLEC2D binding on untransfected CHO cells and C4548 cells ( FIG. 10A ). Minipools identified from flow cytometry screening, as selected through extend of binding as derived from observed fold change in median fluorescence intensity, were amplified from 96 well plate to 24 well plate and maintained at 37° C., humidified condition in a 5% CO2 incubator. These were further amplified from 24 well plate to one well of 6 well plate. After cell were confluent mini-pools were amplified from one well of 6 well plate to a bioreactor tube with 25 ml growth media and maintained at 37° C., humidified condition in a 5% CO2 incubator, 200 rpm. 
     Single Cell Cloning 
     Single cells were generated by serial dilution method. Continuously growing culture of mini-pool was subcultured at 1 million cells/ml in 30 ml complete Power CHO 2 growth media with 2 mM glutamax, 1 day before cloning. Cell count and viability data was collected using Vi-cell XR. Serial dilution of the cell suspension was carried out in complete power CHO2 growth media at 1:10 ratio (refer Table 26). Cells were seeded at a density of 0.5 cells/well in a 96 well plate and maintained at 37° C. temperature in a humidified 5% CO2 static incubator. Cells were aspirated from dilution D and seeded at density of 0.5 cells/200 μl cloning media per well in 96 well plates. The plates were incubated at 37° C., in a 5% CO2 incubator with 75% relative humidity. Plates were scanned by using CloneSelect Imager (Molecular Devices) for monoclonality report generation from day zero to day ten. The individual well images were collected on day 0, day 1, day 2, day 3, day 6, day 8 and day 10. The clonal population was confirmed from the day zero image of entire well and the monoclonality report generated by CloneSelect Imager. Passage number was P(x+0).The Single cell clones were amplified to 24 well plates after cells were confluent. Passage number was P(x+1). 
     Screening of Single Cell Clones and Clone Amplification: 
     Cell surface binding assay was performed to estimate antibody in cell culture supernatant and to rank the clones. Single cell clones showing higher binding on CHO cell surface expressed antigen were amplified from 24 to 6 well after 2 days. Passage number was (x+2). This was followed by amplification in 3 wells of 6 well plate. Passage number was (x+3). The clones were further amplified to tube bioreactors in 20 ml volume, passage number was (x+4). Following amplification RCB vials were prepared for the clones at passage number (x+5). 
     Stable cell culture supernatant was estimated for binding with CLEC2D surface protein on C4548 cells through flow cytometry, wherein the method of sample preparation and experimentation for flow cytometry was as described above while ˜200 μL of cell culture supernatant expressing anti-CLEC2D antibody proteins and reference positive control, respectively, was used to estimate the membrane bound CLEC2D binding on untransfected CHO cells and C4548 cells ( FIG. 10B ). 
     
       
         
           
               
               
               
               
               
             
               
                 TABLE 27 
               
               
                   
               
               
                   
                   
                 Total  
                 Viable 
                   
               
               
                   
                 Viability 
                 cells/ml 
                 cells/ml 
                 Passage 
               
               
                 Experiment 
                 (%) 
                 (×10{circumflex over ( )}6) 
                 (×10{circumflex over ( )}6) 
                 No 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
               
            
               
                 Transfection R1 
                 95.8 
                 5.42 
                 5.19 
                 35 
               
               
                 Antibiotic selection 1 (AB 1) 
                 90.4 
                 3.73 
                 3.37 
                 36 
               
               
                 Antibiotic selection 2 (AB 2) 
                 78.7 
                 4.3 
                 3.4 
                 37 
               
               
                 Antibiotic selection 3 (AB 3) 
                 82.3 
                 4.4 
                 3.6 
                 38 
               
               
                 Antibiotic selection 4 (AB 4) 
                 80.9 
                 4.8 
                 3.9 
                 39 
               
               
                 Antibiotic selection 5 (AB 5) 
                 81.8 
                 4.0 
                 3.2 
                 40 
               
               
                 Antibiotic selection 6 (AB 6) 
                 77.5 
                 3.9 
                 3.1 
                 41 
               
               
                 Antibiotic selection 7 (AB 7) 
                 76.9 
                 4.2 
                 3.2 
                 42 
               
               
                 Antibiotic selection 8 (AB 8) 
                 84.5 
                 2.0 
                 1.7 
                 43 
               
               
                 R1 Stable pool Subculture 
                 96.7 
                 2.6 
                 2.5 
                 44 
               
               
                 R1 Stable pool Subculture 
                 98.3 
                 3.5 
                 3.4 
                 45 
               
               
                 R1 Stable pool Subculture 
                 98.3 
                 3.5 
                 3.4 
                 46 
               
               
                 Transfection R2 
                 98.2 
                 0.79 
                 0.78 
                 47 
               
               
                 Transfection R3 
                 93.0 
                 1.3 
                 1.2 
                 48 
               
               
                 Subculture 
                 93.8 
                 2.3 
                 2.1 
                 49 
               
               
                 Minipool plating 
                 97.1 
                 2.5 
                 2.4 
                 50 
               
               
                 Minipool screening and  
                 NA 
                 NA 
                 NA 
                 51-53 
               
               
                 amplification 
                   
                   
                   
                   
               
               
                 Mini-pool subculture and RCB 
                 NA 
                 NA 
                 NA 
                 54 to 59 
               
               
                 Single cell cloning of Mini-pool 
                 97.50% 
                 1.41 
                 1.37 
                 60 
               
               
                   
               
            
           
         
       
     
     Selection of monoclonal antibody clones expressed and purified from stable cell lines 
     Culture harvest for protein purification: 
     Cells were seeded at a density of approximately 0.3×10 6  cells/ml in 30 ml Complete power CHO2 growth media and cultured for 6 days in 37° C., humidified condition in a 5% CO2 incubator with 120 RPM rotation. 20 ml media top-up was given with complete power CHO2 growth media on 4th day. Cells were harvested by centrifuging the entire cell suspension at 2000 RPM for 10 mins. The supernatant was collected and stored in −20° C. for further purification. Here onwards, all respective stable cell clones containing novel, unique anti-CLEC2D antibody genes will be referred as Cxxxx, wherein xxxx represents four digit numbers (Table 19). Each code represents a specific stable cell line containing specific antibody gene, otherwise mentioned elsewhere. 
     Subsequently, culture supernatants of ˜221 unique and confirmed stable cell clones were subjected to purification through Protein A followed through rational judgement on parameters as exemplified by yet not limited to, purity, titre. In addition, thermal stability estimation via thermal shift assay (TSA) was incorporated as an additional parameter towards selection/screening. 
     Higher melting temperature was considered as a characteristic of more stable protein while proteins with melting temperature less than 65° C. were decided to be not included for further development. TSA experimentation starts with appropriate dilution of protein sample to 0.5 mg/ml concentration in 1×PBS wherein SYPRO-ORANGE fluorescent dye (5000×) was added to the target protein to a final concentration of 5×. Further mixture was centrifuged at 500 RPM for 2 minutes and analyzed by CFX96 Real Time System. Thermal denaturation was carried out by increasing the temperature from 25° C. to 95° C. at a rate of 0.5° C. per minute. Fluorescence intensity was collected at 0.5° C. intervals and analyzed with CFX Maestro software and Tm value was calculated from melt curve. 
     Flow and/imaging: 
     In addition, respective purified anti-CLEC2D proteins were also evaluated for Cell surface binding assay by flow-cytometry and confocal microscopy. The rationale behind inclusion of flow cytometry and confocal microscopy studies was to obtain comprehensive list of anti-CLEC2D clones through a combination ranking matrix. 
     The experimentation including the method of sample preparation for flow cytometry was as described above while ˜1-5 μg of purified anti-CLEC2D antibody proteins and reference positive control, respectively, was used to estimate binding of membrane expressed CLEC2D on untransfected CHO cells and C4548 cells ( FIG. 10C ). 
     The experimentation including the method of sample preparation for imaging acquisition through confocal microscopy was as described above while ˜2 μg of purified anti-CLEC2D antibody proteins, such as, C5848, C8408, C7832, C8800, C5595, C0694, not limited to, and reference positive control, respectively, was used to monitor the membrane bound CLEC2D antigen binding on PC3 cells. As observed through imaging studies for Anti-CLEC2D purified from stable cell clones, not limited to, C5848, C8408, C8800, C5595, C7832, exhibits uniform yet differential CLEC2D antigen binding on the surface of PC3 cells ( FIG. 10D ). 
     In order to assess/understand the stability of anti-CLEC2D antibody genes in stable cell clones, quantitative measurements through RT PCR was adopted wherein amplification of stably integrated anti-CLEC2D antibody genes into CHO cell genome would be monitored and estimated. CHO cell pellets were obtained from every passage as part of a continuous subculture of respective clones for 60 generations corresponding to P01 as first passage while P18 represents final 60 th  generation. Herein, genomic DNA (gDNA) were isolated from cell pellets using the DNeasy® Blood &amp; Tissue kit (QIAGEN GmbH, Hilden, Germany) according to the manufacturer&#39;s protocol (protocol for cultured cells with proteinase K treatment). Concentration and purity of gDNA preparations were analyzed spectrophotometrically using Eppendorf BioPhotometer® D30 (Eppendorf AG, Germany). The isolated gDNA were diluted to a concentration of 100 ng/μL and passed through BD Ultra-Fine™ Needle Insulin Syringes (Becton, Dickinson and Company, NJ, USA) for qPCR. To quantify the Ct values qPCR was performed on a CFX96TMReal-Time system with 96-well, thin wall Hard-Shell PCR plates and Microseal® ‘B’ seal film sealer (all from Bio-Rad, Hercules, Calif., USA) using the designed primers. Each qPCR run was performed with each sample in triplicates. GAPDH used as relative control and no template controls (NTC) were included in each qPCR run. Each reaction mix contained 12.5 μL of SYBR™ Green PCR Master Mix (appliedbiosystems by Thermo Fisher Scientific, Life technologies, Woolston Warrington, UK), 10 pmol of each primer (synthesised at Eurofins, Bangalore, India) and 100 ng lysed gDNA adjusted with Water, HPLC (HiMedia Laboratories, Mumbai, India) to a final volume of 25 μL. The qPCR run was performed as a 2-step protocol with an initial denaturation step at 95° C. for 10 min followed by 40 cycles of denaturation at 95° C. for 15 sec and annealing at 60° C. for 60 sec. Raw data were processed by the Bio-Rad CFX Manager™ software application version 3.1.1517.0823 (BioRad) using the settings baseline subtraction, to obtain the Cq (Cycle Quantification) values. 
     The described quantitative approach was employed for all clones, as exemplified by, for C5511, C4608. The data obtained from the study has been depicted in  FIG. 10E . indicating non significant variation of &lt;5% in Ct values for respective antibody chains across all passage numbers confirming the stable integration of anti-CLEC2D antibody genes into CHO cell genome and sustained for at least 60 generations. 
     Considering the combinatorial matrix, the number of stable cell line was selected to 11 clones, as exemplified by, C4608, C7720, C5093, C3452, C9136, C3641, C5372, C6481, C5511, C6726, C5392. Here onwards, understanding towards large scale production aspect and functionality feature, such as, anti-CLEC2D antibody driven cytotoxicity, was incorporated towards selection of final clones for further development. 
     For the process of clone selection, it was essential to have a method which is robust, repeatable and produces protein of consistent quality. Therefore, before clone screening was initiated, a platform process was developed to ensure efficient clone screening. A fed batch process was developed using ActiPro as basal media and cell boost 7a and cell boost 7b as the feeding. The interval and quantity of feeding was experimentally optimized and the optimized process was repeated to establish robustness. The fed process was further extended to clone screening to isolate the top performing clones. After the top performing clones were isolated, the clones were verified by culturing cells in a 10 L bioreactor using the optimized fed batch process. This step was carried out to ensure manufacturability of clones selected when transferred to a larger scale. 
     ActiPro media was chosen as the basal media for development of platform process, on the basis of historical data of comparison with different basal media. ActiPro was supplemented with 4 mM glutamine to ensure metabolic requirements of cell are met. 
     Multiple monoclonal cell lines were evaluated in order to understand, rank and select the better performers. Based on the results obtained on Viable Cell Density, Viability, Titer, C5511, C4608, C3452, C5392, C6481 were assessed to be best performers in terms of all the performance parameters. 
     Surface Antigen Expression on Various Prostate Cancer Cell Lines: PC3 
     Tumor cells expressing CLEC2D antigen were harvested by trypsinization. Cell count was taken by Vi-cell XR automated cell counter. Cells were centrifuged at 1400-1500 rpm for 4-5 minutes. The pellet was re-suspended in 1 ml DPBS. 50,000 cells were aliquoted in each well of a 96 well plate. 1 μg of test samples, as exemplified by C5511, control were added to each well and incubated for 30-60 minutes at room temperature (25° C.). The plate was centrifuged at 1400-1500 rpm for 4-5 minutes, the supernatant was aspirated and cells were washed with 0.1% BSA in DPBS. 2.5 ml of 2% BSA was diluted to 50 ml with DPBS. Goat anti human IgG FITC conjugate was used as secondary antibody. 1:100 dilution of secondary antibody was prepared in DPBS and 100 μl was added to each well. Goat anti human IgG FITC conjugate was used as control at dilution of 1:100. The plate was incubated for 30 minutes at room temperature (25° C.) in dark. The cells were washed with 0.1% BSA and re-suspended in 100 μl of 1% BSA. Samples were analyzed by flow-cytometry. 
     Binding of test samples were estimated and used for calculation of specific binding on tumor cell surface using following formula: 
     
       
         
           
             
               Fold 
                
               
                   
               
                
               change 
                
               
                   
               
                
               in 
                
               
                   
               
                
               M 
                
               
                   
               
                
               F 
                
               
                   
               
                
               I 
             
             = 
             
               
                 
                   
                     
                       Median 
                        
                       
                           
                       
                        
                       FITC 
                        
                       
                         - 
                       
                        
                       A 
                        
                       
                           
                       
                        
                       of 
                        
                       
                           
                       
                        
                       test 
                        
                       
                           
                       
                        
                       sample 
                     
                   
                 
               
               
                 
                   
                     
                       Median 
                        
                       
                           
                       
                        
                       FITC 
                        
                       
                         - 
                       
                        
                       A 
                        
                       
                           
                       
                        
                       of 
                        
                       
                           
                       
                        
                       control 
                     
                   
                 
               
             
           
         
       
     
     Fold change in MFI of PC3 surface binding, as observed from flow cytometry experiments, as exemplified while not limited to, C5511, C4608, C6481, C2438, C3452, C0949antibody, was found to be increased by more than 2 folds when compared against control ( FIG. 11A ). 
     Further, surface binding was with various unique anti-CLEC2D antibody stable clones on the surface of PC3 through binding of antibody on the surface of PC3 cells through confocal microscopy, as described in Example 5, Section: Cell surface binding assay: through Flow Cytometry and Confocal Microscopy. As depicted in  FIG. 11A , the binding of purified novel anti-CLEC2D on the surface of PC3 was observed with uniform distribution of CLEC2D antigen through novel antibody on PC3 cells. 
     Cytotoxicity Assay: Through Flow Cytometry and Imaging Methods 
     To assess the functional activity of anti-CLEC2D, cytotoxicity assay was performed employing both flow cytometry and confocal microscopy methods, with isolated PBMCs and incubated with target cell and anti-CLEC2D. Prior to this, optimization on mAb concentration and ideal T:E ratio was carried out. 
     Effector cells, PBMCs from healthy donors were isolated as per previous protocol (Jewett A, J Immunol 1996). Briefly, peripheral blood lymphocytes were obtained after Histopaque-1077 (Sigma) centrifugation. 1:2 diluted blood was layered on 15 mL Histopaque. All the reagents were maintained in room temperature. Tube containing histopaque and blood was centrifuged at 400 g for 30 minutes at room temperature with zero acceleration and brake. After centrifugation, upper layer was carefully aspirated to within 0.5 cm of the opaque interface containing mononuclear cells and the upper layer was discarded. Opaque interface was carefully transferred into a centrifuge tube. Cells were washed twice by adding 10-15 mL of 1×PBS at 250 g for 10 minutes. Pellet was resuspended in 2 mL of PBS and PBMCs count was done. Total 10 million PBMC was obtained from 10 mL of blood. Quality check of PBMC was done based on flow cytometry with CD45+ population 99%. NK cells were isolated via negative selection using NK isolation kit (Stem cells technologies, Vancouver, BC, Canada). The purity of NK cells was found to be &gt;90% based on flow cytometry CD56+ population. 
     Target prostate cancer cell line, PC3 cells were labelled with Efluor as per the manufacturer&#39;s protocol and were seeded at a density of 0.04×10 6  in 20% DMEM in 24 well plates. After 24 hours, freshly isolated PBMCs were added in T:E of 1:5. Novel monoclonal anti-CLEC2D antibodies C5511, C6481, C5392, C3452 and C4608, not limited to, were added at ˜200 μg/ml in the assay reaction of 0.5 ml and incubated for 14 hours. Supernatant was collected from 24 well plate and adherent cells were trypsinized and collected in 1.5 ml tubes. Reaction mixture was incubated with sytox green (15 nM) for 20 min and fluorescence was detected in flow cytometer. Percent specific cell death was determined by subtracting the percent cell death of control from the test samples. 
     Cytotoxicity was analysed by dual target cell staining by flow cytometry.  FIG. 11B  shows cytotoxicity of the 3 novel anti-CLEC2D monoclonal antibodies, C5511(˜41%), C4608(˜32%) and C6481(˜37%) was observed compared with the control wherein percent cell death was measured from PBMC, isolated from donor 1, and target cell, incubated together at 1:5 ration without treatment. Following similar conditions, C5392 and C3452 clones were tested on donor 2 wherein cytotoxicity was found to be be ˜14% and ˜28%, respectively ( FIG. 11B ). More than 80% cytotoxicity of target cells was observed when anti-CLEC2D concentration was increased from 50 μg/ml to 200 μg/ml ( FIG. 11C ) and significant increase in tumour cell killing was also monitored when T:E ratio was increased from 1:5 to 1:10 ( FIG. 11D ). 
     For confocal microscopy experiments, PC3 cells were grown on 8-well slides (eppendorf) in complete media (20% FBS+DMEM-F12+1× Pen/Strep+1 mM sodium Pyruvate) to 70-80% of confluence. Freshly isolated PBMC cells were left overnight in culture media (RPMI1640 with 10% FBS) prior to be used in cytotoxicity as resting PBMC cells. PC3 cells were stained with cell tracker dye (100 nM) and PBMC cells were stained with cell proliferation dye EF670 (10 μM) separately. Different concentrations of novel antibodys along with stained PC3 and PBMC cells incubated for 6-7 hrs then images were acquired using Olympus FV3000-4 laser scanning confocal microscope with a 60× magnification, 1.35-NA objective. Laser light used for death dye sytox blue (at 5 μM), λex 405 nm and λem 450-500 nm; for cell tracker green, λex 488 nm and λem 510-530 nm; for cell proliferation dye EF670 λex 640 nm and λem 650-750 nm. Images were analyzed with Fiji ImageJ software. 
     In order to identify the optimal concentration of novel mAb for the cytotoxicity assay, target to effector cells ratio (1:5) and 3 different concentrations (i.e., 10 μg/ml, 20 μg/ml and 50 μg/ml) of novel anti-CLEC2D antibody (C6726) was used and incubated for 6-7 hrs in complete media. Cell death was monitored by disappearance of green fluorescence and appearance of violet fluorescence on PC3 cells. Maximum cytotoxicity observed at 50 μg/ml ( FIG. 11E ). Further end point cell death assay was continued using a concentration of 50 μg/ml for the same incubation timing for other antibody clones, not limited to, C6726, C4608, C5848, C5511, C6481, clones tested ( FIG. 11F ) indicating that the target cell death is observed in the presence of novel antibodies while no cell death was monitored when targets cells were not treated with novel antibodies. 
     Based on available data as described above, C4608, C5511, C6481, C5392 and C3452 clones were selected for final in vivo mouse efficacy experimentation. 
     During the development of therapeutic monoclonal antibodies (mAbs), a strategy for early identification of candidate antibodies with the greatest likelihood of success in the clinic is needed to avoid costly late-stage failures related to inadequate exposure, toxicity or lack of efficacy. Early screening and optimization of mAbs focus on characteristics such as affinity, potency and stability for selection of lead constructs, while confirmation on in vivo efficacy are typically required, although, characterized later in development and on a small number of lead mAb constructs. Herein, confirmed anti-CLEC2D clones, C4608, C5511, C6481, C5392 and C3452 were subjected to evaluate for in vivo efficacy against prostate cancer xenograft. 
     Example 6: Deciphering the Mechanism of Action of Novel Anti-CLEC2D Antibody Molecule 
     Immune checkpoints consist of inhibitory and stimulatory pathways that maintain self-tolerance and assist with immune response. In cancer, immune checkpoint pathways are often activated to inhibit the nascent anti-tumor immune response. Immune checkpoint therapies act by blocking or stimulating these pathways and enhance the body&#39;s immunological activity against tumors. Under normal circumstances, immune checkpoints allow the immune system to respond against infection and malignancy while protecting tissues from any harm that may derive from this action. However, the expression of some of these immune-checkpoint proteins by malignant cells dysregulates the antitumor immunity and favours the growth and expansion of cancer cells. Understanding the mechanism of action for immunotherapy, especially though monoclonal antibody based therapies, though multiple approaches would further reinvigorates on specific ways whether alone or in combination, that works in favour of tumour cell killing. 
     In present disclosure, mechanism of anti-CLEC2D antibody, as can be understood from in vitro experimentation, usually consists of events occurred at molecular interaction level, such as CLEC2D target dependence, interaction between CLEC2D/CD161, at cellular network level such as involvement of various effector cells, eg., natural killer (NK) cell, T cells on killing of tumour cells in presence or absence of anti-CLEC2D antibody, or specific mechanism that are driven by isotype of anti-CLEC2D antibody such as ADCC, CDC, ADCP and/or in combination, tumour cell death induced by elevation of cytokine/chemokine levels or various activating/inhibitory receptor&#39;s expression or in combination, and from in vivo experimentation, wherein, tumour regression occurred through lymphocyte infiltration. 
     Moreover, as the functions and target molecules of antibodies are more diverse, it becomes increasingly necessary to understand how the target molecule functions biologically and what will be the biological response to the modified functions induced by the antibody. Having mentioned this, understanding on mechanism of action will have immense emphasis on prostate cancer treatment, specifically on castration resistant prostate cancer, and will pave avenues for whole spectrum of multiple disease indications with novel immunotherapy strategies. Having mentioned this, a thorough employment of rational approach/stratification will ensure consistent incorporation of better-understood immunology in to cancer therapy and will dramatically impact on the development of overall therapeutic landscape. 
     The specific cell type involved in cytotoxicity was investigated through flow cytometry and confocal microscopy, wherein, in microscopy based approaches having both end point assay and live cell imaging methods. 
     NK Cell Mediated Cytotoxicity PC3 cells were labelled with Efluor as per the manufacturer&#39;s protocol and were seeded at a density of 0.04×10 6  in 20% DMEM in 24 well plates. After 24 hours, freshly isolated NK cell was added in T:E of 1:1. Novel monoclonal anti-CLEC2D antibody C5511 and C6481 were added at 100 μg/ml in the assay reaction of 0.5 ml and incubated for 14 hours. Supernatant was collected from 24 well plate and adherent cells were trypsinized and collected in 1.5 ml tubes. Reaction mixture was incubated with Sytox green (15 nM) for 20 min and fluorescence was detected in flow cytometer. Percent specific cell death was determined by subtracting the percent cell death of control from the test samples. NK cell-mediated cytotoxicity (NKCC) was determined by using freshly isolated NK cells co-incubated with prelabelled target tumor cell line and anti-CLEC2D for 14 hours. Assay samples were incubated with dead cell dye sytox green and fluorescence was measured by flow cytometry. As estimated, Anti-CLEC2D antibody exhibited more than 80% cell death in the cytotoxicity assay ( FIG. 12A ). 
     Confocal microscopy based approach was employed further to understand the impact of NK cell mediated cytotoxicity through both fixed cell imaging and live cell imaging. 
     PC3 cells were grown on 8-well slides (eppendorf) in complete media (20% FBS+DMEM-F12+1× Pen/Strep+1 mM sodium Pyruvate) to 70-80% confluence. NK cells were isolated as described above. Freshly isolated NK cells were left overnight in in 10% RPMI media overnight prior to be used in cytotoxicity as resting NK cells. PC3 cells were stained with cell tracker dye and NK cells were stained with cell proliferation dye EF670 separately. Different ratio of NK: target cells (1:0.5, 1:5, 1:10) were used along with 50 μg/ml of novel antibodies, not limited to, C5511, C4608, C6481, and were incubated for 6-7 hrs before image acquisition using Olympus FV3000-4 laser scanning confocal microscope with a 60× magnification, 1.35-NA objective. Laser light used for death dye sytox blue, λex 405 nm and λem 450-500 nm; for cell tracker green, λex 488 nm and λem 510-530 nm; for cell proliferation dye EF670 λex 640 nm and λem 650-750 nm. Images were analyzed with Fiji ImageJ software. 
     To explore the role of NK cells on cytotoxicity, we have incubated PC3 with different ratio of NK cells along with the fixed concentration of novel antibodies for 6 to 7 hrs. We have observed an increase in cell death with increasing in ratio of E:T for all antibodies tested (C5511, C4608, C6481) wherein T:E ratio of 1:10 exhibited highest cell death as indicated in  FIGS. 12B, 12C, and 12D ). 
     T Cell Mediated Cytotoxicity 
     PC3 cells were labelled with Efluor as per the manufacturer&#39;s protocol and were seeded at a density of 0.04×10 6  in 20% DMEM in 24 well plates. Freshly isolated T cell was used in the cytotoxicity assay at T:E of 1:3 and antibody concentration of 100 ug/ml. Novel monoclonal anti-CLEC2D antibody C5511 and C6481 were added at 100 ug/ml in the assay reaction of 0.5 ml and incubated for 14 hours. Supernatant was collected from 24 well plate and adherent cells were trypsinized and collected in 1.5 ml tubes. Reaction mixture was incubated with sytox green (15 nM) for 20 min and fluorescence was detected in flow cytometer. Percent specific cell death was determined by subtracting the percent cell death of control from the test samples. 
       FIG. 13  depicts T cell mediated killing as observed against PC3 cells wherein clone C5511 &amp; C6481was incubated at a concentration of 100 μg/ml eliciting tumor cells cytotoxicity when compared with control having basal level of 6% dead cell. In experimental condition where T:E of 1:3 was used, upto 55% T cell mediated cytotoxicity was observed ( FIG. 13 ). 
     To further define the process of cytotoxicity live-cell microscopy experiments were performed to track the target cell killing through effector cells for both PBMC and NK cells. For live cell imaging experimentation, PC3 cells were grown on 8-well slides (eppendorf) in complete media ((20% FBS+DMEM-F12+1× Pen/Strep+1 mM sodium Pyruvate)) to 70-80% confluence. PC3 cells were stained with cell tracker dye and PBMC/NK cells were stained with cell proliferation dye EF670 separately. 200 m/ml of novel antibodies along with stained PC3 and PBMC/NK cells. Target to effector ratio for both PBMC and NK cells were, 1:5 and 1:1, respectively. Cells were kept in a humidifier maintained at 37° C. and 5% CO2 during imaging. Live cell imaging was performed on the Zeiss LSM800 confocal microscope with a 63× magnification, 1.4-NA objective and images were captured at 8 min intervals for up to 20 hrs by using appropriate wavelengths (For sytox blue, λex 405 nm and λem 450-500 nm; for cell tracker green, λex 488 nm and λem 510-530 nm; for cell proliferation dye EF670 λex 630 nm and λem 650-750 nm. Images were analyzed with Zen lite Imaging software. 
     To further define the process of cytotoxicity, live-cell microscopy was performed to track the target cell killing through effector cells either PBMC or NK cells. 
     The purpose of live cell imaging was to understand and follow the anti-CLEC2D mediated tumour cell killing process in the presence of effector cells, such as PBMC or NK cell, in time dependent manner, under controlled experimental condition. Results obtained from live cell imaging prompted the fact that in the presence of isotype control, PBMC or NK cell made less direct contact with the PC3 target cells resulting in minor percentage of target cell death. On the contrary, addition of anti-CLEC2D (C5511) antibodies, on PBMC or NK cells and target cells causing an increase in extend of direct contacts between both PBMC or NK cells and PC3 target cells, resulting in significant target cell death. Interestingly, PC3 target cell killing mediated by anti-CLEC2D (C5511) antibody in presence of NK cells elicited more efficient clearance of tumor cells wherein most of the tumor cells lysis occurred within 10 hrs of incubation, while observed tumor cell death in presence of PBMC was found to be significantly lower within the said time point. This indicates that effective elimination of PC3 tumor cells via anti-CLEC2D antibody is predominantly NK cell mediated. 
     Molecular Interaction Between Anti-CLEC2D Antibody and CLEC2D Antigen: Through Epitope Mapping 
     In Silico Studies 
     The following protocol was developed to identify the binding site formed by the CLEC2D-Antibody complexes. Briefly the method involves using protein structures of both the antibody and CLEC2D in shape-complementarity based docking to generate CLEC2D-antibody conformations, followed by analysis of the conformation to shortlist mutations to verify the binding sites. (Germain et al, 2011, Rozbesky et al, 2015). 
     One of the central assumptions of this protocol is that the potential binding site should be more accommodating of a binding partner, i.e., a groove or channel—where an appropriate binding partner may be able to settle, somewhat illustrated by the lock-and-key model of enzymes and substrates, a specific lock (or binding site) would be receptive to a specific key (or binding partner) based on their structural compatibility. This concept was expanded upon to identify the binding site, as following shape-based docking, the largest concentrations of generated conformations were considered to be the possible binding sites. 
     The conformations were then clustered together on the basis of interacting pairs of residues, conformations that could not be incorporated into clusters were discarded after which the remaining conformations were energy minimized and screened for viability. For conformations found to be viable their interacting residue pairs were more closely scrutinized and mutations were suggested to test the association. 
     Killer cell lectin-like receptor subfamily B member 1 (NKR-P1) is an inhibitory receptor the regulates NK cell-mediated cytotoxicity. C-type lectin domain family 2 member D (CLEC2D) is a ligand of NKR-P1, the CLEC2D/CD161 interaction inhibits NK cell-mediated cytotoxicity, blocking the CLEC2D-NKR-P1 complex can enhance primary NK cell activity. 
     All unique anti-CLEC2D antibodies derived from novel library was found to prevent the CLEC2D-NKR-P1 association by binding with CLEC2D, however the exact location and nature of this inhibition was unknown. The following protocol was conceived to identify the likelihood of binding site through the use of modelling, docking and site-directed mutagenesis. 
     The procedure starts with identifying key interaction residues on CLEC2D wherein, the CLEC2D-antibody complex interactions can be understood by taking a closer look at the CLEC2D-NKR-P1(CD161) complex and was done by studying the crystal structure of the complex, deposited in the PDB as 5MGT ( FIG. 15A ). 
     The 5MGT crystal structure describes the association between the CLEC2D and NKR-P1 complex. The residues involved in the association are of interest. If the inhibition mode of the antibody-CLEC2D complex is of a steric variety, the residues involved in both interactions, and their immediate neighbors, would likely overlap. Residues involved from the CLEC2D chains, henceforth called antigen interacting residues were identified by examining the 5MGT structure in Chimera ( FIG. 15B ) (Pettersen et al, 2004). Essentially all residues within contact distance (up to 6 Å) between the chains of CLEC2D and NKR-P1(CD161) were identified (See Table 28). 
     
       
         
           
               
             
               
                 TABLE 28 
               
             
            
               
                   
               
               
                 A list of the residues in CLEC2D Chains within  
               
               
                 contact distances of NKR-P1(CD161). 
               
            
           
           
               
               
               
               
               
               
               
               
            
               
                 Res No. &amp; 
                   
                   
                   
                 Res No. &amp; 
                   
                   
                   
               
               
                 Type 
                 6 Å 
                 5 Å 
                 4 Å 
                 Type 
                 6 Å 
                 5 Å 
                 4 Å 
               
               
                   
               
               
                  91 ASP 
                 ✓ 
                 ✓ 
                 X 
                 161 GLY 
                 ✓ 
                 ✓ 
                 X 
               
               
                  92 ASP 
                 ✓ 
                 X 
                 X 
                 162 GLU 
                 ✓ 
                 ✓ 
                 ✓ 
               
               
                  93 THR 
                 ✓ 
                 ✓ 
                 X 
                   
                   
                   
                   
               
               
                  95 ASN 
                 ✓ 
                 X 
                 X 
                 165 TYR 
                 ✓ 
                 ✓ 
                 ✓ 
               
               
                   
                   
                   
                   
                 167 ASN 
                 ✓ 
                 ✓ 
                 ✓ 
               
               
                 124 ARG 
                 ✓ 
                 X 
                 X 
                 168 ASP 
                 ✓ 
                 ✓ 
                 X 
               
               
                 126 LYS 
                 ✓ 
                 ✓ 
                 X 
                 169 LYS 
                 ✓ 
                 ✓ 
                 ✓ 
               
               
                 127 GLY 
                 ✓ 
                 ✓ 
                 X 
                   
                   
                   
                   
               
               
                 128 PRO 
                 ✓ 
                 ✓ 
                 ✓ 
                 172 SER 
                 ✓ 
                 ✓ 
                 X 
               
               
                 129 SER 
                 ✓ 
                 ✓ 
                 ✓ 
                 173 SER 
                 ✓ 
                 ✓ 
                 ✓ 
               
               
                 130 ASP 
                 ✓ 
                 ✓ 
                 ✓ 
                 174 ALA 
                 ✓ 
                 ✓ 
                 ✓ 
               
               
                 131 HIS 
                 ✓ 
                 X 
                 X 
                 175 ARG 
                 ✓ 
                 ✓ 
                 ✓ 
               
               
                   
                   
                   
                   
                 177 TYR 
                 ✓ 
                 ✓ 
                 ✓ 
               
               
                 139 GLN 
                 ✓ 
                 ✓ 
                 ✓ 
                 178 THR 
                 ✓ 
                 ✓ 
                 ✓ 
               
               
                   
                   
                   
                   
                 179 GLU 
                 ✓ 
                 ✓ 
                 ✓ 
               
               
                 158 LEU 
                 ✓ 
                 ✓ 
                 X 
                 180 ARG 
                 ✓ 
                 ✓ 
                 ✓ 
               
               
                 159 GLY 
                 ✓ 
                 ✓ 
                 X 
                 181 LYS 
                 ✓ 
                 ✓ 
                 ✓ 
               
               
                 160 ALA 
                 ✓ 
                 ✓ 
                 ✓ 
               
               
                   
               
            
           
         
       
     
     These antigen-interacting residues were known to play crucial roles in the NKR-P1(CD161)-CLEC2D complex and would therefore be considered as ‘significant’ residues in the following conformation analysis. 
     Building Antibody Structures 
     Models of the fourteen antibodies were generated through the use of homology modelling program MODELLER. The models generated were limited to the variable regions of the antibody, as that is the main area of interest. The PDB was parsed for structures of complete variable regions of antibodies. Each of the unique antibody variable region sequences were aligned against the available structures&#39; sequences and the best match for each antibody sequence, was used as the template from which the antibody model was built. Multiple models were generated for each sequence and the most energy efficient structure was selected as the main model for the antibody ( FIG. 15C ). 
     Antibodies are very well conserved outside their hypervariable Complementarity Determining Regions (CDR) loops, and of the six CDR on the two chains of the antibody, three on each of the heavy and light chains, the CDR3 loop on the heavy chain is known to be the largest and most influential in the establishment of interactions, and this region along with the light chain CDR3, were run through several rounds of MODELLER&#39;s Loop Refinement to generate the most energy efficient structures, with respect to the CDR loops. Once again multiple variants of the main model were generated and the most energy efficient one was taken forward as the refined antibody model. 
     Docking the Antibody on the CLEC2D 
     The CLEC2D model was acquired from the PDB, deposited as 4QKI a dimer of CLEC2D chains. As the precise location of the interaction is not known, Molecular Docking was used to generate structures of the complex to explore the possible interaction modes. The program used was PatchDock, a shape complementarity docking program which permutes all possible interaction modes based on structural feasibility. (Schneidman-Duhovny et al, 2005) 
     Docking was carried out between the refined Antibody Variable region structures and the antigen CLEC2D (PDB: 4QKI), using PatchDock&#39;s High Accuracy Mode at a cluster distance of 4 Å (preventing conformations within 4 Å of existing conformations from being generated). Constraints were only provided for the antigen structure, wherein both CDR3 loops from the light and heavy chains were specified. 
     PatchDock generated several docking conformations against each of the provided antibodies. (See Table 29). 
     
       
         
           
               
             
               
                 TABLE 29 
               
             
            
               
                   
               
               
                 The number of 
               
               
                 output structures for 
               
               
                 each Docking of 
               
               
                 the unique anti- 
               
               
                 CLEC2D 
               
               
                 antibody refined 
               
               
                 structures against  
               
               
                 CLEC2D. 
               
            
           
           
               
               
               
            
               
                   
                 Refined 
                 Conformations 
               
               
                   
                 Structure 
                 Generated 
               
               
                   
                   
               
            
           
           
               
               
               
            
               
                   
                 1 
                 6424 
               
               
                   
                 2 
                 17370 
               
               
                   
                 3 
                 7338 
               
               
                   
                 4 
                 9245 
               
               
                   
                 5 
                 17976 
               
               
                   
                 6 
                 17170 
               
               
                   
                 7 
                 20617 
               
               
                   
                 8 
                 5750 
               
               
                   
                 9 
                 18198 
               
               
                   
                 10 
                 7604 
               
               
                   
                 11 
                 10267 
               
               
                   
                 12 
                 12699 
               
               
                   
                 13 
                 15655 
               
               
                   
                 14 
                 6219 
               
               
                   
                   
               
            
           
         
       
     
     Analysing Conformations 
     Following the generation of the docked conformations, their interacting residues were analysed. 
     In house scripts were used to query the complex structure and identify all residue pairs involving participants from different chains, at a maximum distance of 4 Å from one another. These residue pairs were compiled into lists, Table 30 and 31 show such a few lines from such a list, which were then used to cluster the conformations. 

 
     Clustering Conformations and Assessing Viability 
     Conformations were clustered on the basis of overlapping contacts, conformations were clustered together if at least 75% of the residue pairs were in common. Conformations that were not incorporated into a cluster were discarded. 
     Of the remaining structures, energy minimization was carried out on all the complexes before the next filtration step where the Protein Interaction Z Score Assessment (PIZSA) tool was used to filter out non-binder conformations. PIZSA took in the protein complexes and identified all the likely residue interactions on the basis of a distance threshold applied to the residues&#39; atoms. Following identification it evaluated every contact pair and scored the constituent associations, building up a cumulative score which was ultimately used to determine if the associations it has identified would lead to stable association, if the complex is viable, or not. (Roy et al, 2019) (This viability is based on the composition and combinations of the identified contact pairs.) Conformations identified as viable were the only ones retained. (See Table 32). 
     
       
         
           
               
             
               
                 TABLE 32 
               
             
            
               
                   
               
               
                 The Total numbers and membership data of  
               
               
                 clusters identified when clustering was carried  
               
               
                 out for 75% identify of interactions. The final  
               
               
                 column lists the number of conformations that  
               
               
                 are recognised as PIZSA as being viable. 
               
            
           
           
               
               
               
               
            
               
                   
                 Total  
                 Total  
                 Viable 
               
               
                 Antibody 
                 Clusters 
                 Conformations 
                 Conformations 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                 C2901 
                 13 
                 100 
                 69 
               
               
                 C4608 
                 19 
                 138 
                 117 
               
               
                 C3452 
                 6 
                 30 
                 9 
               
               
                 C5511 
                 7 
                 44 
                 39 
               
               
                 C0694 
                 4 
                 29 
                 9 
               
               
                 C0997 
                 6 
                 44 
                 37 
               
               
                 C5397 
                 3 
                 21 
                 21 
               
               
                 C5392 
                 7 
                 47 
                 36 
               
               
                 C0949 
                 6 
                 43 
                 42 
               
               
                   
               
            
           
         
       
     
     These reduced clusters were composed of several tightly grouped structures, all of which formed overlapping associations with the CLEC2D chain. 
     These cluster formations were taken as likely binding site positions and the validation of each site needed to be carried out ( FIGS. 15D, 15E, 15F, and 15G ). 
     Mutation Analysis 
     Following the short-listing of a smaller number of viable structures to explore, mutation analysis was carried out. PIZSA also had a feature whereby it takes identified contact pair and substitutes each participant residue with the other 19 natural amino acids and determined the impact on the overall score of the structure for that substitution. The impact value would be indicative of the loss of stability the complex would experience if a specific residue was swapped out for another. Residues that were important for the complex, which form strong associations would have high impact values, as mutating those positions could weaken or destabilise the complex. This information was used to identify which residue pairs mutations would be the most destabilizing to the overall complex. As the conformations were already clustered, an entire cluster could be evaluated by around identifying three to four high impact residue-pairs that were prevalent in all members of the clusters, for mutation. Herein significant considerations were made based on following parameters, such as, Same Cluster Count indicating the total number of times a specific residue was observed in an interaction within same cluster on the same antibody; Same_Cluster_Proportionate indicating proportionate number of times a specific residue was observed in an interaction within same cluster on the same antibody; Same antibody in Other Cluster occurrence count meaning the total number of times a specific residue was observed in an interaction among all clusters on the same antibody that can be seen multiple times in the same cluster; Same antibody Other Cluster count describes the total number of structures in which a specific residue was observed in an interaction among all clusters on the same antibody capturing multiple instances in the same cluster however only counted once; Other antibody Other Cluster occurrence count describes as the total number of times a specific residue was observed in an interaction among all clusters on the other antibodies; Other antibody other Cluster count indicating the total number of structures in which a specific residue was observed in an interaction among all clusters on other antibodies (multiple instances in the same cluster only counted once). Taking together, this approach in turn provided the epitope patch on CLEC2D antigen against respective anti-CLEC2D antibody. The similar method was justifyably adopted for all anti-CLEC2D antibodies as well. 
     
       
         
           
               
             
               
                 TABLE 33 
               
             
            
               
                   
               
               
                 summarizes on significant residues on CLEC2D antigen contacting C4608 anti-CLEC2D antibody 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                   
                   
                   
                   
                   
                   
                 Same Ab 
                 Same 
                 Other Ab 
                 Other 
                   
               
               
                   
                   
                   
                   
                   
                 Same 
                 Other 
                 Ab 
                 Other 
                 Ab 
                   
               
               
                   
                   
                   
                   
                 Same 
                 Cluster 
                 Cluster 
                 Other 
                 Cluster 
                 Other 
                   
               
               
                 Clone 
                 Cluster 
                   
                   
                 Cluster 
                 Propor- 
                 occurrence 
                 Cluster 
                 occurrence 
                 Cluster 
                 CD161 
               
               
                 No. 
                 No. 
                 Residue 
                 Position 
                 Count 
                 tionate 
                 count 
                 count 
                 count 
                 count 
                 overlap 
               
               
                   
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
            
               
                 C4608 
                 G00001 
                 ARG 
                 101 
                 10 
                 100 
                 26 
                 4 
                 100 
                 22 
                 No 
               
               
                   
                 G00001 
                 SER 
                 105 
                 6 
                 100 
                 15 
                 4 
                 36 
                 11 
                 No 
               
               
                   
                 G00004 
                 ASP 
                 104 
                 8 
                 100 
                 7 
                 3 
                 26 
                 8 
                 No 
               
               
                   
                 G00007 
                 PHE 
                 102 
                 3 
                 100 
                 13 
                 4 
                 27 
                 12 
                 No 
               
               
                   
                 G00007 
                 SER 
                 98 
                 1 
                 100 
                 10 
                 5 
                 37 
                 19 
                 No 
               
               
                   
                 G00007 
                 SER 
                 105 
                 6 
                 100 
                 15 
                 4 
                 36 
                 11 
                 No 
               
               
                   
                 G00008 
                 TYR 
                 177 
                 7 
                 100 
                 10 
                 1 
                 145 
                 25 
                 Yes 
               
               
                   
                 G00008 
                 GLU 
                 179 
                 5 
                 100 
                 14 
                 3 
                 129 
                 20 
                 Yes 
               
               
                   
                 G00009 
                 GLU 
                 138 
                 5 
                 100 
                 7 
                 4 
                 66 
                 20 
                 No 
               
               
                   
                 G00009 
                 GLN 
                 141 
                 10 
                 100 
                 21 
                 5 
                 82 
                 17 
                 No 
               
               
                   
                 G00010 
                 PHE 
                 102 
                 7 
                 100 
                 0 
                 0 
                 14 
                 8 
                 No 
               
               
                   
                 G00010 
                 ARG 
                 101 
                 13 
                 100 
                 2 
                 2 
                 82 
                 17 
                 No 
               
               
                   
                 G00011 
                 THR 
                 152 
                 3 
                 100 
                 10 
                 2 
                 67 
                 21 
                 No 
               
               
                   
                 G00011 
                 ARG 
                 153 
                 12 
                 100 
                 12 
                 2 
                 159 
                 25 
                 No 
               
               
                   
                 G00011 
                 GLN 
                 154 
                 5 
                 100 
                 9 
                 2 
                 72 
                 16 
                 No 
               
               
                   
                 G00011 
                 PRO 
                 156 
                 3 
                 100 
                 1 
                 1 
                 53 
                 16 
                 No 
               
               
                   
                 G00011 
                 GLN 
                 117 
                 4 
                 100 
                 4 
                 2 
                 44 
                 13 
                 No 
               
               
                   
                 G00012 
                 THR 
                 152 
                 5 
                 100 
                 8 
                 2 
                 67 
                 21 
                 No 
               
               
                   
                 G00012 
                 GLU 
                 150 
                 7 
                 100 
                 8 
                 2 
                 96 
                 21 
                 No 
               
               
                   
                 G00014 
                 THR 
                 152 
                 5 
                 100 
                 8 
                 2 
                 67 
                 21 
                 No 
               
               
                   
                 G00014 
                 GLU 
                 150 
                 3 
                 100 
                 12 
                 2 
                 96 
                 21 
                 No 
               
               
                   
                 G00014 
                 ARG 
                 153 
                 4 
                 100 
                 20 
                 2 
                 159 
                 25 
                 No 
               
               
                   
                 G00015 
                 PHE 
                 102 
                 3 
                 100 
                 13 
                 4 
                 27 
                 12 
                 No 
               
               
                   
                 G00016 
                 TRP 
                 151 
                 1 
                 100 
                 4 
                 3 
                 18 
                 10 
                 No 
               
               
                   
                 G00016 
                 GLU 
                 150 
                 6 
                 100 
                 24 
                 5 
                 59 
                 13 
                 No 
               
               
                   
                 G00016 
                 THR 
                 149 
                 3 
                 100 
                 12 
                 3 
                 38 
                 10 
                 No 
               
               
                   
                 G00016 
                 ARG 
                 153 
                 5 
                 100 
                 28 
                 5 
                 60 
                 11 
                 No 
               
               
                   
                 G00016 
                 GLY 
                 140 
                 2 
                 100 
                 19 
                 6 
                 62 
                 19 
                 No 
               
               
                   
                 G00016 
                 GLN 
                 141 
                 5 
                 100 
                 26 
                 5 
                 82 
                 17 
                 No 
               
               
                   
                 G00017 
                 GLN 
                 141 
                 4 
                 100 
                 27 
                 5 
                 82 
                 17 
                 No 
               
               
                   
                 G00017 
                 PRO 
                 142 
                 2 
                 100 
                 16 
                 5 
                 32 
                 14 
                 No 
               
               
                   
                 G00017 
                 ARG 
                 153 
                 5 
                 100 
                 28 
                 5 
                 60 
                 11 
                 No 
               
               
                   
                 G00017 
                 GLU 
                 150 
                 4 
                 100 
                 26 
                 5 
                 59 
                 13 
                 No 
               
               
                   
                 G00017 
                 THR 
                 152 
                 4 
                 100 
                 16 
                 4 
                 34 
                 10 
                 No 
               
               
                   
                 G00018 
                 PRO 
                 156 
                 4 
                 100 
                 2 
                 1 
                 14 
                 6 
                 No 
               
               
                   
                 G00018 
                 LEU 
                 158 
                 3 
                 100 
                 0 
                 0 
                 14 
                 8 
                 No 
               
               
                   
                 G00018 
                 ARG 
                 153 
                 7 
                 100 
                 26 
                 5 
                 60 
                 11 
                 No 
               
               
                   
                 G00018 
                 PHE 
                 155 
                 2 
                 100 
                 3 
                 2 
                 11 
                 5 
                 No 
               
               
                   
                 G00018 
                 LYS 
                 169 
                 4 
                 100 
                 4 
                 1 
                 6 
                 5 
                 Yes 
               
               
                   
                 G00020 
                 ARG 
                 137 
                 1 
                 100 
                 6 
                 5 
                 26 
                 16 
                 No 
               
               
                   
                 G00020 
                 TYR 
                 177 
                 6 
                 100 
                 27 
                 4 
                 158 
                 24 
                 Yes 
               
               
                   
                 G00020 
                 GLU 
                 162 
                 3 
                 100 
                 6 
                 2 
                 49 
                 18 
                 Yes 
               
               
                   
                 G00020 
                 ALA 
                 160 
                 2 
                 100 
                 10 
                 4 
                 44 
                 19 
                 Yes 
               
               
                   
                 G00020 
                 ARG 
                 175 
                 4 
                 100 
                 18 
                 3 
                 90 
                 21 
                 Yes 
               
               
                   
                 G00020 
                 GLN 
                 139 
                 5 
                 100 
                 15 
                 7 
                 77 
                 21 
                 Yes 
               
               
                   
                 G00020 
                 TRP 
                 96 
                 1 
                 100 
                 1 
                 1 
                 9 
                 8 
                 No 
               
               
                   
                 G00020 
                 GLU 
                 138 
                 4 
                 100 
                 8 
                 4 
                 66 
                 20 
                 No 
               
               
                   
                 G00020 
                 ARG 
                 101 
                 1 
                 100 
                 14 
                 2 
                 82 
                 17 
                 No 
               
               
                   
                 G00020 
                 SER 
                 136 
                 2 
                 100 
                 2 
                 1 
                 7 
                 7 
                 No 
               
               
                   
                 G00020 
                 GLY 
                 140 
                 2 
                 100 
                 19 
                 6 
                 62 
                 19 
                 No 
               
               
                   
                 G00021 
                 GLU 
                 150 
                 9 
                 100 
                 21 
                 5 
                 59 
                 13 
                 No 
               
               
                   
                 G00021 
                 THR 
                 149 
                 4 
                 100 
                 11 
                 3 
                 38 
                 10 
                 No 
               
               
                   
                 G00022 
                 THR 
                 93 
                 5 
                 100 
                 9 
                 3 
                 64 
                 20 
                 No 
               
               
                   
                 G00022 
                 TYR 
                 177 
                 10 
                 100 
                 7 
                 1 
                 145 
                 25 
                 Yes 
               
               
                   
                 G00022 
                 GLU 
                 179 
                 10 
                 100 
                 9 
                 3 
                 129 
                 20 
                 Yes 
               
               
                   
                 G00026 
                 TRP 
                 151 
                 1 
                 100 
                 4 
                 3 
                 18 
                 10 
                 No 
               
               
                   
                 G00026 
                 GLU 
                 150 
                 5 
                 100 
                 25 
                 5 
                 59 
                 13 
                 No 
               
               
                   
                 G00026 
                 ARG 
                 153 
                 8 
                 100 
                 25 
                 5 
                 60 
                 11 
                 No 
               
               
                   
                 G00026 
                 GLN 
                 154 
                 3 
                 100 
                 13 
                 4 
                 25 
                 5 
                 No 
               
               
                   
                 G00026 
                 THR 
                 152 
                 6 
                 100 
                 14 
                 4 
                 34 
                 10 
                 No 
               
               
                   
                 G00031 
                 THR 
                 178 
                 4 
                 100 
                 7 
                 1 
                 55 
                 20 
                 Yes 
               
               
                   
                 G00031 
                 GLU 
                 179 
                 3 
                 100 
                 19 
                 3 
                 92 
                 19 
                 Yes 
               
               
                   
                 G00031 
                 TYR 
                 177 
                 8 
                 100 
                 25 
                 4 
                 158 
                 24 
                 Yes 
               
               
                   
                 G00031 
                 ARG 
                 175 
                 5 
                 100 
                 17 
                 3 
                 90 
                 21 
                 Yes 
               
               
                   
               
            
           
         
       
     
     In order to identify which of the clusters describe the true binding sites, a series of mutations would be suggested to key residues. Due to the high number of clusters it was advantageous to identify mutations which were capable of testing multiple clusters concurrently. All the residues identified for all the clusters of a single antibody were analysed to achieve this. The idea was that multiple clusters would be put into combinations and residues that play a major role in all of their potential binding modes be suggested as mutantations to concurrently test many conformations. These combinations were identified by inspecting the overlapping significantly involved residues (those occurring in the top 3 proportions of each cluster.) If clusters shared multiple significantly involved residues they were taken as possible combinations. As exemplified herein, mutations were suggested for C4608 and C5511. These antibodies had 21 and 7 clusters respectively, in order to cluster these, the represented residues from all these clusters were analysed. An inspection of the representative overlaps of significantly occurring residues suggested possible combinations of G00001-G00004-G00007-G00010-G00015, G00012-G00014-G00016-G00017-G00018-G00021-G00026, G00005-G00008-G00020-G00022-G00031 and G00011-G00012-G00014-G00018 for C4608 and possible combinations of G00001-G00005-G00011-G00019-G00020 with G00015 and G00017 by themselves for C5511. Strategy described above was adapted for all anti-CLEC2D antibodies. 
     To identify which residues played a role in combinations of clusters every possible combination of lengths varying from 2 to 13 cluster (depending on the total number of initial clusters available) were generated. For every combination, all the involved residues along with their impact values were identified. Residues that were involved in all or a majority (at most missing in two members) of the members of the combination were retained while the residues that only played a role in some of the clusters in the combination were removed from consideration, leaving only a list of highly occurring residues. 
     Once a preferable combination was identified based on the overlap of residues the residues that were highly occurring for that combination were scrutinized and residues that were observed to have a high impact value were put forward as mutation options ( FIGS. 16E and 16G ). 
     The picks made after all those considerations would possess all the following properties, (a) Be charged or polar residues (although if no such residues were observed other were selected based on their impact on the interaction.), (b) Be present in all or most of the clusters of a combination, (c) Have a significant on the potential binding mode, and (d) involve the antigen-interacting residues 
     As exemplified by C4608, wherein the above described strategy was adopted and following combinations of residues are believed to be involved in interaction with CLEC2D antigen. The similar method was justifyably adopted for all anti-CLEC2D antibodies as well. 
     
       
         
           
               
             
               
                 TABLE 34 
               
             
            
               
                   
               
               
                 The final set of selections of the combinations identified for Antibody clone C4608 
               
            
           
           
               
               
               
               
               
               
               
               
            
               
                   
                   
                   
                   
                   
                   
                 Present  
                 Unique 
               
               
                   
                   
                 Remaining 
                 Residue 
                 Average 
                   
                 on all  
                 to 
               
               
                 Clone Number 
                 Clusters 
                 Clusters 
                 position 
                 Impact 
                 Impact 
                 Clusters 
                 clusters 
               
               
                   
               
            
           
           
               
               
               
               
               
               
               
               
            
               
                 C4608 
                 G00001 
                 G00005 
                 101:ARG:A 
                 −1092.6 
                 yes 
                 yes 
                 no 
               
               
                   
                 G00004 
                 G00008 
                   
                   
                   
                   
                   
               
               
                   
                 G00007 
                 G00011 
                   
                   
                   
                   
                   
               
               
                   
                 G00010 
                 G00012 
                   
                   
                   
                   
                   
               
               
                   
                 G00015 
                 G00014 
                   
                   
                   
                   
                   
               
               
                   
                   
                 G00016 
                   
                   
                   
                   
                   
               
               
                   
                   
                 G00017 
                   
                   
                   
                   
                   
               
               
                   
                   
                 G00018 
                   
                   
                   
                   
                   
               
               
                   
                   
                 G00020 
                   
                   
                   
                   
                   
               
               
                   
                   
                 G00021 
                   
                   
                   
                   
                   
               
               
                   
                   
                 G00022 
                   
                   
                   
                   
                   
               
               
                   
                   
                 G00026 
                   
                   
                   
                   
                   
               
               
                   
                   
                 G00031 
                   
                   
                   
                   
                   
               
               
                   
                 G00012 
                 G00005 
                 150:GLU:A 
                 −382.44 
                 no 
                 yes 
                 no 
               
               
                   
                 G00014 
                 G00008 
                 154:GLN:A 
                 −379.74 
                 no 
                 yes 
                 no 
               
               
                   
                 G00016 
                 G00011 
                   
                   
                   
                   
                   
               
               
                   
                 G00017 
                 G00020 
                   
                   
                   
                   
                   
               
               
                   
                 G00018 
                 G00022 
                   
                   
                   
                   
                   
               
               
                   
                 G00021 
                 G00031 
                   
                   
                   
                   
                   
               
               
                   
                 G00026 
                   
                   
                   
                   
                   
                   
               
               
                   
                 G00005 
                 G00011 
                 175:ARG:A 
                 −710.34 
                 yes 
                 yes 
                 no 
               
               
                   
                 G00008 
                   
                 177:TYR:A 
                 −1056.29 
                 yes 
                 yes 
                 no 
               
               
                   
                 G00020 
                   
                 179:GLU:A 
                 −612.15 
                 yes 
                 yes 
                 no 
               
               
                   
                 G00011 
                 — 
                 150:GLU:A 
                 −544.91 
                 yes 
                 yes 
                 no 
               
               
                   
                 G00012 
                   
                 152:THR:A 
                 −577.26 
                 yes 
                 yes 
                 no 
               
               
                   
                 G00014 
                   
                 153:ARG:A 
                 −649.57 
                 yes 
                 yes 
                 no 
               
               
                   
                 G00018 
                   
                 154:GLN:A 
                 −568.9 
                 yes 
                 yes 
                 no 
               
               
                   
               
            
           
         
       
     
     Construct generation as soluble CLEC2D variants 
     Once the amino acids, which are in combination or independently, are either overlapping or non-overlapping with CD161 interaction points, were generated as CLEC2D antigen variants to map the epitope for novel anti-CLEC2D antibody clones. The constructs were generated either by site directed mutagenesis or by gene synthesis. All constructs were having C-term histidine tag, similar to soluble CLEC2D antigen used for screening, to facilitate the further purification. All possible positions were changed into amino acid alanine, as the observed in silico mutation impact was seen to be maximum for the said amino acid. Table 35 describes positions in CLEC2D soluble antigen wherein the mutations were introduced. 
     
       
         
           
               
             
               
                 TABLE 35 
               
               
                   
               
               
                 Positions for mutation 
               
               
                   
               
             
            
               
                 P128A 
               
               
                 S129A 
               
               
                 D130A  
               
               
                 Q139A 
               
               
                 E162A 
               
               
                 Y165A 
               
               
                 K169A 
               
               
                 S173A 
               
               
                 R175A 
               
               
                 Y177A 
               
               
                 T178A 
               
               
                 E179A 
               
               
                 R180A 
               
               
                 K181A 
               
               
                 K169A &amp; S172A 
               
               
                 Y165A &amp; N167A 
               
               
                 R101A 
               
               
                 Q141A 
               
               
                 R153A 
               
               
                 S187A 
               
               
                 H190A 
               
               
                 R175A, Y177A, E179A 
               
               
                 R084A, H190A 
               
               
                 E150A, T152A, R153A, 
               
               
                 Q154A 
               
               
                 R101A, S105A, 
               
               
                 D107A, H190A 
               
               
                 Q141A, R153A 
               
               
                 D092A, T093A, K094A 
               
               
                 Q141A, K144A 
               
               
                 E138A, C176A 
               
               
                 E138A, Q139A, Q141A, 
               
               
                 R175A 
               
               
                 D092A, Y177A, K181A 
               
               
                 F116A, R153A, 
               
               
                 T093A, N095A 
               
               
                 T093A, Y177A, E179A 
               
               
                 K094A, R101A, E179A 
               
               
                 R175A, Y177A, R180A 
               
               
                   
               
            
           
         
       
     
     As exemplified herein, site directed mutagenesis was performed using QuikChange Lightning Site-Directed Mutagenesis Kit from Agilent by PCR using synthesizing two complimentary oligonucleotides containing the desired mutation, flanked by unmodified nucleotide sequence, which were synthesized at Eurofins. PCR was performed on an Eppendorf™ Mastercycler™ pro PCR System in 25-μL volumes consisting of 0.2 μM of each primer (Eurofins, India), 1.5 μL of Quick solution, 1 μL Quickchange XL dNTP mix, 10× quick change lightening buffer 2.5 μL. Also included were template DNA 15 ng. Following an initial denaturation at 95° C. for 2 min, 18 cycles of 20 seconds denaturation at 95° C., and 60 seconds annealing at 60° C., 3 minutes primer extension at 68° C., 5 minutes final extension at 68° C. were performed. After PCR 2 μL of Dpn I endonuclease was added which is specific for methylated and hemimethylated DNA and is used to digest the parental DNA template and to select for mutation-containing synthesized DNA (DNA isolated from almost all  E. coli  strains is dam methylated and therefore susceptible to Dpn I digestion.) The nicked vector DNA containing the desired mutations was then transformed into XL10-Gold ultracompetent cells and plated onto ampicillin-containing LB agar plates. Plasmid DNA from transformed colonies was purified by QIAprep Spin Miniprep kit (Qiagen) and sequenced at Eurofins. 
     Vector and the SDM construct having specific mutation were restriction endonuclease activity with HindIII and XhoI enzymes and product was extracted using QIAquick Gel Extraction kit, ligated using T4 DNA ligase (NEB) and 50% of mixture were transformed into NEB5α competent cells  E. coli . Subsequently clone screening was carried out through restriction digestion and finally through sequencing reaction. Sequencing process confirmed the clones to contain desired mutation. 
     Anti-CLEC2D antibody mediated blocking of CLEC2D and CD161 interaction. Further probing into observations made from epitope mapping studies prompted to the fact that anti-CLEC2D antibody binding sites on CLEC2D antigen comprises of contact points having both unique/exclusive contact points established on CLEC2D antigen and binding sites overlapping with contact points established between CLEC2D-CD161 complex. As exemplified herein, epitope patches on CLEC2D antigen for C4608 ( FIG. 16A  and  FIG. 16B ) and C5511 ( FIG. 16C  and  FIG. 16D ), not limited to, has been represented wherein binding sites for both C4608 and C5511 anti-CLEC2D antibodies interacting with CLEC2D antigen overlaps significantly with contact points between CLEC2D antigen and CD161. Present disclosure explores the impact of identified anti-CLEC2D antibody on the interaction between CLEC2D and CD161 proteins. As tumour cell evades immune system through the said interaction between CLEC2D and CD161, therefore, experimental validation of CLEC2D binder i.e., anti-CLEC2D antibody disrupting the interaction has been further proved below. Experimental details starts with confirmation of CLEC2D and CD161 interaction followed by abrogating the same by the use of anti-CLEC2D antibody. 
     As exemplified herein, CLEC2D antigen was conjugated on magnetic beads wherein, 1 ml of 0.1 M phosphate buffer saline was added in to 0.5 mg Dynabeads and vortexed for 30 seconds followed by incubation at rotation, at RT for 10 minutes. After incubation, beads were washed twice with 1 ml of 0.1 M phosphate buffer saline with the help of Dynamag 2, then washed beads were resuspended in to 100 μl of 0.1 M PBS. To conjugate antigen on magnetic beads, 100 μl of washed beads and 100 μl PBS containing 1 μg of CLEC2D antigen were mixed thoroughly in the presence of 100 μl of 3 M ammonium sulphate then incubated at 37° C. for overnight. Overnight incubated mix was washed twice with PBS and blocked with 100 μl PBS containing 0.5% BSA for 2 hrs followed by separation of magnetic beads with Dynamag 2. 
     Finally conjugated antigen beads were resuspended in to 100 μl PBS. To check the identity of antigen, 1 μl of above conjugated antigen bead was resuspended in to 99 μl of 1×PBS and washed once with 0.1 M PBS and again resuspended in to 100 μl of 1×PBS. 0.5 μg of anti-CLEC2D monoclonal antibody, commercially available from Novus Biologicals was added in to 100 μl washed conjugated antigen beads then incubated on ice for 2 hrs with constant tapping. After incubation, conjugated antigen beads were washed twice with 100 μl of 1×PBS containing 0.25% BSA then 100 μl of 5 μg/ml Alexa Fluor 488 goat anti-mouse IgG (H+L) was added in to conjugated antigen beads and further incubated for 30 min on ice. After incubation, conjugated antigen beads were washed twice with 100 μl of 1×PBS containing 0.25% BSA and resuspended in to 200 μl of 1×PBS. Fluorescence of all samples including controls were read through CytoFLEX. Bead conjugation efficiency was found to be &gt;95% as judged by flow cytometry analysis as depicted in ( FIG. 16E ). 
     To check the binding of CD161-Fc with CLEC2D antigen, 2 μl of above conjugated CLEC2D antigen beads was taken and different concentrations of CD161-FC (purchased from Biolegend) was added and incubated on ice for 2 hrs with constant tapping to avoid settling of beads. After incubation, the beads was washed twice with 100 μl of PBS with 1% BSA. 100 μl of 5 μg/ml of alexa fluor goat anti human IgG, was added and incubated on ice for 20 min on rotation. The beads was washed once with 100 μl of PBS with 1% BSA and resuspended with 100 μl of 1×PBS. Fluorescence of all samples including controls was read through CytoFLEX. As can be seen from  FIG. 16F , CLEC2D antigen conjugated on magnetic beads interacts in a dose dependent manner to CD161 protein. 
     0.5 μg biotinylayted CD161-FC was added in to 2 μl of CLEC2D conjugated beads and incubated on ice for 2 hrs. After incubation the beads were washed twice with 100 μl of PBS containing 1% BSA and 200 ng of Streptavidin, Alexa Fluor™ 633 conjugate was added and further incubated on ice for 20 min. After incubation the beads were washed twice with 100 μl PBS containing 1% BSA and 2 μg of C5511 antibody was added for 2 hrs on ice. After 2 hrs incubation, 5 μg/ml of alexa fluor goat anti human IgG was added and further kept for 20 min on ice with rotation. Finally fluorescence of all samples including controls were read through CytoFLEX. Loss of signal CLEC2D-CD161 interaction at optimal concentration of anti-CLEC2D antibody as seen in  FIG. 16G , indicates that anti-CLEC2D antibody can compete with CLEC2D-CD161 contact sites and disrupt the interaction. 
     Immune Cell Activation: Due to Binding of Anti-CLEC2D Antibody 
     The prevailing view of NK cell activation is their ability to distinguish healthy cells from sensitive target cells through a balance between signals from activating and inhibitory receptors. The net output of major positive and negative signalling events is viewed to determine the capacity of NK cells to kill target cells. However, the precise molecular check-points where inhibitory signals abrogate activating pathways are not well defined. 
     However, attempts towards delineating the contribution of individual receptors to NK cell activation, CD 69 surface receptor was considered as an early activation immune cells marker which gets rapidly induced in NK cells shortly after activation. CD69 promoter contains binding site for NF-κB, erythroblast transformation-specific related gene-1 (ERG-1) and AP-1. Its expression is upregulated upon activation in most leukocytes and use as a marker of activated lymphocytes and NK cells. In addition CD69 is also an important regulator of immune responses. CD69 is involved in NK-cells activation via Syk-Src-dependent manner. Whereas in T-cells CD69 is induced after TCR/CD3 engagement where it negatively regulates TH1/TH17 response and control inflammation in vivo also through TGF-B signaling. However in NK cells CD69 cross linking has been shown to induce cytotoxic activity and cytokines production of activated NK cells. Thereby, CD69 can be represented as a putative receptor for target cells in activated NK cells. Effector cells used in this study, PBMC and NK cells, as applicable, were isolated using protocol as described above. 
     In order to understand the impact of Anti-CLEC2D antibody on NK cell status, level of CD69 marker expression on NK cells were monitored in the presence and absence of Anti-CLEC2D antibody. For each reaction 0.1×10 6  of isolated NK cells were taken. IL-2 was used as positive control. 200 U of IL-2 (Acro biosystems) and anti-CLEC2D 100 μg/mL and 200 μg/mL was added to each well and incubated overnight. In order to understand the change in CD69 expression through PC3 priming, PC3 cells were added at 1:1 (T:E) ratio to NK cells with or without anti-CLEC2D antibody C5511. NK cells without any treatment or targets were kept as control. Post 12-16 hrs of incubation, CD markers not limited to, anti human CD3-FITC and anti human CD69-APC750 (Biolegend) staining was done 0.5 uL of respective antibodies were used against 0.1×10 6  cells. Cells were washed once with 1×PBS 0.2% BSA and reading was taken using CytoFLEX (Beckman Coulter). Data was acquired using default gain settings and 5000-10000 events were recorded per sample. 
     The results showed 40-50% upregulation of CD69 expression as observed in NK cells in presence of C5511 antibody (100 μg/mL and/or 200 μg/mL) when compared to NK control without treatment wherein the baseline expression was recorded to be 1-2% ( FIG. 17A ). IL-2 was used as positive control and showed 30-40% upregulation ( FIG. 17A ). In case of tumor (PC3) primed NK cells showed high expression close to 70-75% expression of CD69 while CD69 expression was upregulated to ˜85% in presence of both PC3 cell and antibody 100 μg/mL, ( FIG. 17B ). 
     Secretion/Intra-Cellular Expression of Cytokine/Chemokines 
     NK cells recognition of tumor cells/infected cells induces cytotoxicity and cytokines secretion. Signaling pathways which regulates the cytokines production and the contribution of NK cell activation receptor upon target cell recognition for the process is not well understood. In addition the condition/requirement of cytokines secretion on engagement of specific ligand in target cells is not known. Thereby, to understand the primary initiation of immune response upon target cell recognition by NK cells profile/screening of cytokines and chemokines are important. Here, the study was designed to detect cytokine secretion in presence of novel antibody C5511. IFN-γ and TNF-α are the two of the most prominent cytokines produced by NK cells and has been implicated in both cytotoxicity and proliferation of various immune cells. Thereby in this study experiments were conducted to detect IFN-γ secretion in PBMCs or isolated NK-cells by a well-established intracellular IFN-γ staining technique on flow based assay. 
     Cells Stimulation and IFN-γ Staining Protocol: 
     After overnight rest of PBMCs and NK cells at 37° C., the activation reagents and secretion inhibitor (Brefeldin A (10 μg/mL)/Monensin (6 μg/mL)) was added to the well. PBMCs and NK cells were left untreated or treated with novel antibody C5511 at 100 μg/mL. Cells were stimulated with anti human OKT-3 (1-2 μg/mL) as a positive control, as it is known to induce IFN-γ secretion. Target cells, at an effector to target ratio of 10:1 was used whenever required. Medium alone served as the negative control. Cells were incubated for 4 hours at 37° C., in CO2 incubator. 
     After incubation EDTA to a final concentration of 2 mM was added and incubated for 15 min at room temperature. Wash the cells with PBS at 1600 rpm, 8 min at room temperature. PBS wash was repeated at 1600 rpm, 8 min, room temperature and resuspend in 500 μl PBS. Anti-CD3 (Biolegend) cocktail for each sample (20 μl in final) was added. Compensation was done for appropriate amount of single antibodies for compensation controls. Cells were incubated for 30 min at room temperature in the dark. 2 ml of FACS buffer was added to each well tube. Cells were washed twice with FACS buffer at 1600 rpm, 8 min, room temperature. Cells are then re-suspended in 100 μl of flow buffer (0.1% BSA in DPBS) with or 250 μl/tube of BD cytofix/cytoperm, was incubated for 15 min at RT. Cells were then centrifuged at 2000 rpm for 8 min at 4° C. and supernatant was discarded. 
     Cells were washed twice in wash buffer. Supernatant was discarded and IFN-γ PE (Invitrogen) intracellular staining was done as per manufacturer&#39;s protocol. Cells were incubated for 30 min-60 min, on ice, in the dark. After the incubation cells were washed twice with 1 ml of FACS buffer. Supernatant was discarded and resuspend in a final volume of 150 μl FACS buffer for Flow. 
     As can be seen from  FIG. 18A , release of IFN-γ in PBMCs when induced with C5511, anti-CLEC2D antibody, at a concentration of 100 μg/mL was found to be ˜2.97% as compared to uninduced control. Anti OKT-3 antibody, an anti CD3 antibody conjugated with FITC, was used as a positive control, showed 3-6% IFN-γ release when compared with uninduced PBMC ( FIG. 18A ). Subsequently PBMC cells were gated based on CD3+ive and −ive populations wherein CD3+ cells from total PBMC showed non-significant increase of IFN-γ release when treated with Anti-CLEC2D antibody, either alone or with target cells (at T:E ratio 1:10) ( FIG. 18B ). On the contrary, CD3−ive population exhibited significant increase of IFN-γ release upon treatment with Anti-CLEC2D antibody ( FIG. 18C ). It should be noted here that there was no or low increase in IFN-γ production in PC3 primed effector cells, either with whole PBMC or CD3+ cells or CD3− cells. Extending the observation to isolated NK cells, IFN-γ release experiments were performed wherein 1-2% of IFN-γ release, to an approximate, was monitored in the presence of Anti-CLEC2D antibody ( FIG. 18D ). Taken together, release of cytokine, such as IFN-γ, was elevated upon treatment of anti-CLEC2D antibody, as described in present disclosure. The said observation mediated through anti-CLEC2D antibody is subject to binding to CLEC2D antigen, expressed on effector cells, not limited to CD3-/NK cells, suggesting an independent pathway towards activation of other immune cells and essentially effective clearance of target cells. 
     Cytotoxicity Mechanism: 
     To understand the functional role of Anti-CLEC2D antibody in the cytotoxicity mechanism, anti-CLEC2D isotype variants were constructed and assessed in cytotoxicity assay. 
     Generation Relevant Isotype Constructs 
     As exemplified, mammalian expression vector pZB013 (accession # MTCC 25364) with IgG1, N-&gt;A mutation and pZB014 (accession # MTCC 25365) with IgG4 were generated, wherein selected anti-CLEC2D variable heavy chain region could be cloned. Subsequently said constructs with variable heavy chain and pZB008 (accession # MTCC 25359) with variable light chains, will be transfected, expressed and purified for subsequent experimentation. Both the mammalian constructs pZB013 with IgG1, N-&gt;A mutation and pZB014 with IgG4 were custom designed and synthesized ( FIGS. 19A and 19B ). The plasmid which carries a kanamycinR/puromycinR cassette driven by strong promoter and high-copy-number ColE1/pMB1/pBR322/pUC origin of replication for propagation. The variable heavy chain can be replaced using restriction enzyme AscI and XbaI. The variable light chain can be replaced by restriction enzyme EcoRI and AscI. 
     As exemplified herein, PCR was performed using sequence specific primers which were synthesized at Eurofins, and pZB014 and pZB008 vectors were restriction endonuclease activity with respective enzymes and the PCR amplified product was extracted using QIAquick Gel Extraction kit, infusion cloning was done using Infusion HD Cloning Plus CE from and 50% of mixture were transformed into Stellar competent cells  E. coli  and plated onto Kanamycin—containing LB agar plates. Plasmid DNA from transformed colonies was purified by QIAprep Spin Miniprep kit (Qiagen) and sequenced at Eurofins and large scale plasmid was isolated and used for transfection. Herein, Transformation of plasmid DNA into bacterial cell by heat shock method and Plasmid DNA Isolation from bacterial cells using QIAGEN kit and clone screening was similar to as described in section above. All clones were subsequently sequence verified and found to be error free. Respective anti CLEC2D clones in both IgG4 and/or IgG1 mutant formats, were isolated in large scale for transfection into mammalian expression system, CHO cells. 
     CHO Cell Transfection to Express Novel Anti-CLEC2D Monoclonal Antibody IgG4 Variants: 
     As exemplified, for transfection, cell count and viability data was collected using Vi-cell XR automated cell counter, Beckman coulter. Transfection was carried out as per manufacturer&#39;s protocol Lipofectamine® LTX Reagent with PLUS Reagent. Required volume of cell suspension was centrifuged at 1400-1500 RPM for 4-5 mins and re-suspended in specified volume of OPTIMEM I as per Table 36 in 125 ml shake flask. Transfection mix was prepared as per Table 3. Refer Table A for DNA details. 2-3 days post transfection 10 ml Power CHO2 CD growth media was added and Glutamax was added from 200 mM stock to achieve final concentration of 2 mM. Day 6 post transfection, cell culture supernatant was harvested by centrifugation at 1400-2000 rpm for 10-15 minutes. IgG4 antibody variants were purified from cell culture supernatant by Protein A affinity chromatography. 
     
       
         
           
               
             
               
                 TABLE 36 
               
             
            
               
                   
               
               
                 Example of transfection with IgG4 constructs 
               
            
           
           
               
               
               
            
               
                   
                 Parameters 
                 Details 
               
               
                   
                   
               
               
                   
                 Total volume of transfection 
                 50 ml 
               
               
                   
                 Cell density 
                 1.25 ×10{circumflex over ( )}6 cells/ml 
               
               
                   
                 OPTIMEM I 
                 12.5 ml 
               
               
                   
                 Total DNA 
                 25 μg 
               
               
                   
                 HC:LC 
                 1:3 
               
               
                   
                 Amount of DNA: Lipofectamine 
                 1:3 
               
               
                   
                 Amount of DNA: Plus reagent 
                 1:1 
               
               
                   
                   
               
            
           
         
       
     
     As exemplified by, C4701, C3276, C3256 clones, not limited to, were transfected for further purification and evaluation in cytotoxicity assay. 
       
     
       
         
           
               
             
               
                 Lengthy table referenced here 
               
             
            
               
                 US20200291120A1-20200917-T00001 
               
               
                 Please refer to the end of the specification for access instructions. 
               
            
           
         
       
     
     Antibody Mediated Cytotoxicity 
     Post purification, anti-CLEC2D antibody clones were assessed for cell surface binding on C4548 cells using flow cytometry. As can be seen from  FIG. 19C , both clones with IgG4 isotype, exhibited binding towards surface expressed CLEC2D antigen with ˜4-8 fold higher MFI when compared with control un-transfected CHO cell. 
     In order to evaluate functionality of isotype variants, PC3 cells were labelled with Efluor as per the manufacturer&#39;s protocol and were seeded at a density of 0.04×10 6  in 20% DMEM in 24 well plates. After 24 hours, freshly isolated PBMCs were added in T:E of 1:5 and novel monoclonal anti-CLEC2D antibodies C3276, C3256, C3452, and C4608 were added at 100 μg/ml in the assay reaction of 0.5 ml and incubated for 14 hours. Supernatant was collected from 24 well plate and adherent cells were trypsinized and collected in 1.5 ml tubes. Reaction mixture was incubated with sytox green (15 nM) for 20 min and fluorescence was detected in flow cytometer. Percent specific cell death was determined by subtracting the percent cell death of control from the test samples. 
     As can be seen from  FIG. 19D , for C3276, IgG4 variant and C4608 IgG1 variant exhibited similar percentage of cytotoxicity towards PC3 cells. Taken together, both IgG1 and IgG4 variants (treated at 100 μg/ml) showed anti-tumor activity towards PC3 cells signifying an engagement of both CD16 dependent target cell death and also killing of target cells via blocking of CLEC2D and CD161 interaction, in turn suggesting involvement of multiple pathways, probably functions independent of ADCC mechanism, to rapidly kill the tumour cells. In addition, different isotype format of the said antibody, could potentially pave new line of treatment for specific disease, not limiting to, prostate cancer. 
     Impact of Anti-CLEC2D Antibody with Modified Glycosylation on Cytotoxicity 
     The monoclonal antibody based biotherapeutics function through effective recognition of the antigenic epitopes on target cells as well as the antibody effector functions, as an outcome of formation of immune complexes. In recent times, antibody effector function has gained considerable interest towards improving efficacy of the said class of biotherapeutics. Antibody dependent Cellular Cytotoxicity (ADCC) improves clinical efficacy of therapeutic antibodies, the effect is more pronounced in case of anticancer antibodies as exemplified in studies involving allelic polymorphism of leucocyte receptors (FcγR) in patients. Recently, an elegant study with homogeneous IgG glycoforms developed through chemo-enzymatic methods revealed antibody sialylation negatively impacts ADCC in the context of core fucosylation but not in case of nonfucosylated antibody. Multiple studies reported that completely nonfucosylated monoclonal antibody has significantly increased Fc affinity to FcγRIII and thereby improving antibody ADCC function by many folds, in vitro and in vivo. 
     With the advent next generation monoclonal antibody drugs against immune oncology targets, where innate immune system is mobilized to tumor microenvironment, engaging NK cell effector functions becomes immensely important. Any such antibody with improved ADCC functionality recognizing epitopes on tumor cells has the potential to exert more inhibitory effects on tumor cell survival and hence tumor progression. In this context, controlling ADCC function of monoclonal antibody therapeutics helps balancing the optimal effector function to deleterious cytokine release. 
     Afucosylated Anti CLEC2D Antibody Expression: 
     Talen Fut8 gene knockout cell line was developed in GS negative CHO cell line. This cell line was sequence verified for FUT8 gene knock-out and was coded as C2899. C0694 (HC and LC vectors) and C2685 (HC and LC vectors) were transfected in this cell line. Antibiotic selection was performed, Minipools and single cell clones were developed from this cell line which expresses afucosylated anti-CLEC2D antibody. Afucosylated antibodies were tested for cell surface antigen binding on C4548 cells by flow-cytometry and on target cells by confocal imaging. 
     C2899 Cell Transfection to Express Novel Anti-CLEC2D Monoclonal Antibody Clones Transfection: 
     C2899 cells were transfected with C0694 and C2685 heavy chain and light chain vectors. Cell count and viability data was collected using Vi-cell XR automated cell counter, Beckman coulter. Transfection was carried out as per manufacturer&#39;s protocol Lipofectamine® LTX Reagent with PLUS Reagent. Required volume of cell suspension was centrifuged at 1400 RPM for 4 mins and re-suspended in specified volume of OPTIMEM I in 125 ml shake flask. Transfection mix was prepared as described before. C2899 cells transfected with C0694 HC and LC vectors were known as C3234 whereas C2899 cells transfected with C2685 HC and LC vectors were known as C4335. 
     Generation of Stable Cell Lines Expressing Afucosylated Anti-CLEC2D Antibody: 
     Antibiotic Selection: 
     Antibiotic selection was initiated after transfection at &gt;80% cell viability. Cell suspension was centrifuged at 1400 RPM for 4-5 mins. Pellet was re-suspended in complete Power CHO2 growth media and concentration of Puromycin Dihydrochloride was adjusted to 2 μg/1×10{circumflex over ( )}6 cells. Antibiotic selection was carried out on every 2nd or 3rd day. 
     Repeat Transfection of Stable Pool: 
     Cell count was taken using Vi-cell XR. Cells were subcultured before the transfection. Two more sequential transfections were performed as mentioned previously. On completion of three rounds of transfection the pool was designated as R3 stable pool. 
     Minipool Plating: 
     Minipools were generated by serial dilution method. Continuously growing culture of cell line was subcultured at 0.5 million cells/ml in 30 ml complete PowerCHO 2 growth media with 2 mM glutamax, 1 to 2 days before plating. Cell count and viability data was collected using Vi-cell XR. Serial dilution of the cell suspension was carried out in complete PowerCHO2 growth media at 1:10 ratio. Cells were seeded at a density of 10 cells/well in a 96 well plate in 200 μl volume per well in cloning media. These mini-pools were maintained at 37° C. Temperature in a humidified 5% CO2 incubator. 
     Screening of Mini-Pools and Amplification: 
     Mini-pools were screened by flow cytometry wherein binding to C4548 cells was estimated. Minipools were ranked based on cell surface binding. Minipools selected from flow cytometry screening were amplified from 96 well plate to 24 well plate and maintained at 37° C., humidified condition in a 5% CO2 incubator. These were further amplified from 24 well plate to one well of 6 well plate. After cells were confluent mini-pools were amplified from one well of 6 well plate to a 50 ml bioreactor tube or 125 ml Erlenmeyer shake flask with 25-30 ml growth media and maintained at 37° C., humidified condition in a 5% CO2 incubator, 120-200RPM. 
     Single Cell Cloning 
     Single cells were generated by serial dilution method. Continuously growing culture of selected mini-pool was subcultured at 1 million cells/ml in 30 ml complete PowerCHO 2 growth media with 2 mM glutamax, 1-2 day before cloning. Cell count and viability data was collected using Vi-cell XR. Serial dilution of the cell suspension was carried out in complete powerCHO2 growth media at 1:10 ratio. Cells were seeded at a density of 0.5 cells/well in a 96 well plate and maintained at 37° C. Temperature in a humidified 5% CO2 static incubator. Plates were scanned by using CloneSelect Imager (Molecular Devices) for monoclonality report generation from day zero to day ten. The clonal population was confirmed from the day zero image of entire well and the monoclonality report generated by CloneSelect Imager. Passage number was P(x+0). Single cell clones were coded with four digit random numbers. The Single cell clones were amplified to 24 well plates after cells were confluent. Passage number was P(x+1). 
     Screening of Single Cell Clones and Clone Amplification: 
     Cell surface binding assay was performed to estimate antibody in cell culture supernatant and to rank the clones. Single cell clones showing higher binding on C4548 cell surface expressed CLEC2D antigen were amplified from 24 to 6 well. Passage number was (x+2). This was followed by amplification in 3 wells of 6 well plate. Passage number was (x+3). The clones were further amplified to bioreactor tubes or Erlenmeyer flasks. RCB vials were prepared for the clones. 
     Culture Harvest for Protein Purification: 
     Cells were seeded at a density of approximately 0.3×10{circumflex over ( )}6 cells/ml in 30-100 ml Complete power CHO2 growth media and cultured for 6 days in 37° C., humidified condition in a 5% CO2 incubator with 120 RPM rotation. 20% v/v media top-up was given with complete power CHO2 growth media on 3rd or 4th day. Supernatants were harvested by centrifuging the entire cell suspension at 1400-2000 RPM for 10 mins. The supernatants were collected and subjected to purification by protein-A affinity chromatography. 
     Cell Surface Binding Assay by Flow-Cytometry: 
     CHO cells were transiently transfected with CLEC2D surface expression vector. Surface expression was optimum on day 4 to day 5 on transfected cells. These cells were coded as C4548. Cell count was taken by Vi-cell XR automated cell counter. CHO and C4548 cells were centrifuged at 1000-1400 rpm for 4-5 minutes. The pellet was re-suspended in 1 ml DPBS. 50,000 cells were aliquoted in each well of a 96 well plate. 1-5 μg of purified antibody samples and reference control was added to each well and incubated for 40-60 minutes at room temperature (25° C.). The plate was centrifuged at 1000-1400 rpm for 4-5 minutes, the supernatant was aspirated and cells were washed with 0.1% BSA in DPBS. 2.5 ml of 2% BSA was diluted to 50 ml with DPBS. Goat anti human IgG FITC conjugate was used as secondary antibody. 1:100 dilution of secondary antibody was prepared in DPBS and 100 μl was added to each well. The plate was incubated for 30 minutes at room temperature (25° C.) in dark. The cells were washed with 0.1% BSA and re-suspended in 100 μl of 2% BSA. Samples were analyzed by flow-cytometry. 
     Binding of test sample supernatant on un-transfected CHO cells was estimated and used for calculation of specific binding on C4548 cell surface using following formula: 
     
       
         
           
             
               Fold 
                
               
                   
               
                
               change 
                
               
                   
               
                
               in 
                
               
                   
               
                
               M 
                
               
                   
               
                
               F 
                
               
                   
               
                
               I 
             
             = 
             
               
                 
                   
                     
                       Median 
                        
                       
                           
                       
                        
                       FITC 
                        
                       
                         - 
                       
                        
                       A 
                        
                       
                           
                       
                        
                       of 
                        
                       
                           
                       
                        
                       test 
                        
                       
                           
                       
                        
                       sample 
                        
                       
                           
                       
                        
                       on 
                        
                       
                           
                       
                        
                       CHO 
                        
                       
                           
                       
                        
                       cells 
                     
                   
                 
               
               
                 
                   
                     
                       Median 
                        
                       
                           
                       
                        
                       FITC 
                        
                       
                         - 
                       
                        
                       A 
                        
                       
                           
                       
                        
                       of 
                        
                       
                           
                       
                        
                       test 
                        
                       
                           
                       
                        
                       sample 
                        
                       
                           
                       
                        
                       on 
                        
                       
                           
                       
                        
                       C 
                        
                       
                           
                       
                        
                       4548 
                        
                       
                           
                       
                        
                       cells 
                     
                   
                 
               
             
           
         
       
     
     Purified anti-CLEC2D antibody from stable cell clones were firstly assessed for cell surface binding on C4548 cells through flow cytometry, experimentation for flow cytometry based binding studies remains similar as described in Example 5, Section: Cell surface binding assay: through Flow Cytometry and Confocal Microscopy. As can be seen from  FIG. 19E , all clones as exemplified by C0613, C1301, C6268, C1699, C2437, C9832, C8900 and C7749, exhibited differential binding towards surface expressed CLEC2D antigen with ˜2-10 fold higher MFI when compared with control, which is un-transfected CHO cell. 
     Cytotoxicity with Afucosylated Anti-CLEC2D Antibody 
     Confirmed afucosylated anti-CLEC2D mono clonal antibodies were used subsequently for cytotoxicity experiments and effect of glycosylation was compared with fucosylated anti-CLEC2D antibodies. 
     Herein, PC3 cells were labelled with Efluor as per the manufacturer&#39;s protocol and were seeded at a density of 0.04×10 6  in 20% DMEM in 24 well plates. After 24 hours, freshly isolated NK cell was added in T:E of 1:1. Novel monoclonal anti-CLEC2D antibody C5511 (100 μg/ml) and afucosylated mabs C7749, C8800 and C9832 were added at 20 μg/ml in the assay reaction of 0.5 ml and incubated for 14 hours. Supernatant was subsequently collected from 24 well plate followed by trypsinization of adherent cells. Reaction mixture was incubated with sytox green (15 nM) for 20 min and fluorescence signal was detected using flow cytometer. Percent specific cell death was determined by subtracting the percent cell death of control from the test samples. 
       FIG. 19F  depicts the impact of fucsylation on Anti-CLEC2D antibody mediated cytotoxicity as assessed through killing of PC3 cells. As mentioned before, afucosylated Anti-CLEC2D antibodies were used at a concentration that is 5 times lower than fucosylated antibody i.e., C5511. Observed cytotoxicity suggests that afucosylated anti-CLEC2D antibody is at least 5 times more effective when compared with the fucosylated anti-CLEC2D antibody. Thereby, the said and described version i.e., afucosylated anti-CLEC2D antibodies could be used as an efficient alternative treatment/therapy option to achieve increased clinical efficacy. 
     Taken together, functional efficiency of anti-CLEC2D monoclonal antibodies could be ADCC independent, as seen in functionality for said antibody in IgG4 isotype format, while afucosylated version of anti-CLEC2D antibody elicits an efficient ADCC mediated target killing, which in turn elaborates/expands about/on the functional and application related versatility in therapeutic space. 
     Complement Dependent Cytotoxicity 
     Complement-dependent cytotoxicity, or CDC, is a well-known mechanism through which antibodies lyse the unwanted target by activating a cascade of complement-related reactions. Usually IgG1 and IgG3, elicits CDC killing effects via binding its Fc region to serum complement components, particularly Clq. Following complicated enzyme activations and cleavage events, involving over 20 highly regulated elements, it will eventually lead to the formation of membrane attacking complex (MAC), thereby target cell destruction. 
     Specific example details on experimentation wherein 50 μL of target cell suspension (PC3 and Ramos) containing 5×10 4  cells were added to each well of the 96-well assay plate. 50 μL of different concentrations of C5511 antibody (200, 40, 0.4, 0.04 μg/mL) dilution was added to the plate to start the reaction. The plate was shaken for 30 seconds. Baby rabbit complement was then diluted (1:20) in cell medium, and 50 μL was added to the appropriate wells. Following shaking for 30 seconds, the plate was incubated at 37° C., 5% CO2 for 120 minutes. The plate was then removed from the 37° C. incubator and allowed to cool to room temperature (RT) for 15 minutes, and then add 25 μL of warm Risazurin solution and incubate overnight (16-20 hrs) at 37° C., 5% CO2 incubator. The plate was then removed from the 37° C. incubator and allowed to cool to room temperature (RT) for 15 minutes, and then read plate in fluorescence mode (excitation  530  and emission  590 ) using the Synergy HT BIOTEK micro plate reader. 
     The data obtained from both Ramos and PC3 cell line suggests that anti-CLEC2D antibody does not exhibits its cell killing mechanism through CDC pathway as shown in  FIG. 19G . 
     Example 7: In Vivo Mouse Efficacy Studies with Anti-CLEC2D Monoclonal Antibody 
     In Vivo Mouse Efficacy Studies 
     During the development of therapeutic monoclonal antibodies (mAbs), a strategy for early identification of candidate mAbs with the greatest likelihood of success in the clinic is needed to avoid costly late-stage failures related to inadequate exposure, toxicity or lack of efficacy. Early screening and optimization of mAbs focus on characteristics such as affinity, potency and stability for selection of lead constructs, while confirmation on in vivo efficacy are typically required 
     The anticancer activity of anti-CLEC2D monoclonal antibody was evaluated in huNOG-EXL mice bearing subcutaneous PC3 tumor xenografts ( FIGS. 20A and 20B ). The procedure relies on super immune-deficient hGM-CSF/hIL3 transgenic-NOG mice, which upon engraftment with human hematopoietic stem cells, results in human-like immune system (lymphoid &amp; myeloid lineage of human origin). This model enabled an efficacy study of the key innate mechanisms involved in the function of immune-therapy agents. The study was conducted for a period of 4-5 weeks with regular observation of tumor volume and body weight. The study was carried out in accordance with Institutional Animal Ethics Committee (IAEC). 
     All animals were kept for acclimatization for a period of about 5-7 days before initiation of the experiment. Animals were housed group wise (5 animals per cage) in IVCs and autoclaved corncob was used as the bedding material. Animals were maintained in a controlled environment with 22±3° C. temperature, 50±20% humidity, a light/dark cycle of 12 hours each and 15-20 fresh air changes per hour. The animals were fed, ad libitum, with certified Irradiated Laboratory Rodent Diet. 
     
       
         
           
               
               
             
               
                   
               
             
            
               
                 Species 
                 Mus musculus 
               
               
                 Strain 
                 huNOGEXL 
               
               
                 Source 
                 Taconic Biosciences 
               
               
                 Sex 
                 Male 
               
               
                 Age 
                 5-6 weeks 
               
               
                 Body weight 
                 19-21 g 
               
               
                 Cancer cell line 
                 PC3 (Human prostate adenocarcinoma) 
               
               
                 Cell inoculation density 
                 5 × 10 6  cells/animal 
               
               
                 Study initiation 
                 Tumor volume (≈100 mm 3 ) 
               
               
                 Duration of the study 
                 4-5 weeks 
               
               
                 Test item 
                 Anti-CLEC2D antibody clones, IgG1 
               
               
                   
                 control monoclonal antibody, Check  
               
               
                   
                 point monoclonal antibody 
               
               
                 Dose &amp; Dosing schedule 
                 10 mg/kg, 4 intraperitoneal  
               
               
                   
                 dosing-once every 7 days 
               
               
                 Route of dosing 
                 Intraperitoneal 
               
               
                 Tumor volume measurement 
                 Once every three days 
               
               
                 Body weight measurement 
                 Once every three days 
               
               
                   
               
            
           
         
       
     
     All procedures were performed in a laminar flow hood following sterile techniques. PC-3 (Human prostate adenocarcinoma) cells with a viability of &gt;90% was chosen for the study. Around 5×10 6  cells were re-suspended in 200 μl of serum free media containing 50% of matrigel kept in ice. Male huNOG-EXL mice housed in Individually Ventilated Cages (IVCs) were used for the study. The PC-3 cell line was propagated into the animals by injecting the cells subcutaneously in the right flank region of the animals. The implanted area was monitored for growth of tumor. Once the tumor attained palpable stage and required volume (Mean tumor volume 115 mm 3 ), animals were randomized and dosing was initiated with anti-CLEC2D monoclonal antibodies, the IgG1 control monoclonal antibody and check point monoclonal antibody. Antibodies were administered intraperitoneally. The dose of each individual animal was adjusted based on its body weight. 
     The primary objective of the study was to evaluate the antitumor activity of anti-CLEC2D monoclonal antibodies. In addition to the efficacy of the anti-CLEC2D antibody clones alone, experiments were carried out for combination treatment with a check point monoclonal antibody against PDL1 antigen. In huNOG-EXL mice bearing PC-3 tumor xenograft, animal body weight, clinical signs and tumor volume were recorded once every three days throughout the experimental period. The study was constituted with following arms as described in Table 42: 
     
       
         
           
               
               
               
               
             
               
                 TABLE 42 
               
               
                   
               
               
                   
                 Monoclonal 
                   
                 Frequency of 
               
               
                 SI No 
                 antibody 
                 Dosage 
                 treatment 
               
               
                   
               
             
            
               
                 Arm 1 
                 Control human IgG1 
                 10 mg/kg 
                 Once a week 
               
               
                 Arm 2 
                 anti-CLEC2D mAb 
                 10 mg/kg 
                 Once a week 
               
               
                   
                 clone 1 
                   
                   
               
               
                 Arm 3 
                 anti-CLEC2D clone 2 
                 10 mg/kg 
                 Once a week 
               
               
                 Arm 4 
                 Anti PDL1 mAb 
                 10 mg/kg 
                 Once a week 
               
               
                 Arm 5 
                 anti-CLEC2D clone  
                 5 mg/kg of anti-CLEC2D 
                 Once a week 
               
               
                   
                 1 + Anti PDL1 mAb 
                 clone 1 + 5 mg/kg of Anti 
                   
               
               
                   
                   
                 PDL1 mAb 
               
               
                   
               
            
           
         
       
     
     Animals in “Arm 1” revealed progressive tumor growth during the study period. Tumor growth inhibition was observed in all other experimental arms. Individual body weight was measured once every three days during the study period. The percentage change in body weight of individual mouse was calculated and recorded. Animals were observed for visible clinical signs every day during the study period. The tumor volume was determined by two-dimensional measurement with a digital Vernier calliper on the day of randomization (Day 0) and then once every three days (i.e., on the same days when body weight was taken). Using a Vernier calliper the length (L) and width (W) of the tumor was measured. Tumor volume (TV) was calculated using the following formula: 
       TV=(L×W×W)/2; where L=Length (mm); W=Width (mm).
 
     Mean, Standard Deviation (SD) or Standard Error of Mean (SEM) were calculated for individual groups. Antitumor activity was evaluated as maximum tumor volume inhibition versus the control IgG1 arm (Arm 1). Data evaluation was performed using statistical software Graph Pad Prism V 5.0. Tumor growth inhibition (TGI) was calculated using the following formula: 
       TGI=(1−T/C)×100%
 
     where, T=(Mean Tumor volume (TV) of the test arm on Day X−Mean TV of the test arm on Day 0; C=(Mean TV of the control Human IgG (Arm 1) on Day X−Mean TV of the control Human IgG (Arm 1) on Day 0. 
     The relative tumor volume (RTV) and tumor growth inhibition were calculated. Mean±SEM was calculated for the RTV data and tumor growth inhibition was presented as a percentage. Two way ANOVA was utilized for statistical analysis and p value &lt;0.05 between arms was considered significant. The results show significant tumor growth reduction with both monotherapy with anti-CLEC2D antibody and in combination with check point monoclonal antibody against PDL1. 
     Significant tumor growth inhibition was observed in Arm 2, Arm 3, Arm 4 and Arm 5 compared to Arm 1, representing Control human IgG1. It was unexpected that significant tumor growth inhibition over entire study period was observed in animals treated with anti-CLEC2D monoclonal antibody clones, and anti-PDL1 antibody. More interestingly, a completely novel finding where tumor sizes were reduced by half in animals treated with a combination of anti-CLEC2D monoclonal antibody clone and anti-PDL1 monoclonal antibody was observed. This observation is very significant as the combination treatment with anti-CLEC2D antibody and anti-PDL1 antibody achieved this high level of tumor growth inhibition at a reduced dosage of 5 mg/kg. The data indicates significant anti tumor activity when anti-CLEC2D antibody was used alone and when it was used in combination with anti PDL1 antibody, showing that the antibody clones against CLEC2D antigen have great therapeutic potential for various disease indications. 
     During the study period, monoclonal antibody dosages were well tolerated with mild body weight loss. Based on cage side observations there was no visible signs of abnormal behaviour or any adverse clinical symptoms in any of the groups during the experimental period. T cell infiltration to the tumor site was analysed using immunohistochemistry (IHC) of the excised tumor. The harvested tumor cells were subjected to different types of T cell markers to understand the infiltration. Histology processing was conducted for immunohistochemistry for FFPE tissue (Formalin-Fixed Paraffin-Embedded (FFPE) tissue specimens). Animals were euthanized and the tumors were harvested &amp; fixed in 10% neutral buffer formalin for 24 hours. The tissues were subjected to tissue processing. Paraffin embedded tissue blocks were prepared after completion of tissue processing. Subsequently, sectioning blade holder angle was adjusted to the surface of tissue block in the microtome. Coarse trimming was carried out, and fine sections of 5 micron thickness were taken and transferred to the tissue water bath. Formalin-Fixed Paraffin-Embedded (FFPE) tissue specimens were processed for IHC staining with standard reagents. 
     Samples were washed in washing buffer (PBST-0.3% tritonX-100) for 10 min. Samples were incubated with blocking solution (10% Normal goat serum and 3% BSA in PBS) for 30-60 minutes in humidified environment. Primary antibodies were diluted in antibody dilution buffer (3% BSA in PBS). The tissues were incubated with primary antibody against CD3 antigen at 1:100 dilution and incubated overnight at 4° C. Subsequently slides were washed three times in washing buffer for 10-30 minutes/wash. This was followed by incubation with secondary antibody Goat Anti-Rabbit IgG H&amp;L (HRP) at room temperature. Slides were washed three times in washing buffer for 15-30 minutes for each wash. The DAB Chromogen was applied to develop proper intensity of tissue staining. Counterstaining was carried out with hematoxylin. 
     The tumor samples were immunohistochemically stained with anti-CD3 antibody. CD3 cell (Pan T cell marker) infiltration was observed in the periphery of tumor tissues in human IgG control (Arm 1). However, in animals treated with anti-CLEC2D antibody, check point antibody alone, or a combination of anti-CLEC2D antibody with a check point antibody, the CD3 cell infiltration was observed heterogeneously in periphery and also around the tumor cells. CD3, a membranous immunohistochemical marker, revealed mild to moderate degree of staining of tumor samples harvested from animals treated with anti-CLEC2D antibody, check point antibody, and a combination of anti-CLEC2D antibody with check point antibody. The data provides clear insights into the mechanisms of tumor mediated immune suppression 
     Localization of Labelled Anti-CLEC2D Antibody 
     In a separate imaging experiment, anti-CLEC2D antibody labelled with Alexa 647 was administered at a single dose of 10 mg/kg intravenously. The fluorescently labelled antibody was administered to huNOG-EXL mice bearing subcutaneous PC-3 tumor (Mean Tumor volume ˜213 mm 3 ). In-vivo imaging was carried out at 0 min, 5 min, 15 min, 30 min, 1 hr, 3 hr, 6 hr, 12 hr, 24 hr, 48 hr, 72 hr and 96 hr post administration of Alexa 647 labelled antibody ( FIG. 20C ). The monoclonal antibody against anti-CLEC2D antibody exhibited affinity (which was evident from tumor signal intensity) towards the target antigen of interest in huNOG-EXL mice bearing subcutaneous PC-3 tumor. 
     The signal intensity from the tumor appeared as early as 5 minutes post injection of the antibody and gradually increased with time. The peak signal intensity was observed at 3 hrs and the signal intensity from the tumor lasted until 96 hrs. 
     In Vivo Mouse Efficacy with Selected Monoclonal Antibody Products 
     In a separate follow up xenograft mouse study, the monoclonal antibody drug products were tested to evaluate tumor growth reduction upon monoclonal antibody treatment. 
     Origin of the animals: hGM-CSF/hIL3 NOG mice engrafted with human CD34+ hematopoietic stem cells (HSCs) stably develop extensive cell lineages as early as 6 to 8 weeks post-injection. Both myeloid and lymphoid lineage cells are present in peripheral blood, bone marrow, thymus and spleen and non-lymphoid tissue including lung and liver. For the current study huNOG-EXL mice with greater than 25% hCD45+ in peripheral blood were used 
     Rationale: The procedure relies on super immunodeficient the hGM-CSF/hIL3 transgenic-NOG mice which upon engraftment with human hematopoietic stem cells, results in a human-like immune system (lymphoid &amp; myeloid lineage of human origin). This model enables to study the key innate mechanisms involved in the efficacy of immuno-therapy related agents and provide a suitable model for establishment of human xenografts. 
     
       
         
           
               
               
               
             
               
                   
                   
               
             
            
               
                   
                 Strain 
                 huNOG-EXL 
               
               
                   
                 Sex 
                 Male 
               
               
                   
                 Source 
                 Taconic (USA) 
               
               
                   
                 Age at the start of experiment 
                 13-14 weeks 
               
               
                   
                 Body Weight of animals 
                 18-22 g 
               
               
                   
                   
               
            
           
         
       
     
     Animal Care 
     Animal Welfare 
     Animals were taken care as per the regulations of Committee for the Purpose of Control and Supervision of Experiments on Animals (CPCSEA), Government of India and Association for Assessment and Accreditation of Laboratory Animal Care (AAALAC) guidelines. 
     Housing and Feeding 
     Animals were housed in individually ventilated cages maintained in a controlled environment with 22+3° C. temperature, 50+20% humidity, 12 h light/dark cycle and 15-20 fresh air changes per hour. Animals were housed group-wise and autoclaved corncob (Sparconn Life Sciences, Bangalore, India) was used as a bedding material. The animals were fed (NIH-31), ad libitum, with certified irradiated laboratory rodent diet during the study period. 
     Drinking Water 
     Fresh, potable water, filtered through RO, was provided ad libitum after autoclaving to all animals via bottle fitted with nozzle. 
     Preparation of Animals 
     The animals were kept under acclimatization in the experimental room for a period of 10 days. A thorough observation was performed before selecting the animals and only animals that were apparently healthy were used for the study. 
     Animal Identification 
     Animals were individually numbered and the cage cards indicating the experiment, study number, date of randomization, mouse strain, gender and individual mouse numbers were displayed to corresponding cages. After randomization group identity, treatment code, dosage, schedule and route of administration were included in the cage cards. 
     Experimental Procedure 
     Preparation of Tumor Cells 
     All procedures were performed in a laminar flow hood following sterile techniques. PC-3 (Human prostate adenocarcinoma) cells with a viability of &gt;90% was chosen for the study. Around 5×106 cells were re-suspended in 200 μL of serum free media containing 50% of matrigel kept in ice. 
     Subcutaneous Injection of Cells 
     Male huNOG-EXL mice housed in Individually Ventilated Cages (IVCs) were used for the study. PC-3 cell line was propagated into the animals by injecting the cells subcutaneously in the right flank region of the animals. The implanted area was monitored for growth of tumor. Four days post injection of cells animals were randomized based on tumor volume (Mean tumor volume≈37 mm3) and dosing was initiated. 
     Route and Mode of Administration of the Test Substance: 
     Required quantity of test antibodies were prepared and stored at 2-80 C. The antibodies were administered intraperitoneally. The dose of individual animal was adjusted based on the body weight. For each antibody, unused new syringes and needles were used. 
     Experimental Design
         Monoclonal antibody products were used at 10 mg/kg dosage
           a. C5511 mAb group;   b. C6481 mAb group.   
           Vehicle control IgG1 group—Control IgG1 was used at 10 mg/kg dosage.   5 animals per treatment group.   Antibody drug product was injected every 3 days for first 2 weeks and once weekly for remaining study period.   Total study duration 36 days.   Tumor volume measurement and animal body weight measurement was carried out every 3 days.       

     Dose and Route of Administration 
     Required quantity of test compounds (ready to use formulation) were used and it was stored at −200 C. Test compounds were administered intraperitoneally to their respective groups. The dose of each individual animal was adjusted based on the body weight determined just before dosing and dose volume was maintained at 10 mL/kg body weight. For each test compound, sterile new syringes and needles were used. The test compounds were freshly thawed on the day of drug administration. 
     Observations 
     Body weight—Individual body weight was measured once every three days during the study period. The % change in body weight of individual mouse was calculated and recorded. 
     Clinical sign—Animals were observed for visible clinical signs and recorded once in every third day during the treatment period. 
     Tumor volume measurement—The tumor volume was determined by two-dimensional measurement with a digital Vernier calliper on the day of randomization (Day 1). Second tumor volume measurement was on day 3, further every third day till the end of the experiment the tumor volume measurement was carried out (i.e. on the same days when body weight was taken). Using a Vernier calliper the length (L) and width (W) of the tumor was measured. Tumor volume (TV) was calculated using the following formula: 
     
       
         
           
             
               Tumor 
                
               
                   
               
                
               volume 
                
               
                   
               
                
               
                 ( 
                 
                   mm 
                    
                   
                       
                   
                    
                   3 
                 
                 ) 
               
             
             = 
             
               
                 L 
                 × 
                 W 
                  
                 
                     
                 
                  
                 2 
               
               2 
             
           
         
       
     
     Where, L=Length (mm); W=Width (mm). 
     Mean, Standard Deviation (SD) or Standard Error of Mean (SEM) were calculated for individual groups. 
     Antitumor Activity 
     Antitumor activity was evaluated as maximum tumor volume inhibition versus the vehicle control group. Data evaluation was performed using statistical software Graph Pad Prism V 5.0.
         Tumor growth inhibition (TGI)
 
TGI was calculated using the following formula:
       

       TGI=(1−T/C)×100
 
     Where, T=(Mean TV of the test group on Day X−Mean TV of the test group on Day 1) C=(Mean TV of the control group on Day X−Mean TV of the control group on Day 1)
         Relative tumor volume (RTV)
 
Relative Tumor volume (RTV) was calculated using the following formula:
       

     
       
         
           
             
               R 
                
               
                   
               
                
               T 
                
               
                   
               
                
               V 
             
             = 
             
               
                 Tx 
                  
                 
                     
                 
                 ( 
                 
                   absolute 
                    
                   
                       
                   
                    
                   tumor 
                    
                   
                       
                   
                    
                   volume 
                    
                   
                       
                   
                    
                   of 
                    
                   
                       
                   
                    
                   the 
                    
                   
                       
                   
                    
                   respective 
                    
                   
                       
                   
                    
                   tumor 
                    
                   
                       
                   
                    
                   on 
                    
                   
                       
                   
                    
                   day 
                    
                   
                       
                   
                    
                   x 
                 
                 ) 
               
               
                 T 
                  
                 
                     
                 
                  
                 1 
                  
                 
                     
                 
                  
                 
                   ( 
                   
                     absolute 
                      
                     
                         
                     
                      
                     tumor 
                      
                     
                         
                     
                      
                     volume 
                      
                     
                         
                     
                      
                     of 
                      
                     
                         
                     
                      
                     same 
                      
                     
                         
                     
                      
                     tumor 
                      
                     
                         
                     
                      
                     on 
                      
                     
                         
                     
                      
                     day 
                      
                     
                         
                     
                      
                     1 
                   
                 
               
             
           
         
       
     
     Statistical Analysis 
     For the evaluation of the statistical significance of tumor inhibition, Two-way ANOVA followed by Bonferroni post hoc test was performed using Graph Pad Prism V 8.3.0. p values &lt;0.05 indicate statistically significant differences between groups. 
     Necropsy 
     Tumor burden (TV&gt;1500 mm3) and tumor necrosis/ulceration were observed due to progressive tumor growth. Hence, based on tumor end points &amp; ethical reasons (Day 36), all animals in all experimental groups were humanely euthanized &amp; gross pathological observations were recorded. Prior to euthanasia, blood sampling was carried out, serum was separated and stored at −80° C. All live animals &amp; excised tumor tissues were photographed with scale and whole tumor tissues were formalin-fixed. 
     Results Obtained from the In Vivo Studies 
     Antitumor Activity 
     In this study, huNOG-EXL mice bearing PC-3 tumors were treated with test compounds at a dose of 10 mg/kg intraperitoneally (On day 1, 3, 6, 9, 12, 18, 24, 30 &amp; 33). Under the present experimental condition, the vehicle control IgG1 group showed progressive tumor growth during the experimental period. Hence, other treatment groups were compared with this group for anticancer efficacy evaluation. Among the tested dose and regimen, two test arms revealed C5511 mAb group and C6481 mAb group showed significant tumor growth inhibition as p&lt;0.001 and p&lt;0.05 respectively when compared to vehicle control IgG1 on day 24. Whereas, on day 36 only C5511 mAb group exhibited significant tumor growth inhibition as p&lt;0.05 when compared to vehicle control IgG1 group. The data is presented in Table 43. 
     
       
         
           
               
             
               
                 TABLE 43 
               
             
            
               
                   
               
               
                 Effect of test compounds in humanized (huNOG-EXL) mice bearing  
               
               
                 subcutaneous PC-3 tumor xenografts 
               
            
           
           
               
               
               
               
               
               
               
            
               
                   
                 Number of 
                 % TGI 
                 Statistical 
                 % TGI 
                 Statistical 
                 Mean % 
               
               
                 Test 
                 animals/ 
                 (Day 
                 Significance 
                 (Day 
                 Significance 
                 BWC 
               
               
                 Compound 
                 group 
                 24) 
                 (Day 24) 
                 36) 
                 (Day 36) 
                 (Day 36) 
               
               
                   
               
               
                 C5511 mAb 
                 5 
                 49 
                 ***(p &lt; 0.001) 
                 35 
                 *(p &lt; 0.05) 
                 −14 
               
               
                 group 
                   
                   
                   
                   
                   
                   
               
               
                 (10 mg/kg, i.p; 
                   
                   
                   
                   
                   
                   
               
               
                 On day 1, 3, 6, 
                   
                   
                   
                   
                   
                   
               
               
                 9, 12, 18, 24, 
                   
                   
                   
                   
                   
                   
               
               
                 30 &amp; 33) 
                   
                   
                   
                   
                   
                   
               
               
                 Vehicle 
                 5 
                 — 
                 — 
                 — 
                 — 
                 −21 
               
               
                 Control IgG1 
                   
                   
                   
                   
                   
                   
               
               
                 group 
                   
                   
                   
                   
                   
                   
               
               
                 (10 mg/kg, i.p; 
                   
                   
                   
                   
                   
                   
               
               
                 On day 1, 3, 6, 
                   
                   
                   
                   
                   
                   
               
               
                 9, 12, 18, 24, 
                   
                   
                   
                   
                   
                   
               
               
                 30 &amp; 33) 
                   
                   
                   
                   
                   
                   
               
               
                 C6481 mAb 
                 5 
                 25 
                 *(p &lt; 0.05) 
                  8 
                 ns 
                 −15 
               
               
                 group 
                   
                   
                   
                   
                   
                   
               
               
                 (10 mg/kg, 
                   
                   
                   
                   
                   
                   
               
               
                 i.p; On day 1, 
                   
                   
                   
                   
                   
                   
               
               
                 3, 6, 9, 12, 18, 
                   
                   
                   
                   
                   
                   
               
               
                 24, 30 &amp; 33) 
               
               
                   
               
               
                 TGI—Tumor growth inhibition (TGI was calculated against vehicle control IgG1 group) 
               
               
                 BWC—Body weight change 
               
               
                 ***p &lt; 0.001, *p &lt; 0.05 statistically significant when respective treatment groups were compared to vehicle control IgG1 group. 
               
               
                 ns Statistically non-significant when respective treatment groups were compared to vehicle control IgG1 group. 
               
            
           
         
       
     
     Tumor Volume (TV) &amp; Delta Tumor Volume (ΔTV) on Day 24 and Day 36 
     On day 24, the mean Tumor volume (mm3) for C5511 mAb group, Vehicle control IgG1 group, &amp; C6481 mAb group were 241±31, 474±38, and 355±68, respectively. Further the mean delta tumor volume (ΔTV) on day 24 for C5511 mAb group, vehicle control IgG1 group, &amp; C6481 mAb groups were 204±32, 437±38, and 318±68 mm3, respectively. The treatment groups, C5511 mAb group and C6481 mAb group showed significant decrease (p&lt;0.001 &amp; p&lt;0.05) in the tumor volume and delta tumor volume when compared to Vehicle control IgG1 group on day 24. The mean tumor volume on day 36 for C5511 mAb group, vehicle control IgG1 group, and C6481 mAb group were 690±186, 1062±157, and 977±230 mm3 respectively. The mean delta tumor volume (ΔTV) on day 36 for C5511 mAb group, vehicle control IgG1 group, and C6481 mAb groups were 654±187, 1025±159, and 940±231 mm3 respectively. The treatment groups, C5511 mAb group showed significant decrease (p&lt;0.05) in the tumor volume and delta tumor volume when compared to vehicle control IgG1 group. The results of tumor volume (TV) &amp; Delta tumor volume (ΔTV) for all treatment groups are summarized in table 44 and 45, and  FIGS. 20D, 20E, 20F and 20G . 
     
       
         
           
               
             
               
                 TABLE 44 
               
             
            
               
                   
               
               
                 Effect of test compounds on mean tumor volume of (huNOG-EXL)  
               
               
                 mice bearing subcutaneous PC-3 tumor xenograft 
               
            
           
           
               
               
            
               
                   
                 Mean Tumor volume (mm 3 ) 
               
            
           
           
               
               
               
            
               
                   
                   
                 Days 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
            
               
                 Groups 
                   
                 1 
                 3 
                 6 
                 9 
                 12 
                 15 
                 18 
                 21 
                 24 
                 27 
                 30 
                 33 
                 36 
               
               
                   
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
            
               
                 C5511 
                 Mean 
                 37 
                 58 
                 78 
                 97 
                 112 
                 152 
                 179 
                 213 
                 241 
                 356 
                 508 
                 621 
                 690 
               
               
                 mAb 
                 S.E.M 
                 1 
                 3 
                 4 
                 6 
                 2 
                 12 
                 39 
                 31 
                 31 
                 60 
                 95 
                 143 
                 186 
               
               
                 group 
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 (10 mg/kg, 
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 i.p; On 
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 day 1, 3, 
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 6, 9, 12, 
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 18, 24, 30 
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 &amp; 33) 
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 Vehicle 
                 Mean 
                 37 
                 61 
                 94 
                 114 
                 131 
                 190 
                 270 
                 363 
                 474 
                 569 
                 727 
                 894 
                 1062 
               
               
                 control 
                 S.E.M 
                 1 
                 2 
                 4 
                 7 
                 11 
                 12 
                 25 
                 32 
                 38 
                 38 
                 69 
                 83 
                 157 
               
               
                 IgG1 
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 group (10 
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 mg/kg, i.p; 
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 On day 1, 
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 3, 6, 9, 12, 
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 18, 24, 30 
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 &amp; 33) 
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 C6481 
                 Mean 
                 39 
                 54 
                 79 
                 101 
                 121 
                 166 
                 207 
                 288 
                 355 
                 456 
                 587 
                 734 
                 977 
               
               
                 mAb 
                 S.E.M 
                 2 
                 2 
                 6 
                 11 
                 15 
                 21 
                 33 
                 60 
                 68 
                 102 
                 108 
                 125 
                 230 
               
               
                 group 
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 (10 mg/kg, 
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 i.p; On 
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 day 1, 3, 
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 6, 9, 12, 
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 18, 24, 30 
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 &amp; 33) 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 45 
               
             
            
               
                   
               
               
                 Effect of test compounds on Δ (Delta) mean tumor volume of (huNOG-EXL) mice 
               
               
                 bearing subcutaneous PC-3 tumor xenograft  
               
            
           
           
               
               
            
               
                   
                 Δ (Delta) Mean Tumor Volume (mm 3 ) 
               
            
           
           
               
               
               
            
               
                   
                   
                 Days 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
            
               
                 Groups 
                   
                 1 
                 3 
                 6 
                 9 
                 12 
                 15 
                 18 
                 21 
                 24 
                 27 
                 30 
                 33 
                 36 
               
               
                   
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
            
               
                 C5511 mAb group 
                 Mean 
                 0 
                 20 
                 41 
                 60 
                 75 
                 115 
                 142 
                 176 
                 204 
                 320 
                 473 
                 585 
                 654 
               
               
                 (10 mg/kg, i.p; On 
                 S.E.M 
                 0 
                 3 
                 4 
                 5 
                 2 
                 12 
                 39 
                 32 
                 32 
                 61 
                 97 
                 145 
                 187 
               
               
                 day 1, 3, 6, 9, 12, 
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 18, 24, 30 &amp; 33) 
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 Vehicle control 
                 Mean 
                 0 
                 24 
                 56 
                 77 
                 94 
                 153 
                 233 
                 326 
                 437 
                 531 
                 689 
                 856 
                 1025 
               
               
                 IgG1 group (10 
                 S.E.M 
                 0 
                 2 
                 4 
                 7 
                 11 
                 13 
                 25 
                 33 
                 38 
                 39 
                 70 
                 83 
                 159 
               
               
                 mg/kg, i.p; On day 
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 1, 3, 6, 9, 12, 18, 
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 24, 30 &amp; 33) 
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 C6481 mAb group 
                 Mean 
                 0 
                 15 
                 42 
                 64 
                 83 
                 129 
                 170 
                 250 
                 318 
                 419 
                 550 
                 697 
                 940 
               
               
                 (10 mg/kg, i.p; On 
                 S.E.M 
                 0 
                 1 
                 5 
                 11 
                 15 
                 21 
                 33 
                 60 
                 68 
                 102 
                 108 
                 125 
                 231 
               
               
                 day 1, 3, 6, 9, 12, 
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 18, 24, 30 &amp; 33) 
               
               
                   
               
            
           
         
       
     
     Percentage Tumor Growth Inhibition (% TGI) on Day 24 and Day 36 
     The % Tumor Growth Inhibition (% TGI) for C5511 mAb group showed maximum value of 49% followed by C6481 mAb group with % TGI value of 25%, on day 24. Whereas, the % TGI on day 36, values for C5511 mAb group, and C6481 mAb groups were 35%, and 8% respectively on day 36 against Vehicle control IgG1 group. The individual animal Tumor Growth Inhibition are summarized in Table 46. 
     
       
         
           
               
             
               
                 TABLE 46 
               
             
            
               
                   
               
               
                 % Tumor growth inhibition (% TGI) of test compounds against 
               
               
                 (huNOG-EXL) mice bearing PC-3 tumor xenograft  
               
            
           
           
               
               
               
               
               
            
               
                   
                   
                   
                   
                 % Tumor growth inhibition (% TGI) by Delta 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
               
               
               
            
               
                   
                 Day 
                 Day 
                 Day 
                 Day 
                 Day 
                 Day 
                 Day 
                 Day 
                 Day 
                 Day 
                 Day 
                 Day 
                 Day 
               
               
                 Groups 
                 1 
                 3 
                 6 
                 9 
                 12 
                 15 
                 18 
                 21 
                 24 
                 27 
                 30 
                 33 
                 36 
               
               
                   
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
               
               
               
            
               
                 C5511 mAb group 
                 0 
                 6 
                 17 
                 15 
                 14 
                 20 
                 34 
                 41 
                 49 
                 37 
                 30 
                 31 
                 35 
               
               
                 (10 mg/kg, i.p; On day 1, 
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 3, 6, 9, 12, 18, 24, 30 &amp; 
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 33) 
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 Vehicle Control IgG1 
                 −1 
                 3 
                 6 
                 9 
                 12 
                 17 
                 25 
                 5 
                 15 
                 16 
                 9 
                 8 
                 2 
               
               
                 group 
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 P3E (10 mg/kg, i.p; On 
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 day 1, 3, 6, 9, 12, 18, 24, 
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 30 &amp; 33) 
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 C6481 mAb group 
                 −4 
                 12 
                 16 
                 11 
                 8 
                 13 
                 24 
                 21 
                 25 
                 20 
                 19 
                 18 
                 8 
               
               
                 (10 mg/kg, i.p; On day 1, 
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 3, 6, 9, 12, 18, 24, 30 &amp; 
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 33) 
               
               
                   
               
            
           
         
       
     
     Relative Tumor Volume (RTV) &amp; Delta Relative Tumor Volume (ΔRTV) on Day 24 and Day 36 
     On day 24, the mean relative tumor volume for C5511 mAb group vehicle control IgG1 group, and C6481 mAb group were 7±1, 13±1, and 10±2 respectively. The delta relative tumor volume (ΔRTV) for C5511 mAb group, vehicle control IgG1 group, and C6481 mAb group were 6±1, 12±1, and 9±2 respectively as shown in table 5. The treatment groups, C5511 mAb group showed significant decrease (p&lt;0.001) in the relative tumor volume and delta relative tumor volume when compared to vehicle control IgG1 group  FIGS. 20H and 20I . The mean relative tumor volume on day 36, 20±6 in C5511 mAb group, 29±5 in vehicle control IgG1 group, and 27±7 in C6481 mAb group. Whereas on day 36, the mean delta tumor volume (ΔRTV) for C5511 mAb group, vehicle control IgG1 group and C6481 mAb groups were 19±6, 28±5, and 26±7 respectively as shown in Table 47 and  FIGS. 20J and 20K . 
     
       
         
           
               
             
               
                 TABLE 47 
               
             
            
               
                   
               
               
                 Relative tumor volume (RTV) of test compounds against  
               
               
                 (huNOG-EXL) mice bearing PC-3 tumor xenograft  
               
            
           
           
               
               
            
               
                   
                 Relative Tumor Volume (mm 3 ) 
               
            
           
           
               
               
               
            
               
                   
                   
                 Days 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
            
               
                   
                   
                 Day 
                 Day 
                 Day 
                 Day 
                 Day 
                 Day 
                 Day 
                 Day 
                 Day 
                 Day 
                 Day 
                 Day 
                 Day 
               
               
                 Groups 
                   
                 1 
                 3 
                 6 
                 9 
                 12 
                 15 
                 18 
                 21 
                 24 
                 27 
                 30 
                 33 
                 36 
               
               
                   
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
            
               
                 C5511 mAb group 
                 Mean 
                 1 
                 2 
                 2 
                 3 
                 3 
                 4 
                 5 
                 6 
                 7 
                 10 
                 15 
                 18 
                 20 
               
               
                 (10 mg/kg, i.p; On 
                 S.E.M 
                 0 
                 0 
                 0 
                 0 
                 0 
                 0 
                 1 
                 1 
                 1 
                 2 
                 3 
                 5 
                 6 
               
               
                 day 1, 3, 6, 9, 12, 
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 18, 24, 30 &amp; 33) 
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 Vehicle control 
                 Mean 
                 1 
                 2 
                 3 
                 3 
                 4 
                 5 
                 7 
                 10 
                 13 
                 15 
                 20 
                 24 
                 29 
               
               
                 IgG1 group 
                 S.E.M 
                 0 
                 0 
                 0 
                 0 
                 0 
                 0 
                 1 
                 1 
                 1 
                 1 
                 2 
                 3 
                 5 
               
               
                 (10 mg/kg, i.p; On 
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 day 1, 3, 6, 9, 12, 
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 18, 24, 30 &amp; 33) 
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 C6481 mAb group 
                 Mean 
                 1 
                 1 
                 2 
                 3 
                 3 
                 4 
                 6 
                 8 
                 10 
                 12 
                 16 
                 20 
                 27 
               
               
                 (10 mg/kg, i.p; On 
                 S.E.M 
                 0 
                 0 
                 0 
                 0 
                 0 
                 1 
                 1 
                 2 
                 2 
                 3 
                 3 
                 4 
                 7 
               
               
                 day 1, 3, 6, 9, 12, 
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 18, 24, 30 &amp; 33) 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 48 
               
             
            
               
                   
               
               
                 Delta relative tumor volume (ΔRTV) of test compounds against  
               
               
                 (huNOG-EXL) mice bearing PC-3 tumor xenograft  
               
            
           
           
               
               
            
               
                   
                 Delta Relative Tumor Volume (mm 3 ) 
               
            
           
           
               
               
               
            
               
                   
                   
                 Days 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
            
               
                   
                   
                 Day 
                 Day 
                 Day 
                 Day 
                 Day 
                 Day 
                 Day 
                 Day 
                 Day 
                 Day 
                 Day 
                 Day 
                 Day 
               
               
                 Groups 
                   
                 1 
                 3 
                 6 
                 9 
                 12 
                 15 
                 18 
                 21 
                 24 
                 27 
                 30 
                 33 
                 36 
               
               
                   
               
            
           
           
               
               
               
               
               
               
               
               
               
               
               
               
               
               
               
            
               
                 C5511 mAb group 
                 Mean 
                 0 
                 1 
                 1 
                 2 
                 2 
                 3 
                 4 
                 5 
                 6 
                 9 
                 14 
                 17 
                 19 
               
               
                 (10 mg/kg, i.p; On 
                 S.E.M 
                 0 
                 0 
                 0 
                 0 
                 0 
                 0 
                 1 
                 1 
                 1 
                 2 
                 3 
                 5 
                 6 
               
               
                 day 1, 3, 6, 9, 12, 18, 
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 24, 30 &amp; 33) 
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 Vehicle control IgG1 
                 Mean 
                 0 
                 1 
                 2 
                 2 
                 3 
                 4 
                 6 
                 9 
                 12 
                 14 
                 19 
                 23 
                 28 
               
               
                 group (10 mg/kg, 
                 S.E.M 
                 0 
                 0 
                 0 
                 0 
                 0 
                 0 
                 1 
                 1 
                 1 
                 1 
                 2 
                 3 
                 5 
               
               
                 i.p; On day 1, 3, 6, 9, 
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 12, 18, 24, 30 &amp; 33) 
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 C6481 mAb group 
                 Mean 
                 0 
                 0 
                 1 
                 2 
                 2 
                 3 
                 5 
                 7 
                 9 
                 11 
                 15 
                 19 
                 26 
               
               
                 (10 mg/kg, i.p; On 
                 S.E.M 
                 0 
                 0 
                 0 
                 0 
                 0 
                 1 
                 1 
                 2 
                 2 
                 3 
                 3 
                 4 
                 7 
               
               
                 day 1, 3, 6, 9, 12, 18, 
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 24, 30 &amp; 33) 
               
               
                   
               
            
           
         
       
     
     The study revealed, under the test conditions, test compounds used in C5511 mAb group, vehicle control IgG1 group and C6481 mAb group at a dose of 10 mg/kg intraperitoneally (on day 1, 3, 6, 9, 12, 18, 24, 30 &amp; 33) were tested to evaluate the anticancer efficacy against PC-3 tumor xenograft in huNOG-EXL mice. Efficacy evaluation was calculated against vehicle control IgG1 group. Among tested compounds, C5511 mAb group and C6481 mAb group exhibited significant anti-cancer efficacy when compared with vehicle control IgG1 group. Based on statistical analysis of tumor volume, tumor growth inhibition, relative tumor volume, treatment with C5511 mAb group showed better antitumor efficacy compared to test compound used in C6481 mAb group. Moderate body weight loss observed in all the treatment groups. 
     In this context, it should be noted that the monoclonal antibody products tested in current HuNOG study, were utilized under sub optimal assay condition. The monoclonal antibody products used in this study require human NK cells for optimal function and till date no animal model is available where human NK cells could mimic the in vivo condition. Considering these constrains, HuNOG model was used rationally, wherein the human immune cells (including human NK cells) are established in mouse. However, the abundance of NK cells are significantly low. Therefore HuNOG mice model is justifiably provides a suitable experimental condition to test these novel Anti-CLEC2D monoclonal antibody products. Moreover, it was observed that the overall number of human immune cells start to decline, as the animals become older, with progression of the study. These levels of tumor growth reduction in the HuNOG PC3 xenograft model is surprising, indicating highly superior efficacy of the novel Anti-CLEC2D monoclonal antibodies of the present disclosure. 
     Example 8: Characterization of Anti-CLEC2D Monoclonal Antibody 
     Purified anti-CLEC2D antibody was subjected various biophysical and biochemical characterization indicative of multiple inherent properties of antibody such as, mass, conformation, posttranslational modification, amongst others. 
     In order to identify the confirmation of isolated fragments, SDS PAGE was carried out 
                     TABLE 49                  intact mass analysis                                     Sr. No.   Mass (Da)   Intensity (Counts)   Intensity (%)                                                 1   149301   252629056   100           2   149131   228375856   90.4           3   149302   227410624   90.02           4   149132   222516864   88.08           5   149300   217502800   86.1           6   149466   200116976   79.21           7   149465   198714320   78.66           8   149130   186866464   73.97           9   149133   183556800   72.66           10   149303   170258512   67.39                        
under non-reducing conditions, where a single major band corresponding to a molecular weight (MW) of 150 kDa was observed for all the samples indicating the intact anti-CLEC2D antibody. While under reducing conditions, two bands were evident at 25 kDa and 50 kDa which were associated with light chain and heavy chains of the anti-CLEC2D antibody. SDS PAGE data has been shown in  FIG. 21A ).
 
     The intact mass experiment was carried out using methods based on ELISA, flow cytometry, Western blotting, BIACORE, Waters UPLC H-Class Bio with Xevo G2 XS QTOF with UNIFI. The Xevo G2 XS QTOF was run in positive sensitivity MS only mode. With no prior treatment, 1 μg sample was analyzed using the same chromatographic conditions (only gradient different from subunit mass analysis) and mass spectrometric conditions as subunit mass analysis as described above. 
     The most abundant masses are close to generic glycosylated IgG1 monoclonal antibody as shown in  FIG. 21B ), and Table 49, thus confirming the molecular weight of anti-CLEC2D monoclonal antibody. 
     Acidic, Basic and Main peak was resolved and the percentage of each variant along with main peak is tabulated in below shows the charge distribution determined by WCX-LC method in anti-CLEC2D antibody molecule. The relative abundance of acidic isoforms is generally attributed to oxidation, deamidation, and glycation process within the antibody. On the other hand, the presence of C-terminal Lysine and amidation are mainly responsible for forming basic isoforms in the antibody. The WCX chromatogram is shown in  FIG. 21C ). 
     Acidic Species: 10% 
     Main Species: 83% 
     Basic Species: 7% 
     It is known that protein aggregation can induce immunogenicity; although a small amount of aggregates is expected, this amount is likely to increase due to stress conditions that a antibody may undergo during its manufacture, purification, formulation, and shelf-life. Aggregation can also induce production of anti-drug antibodies (ADAs) which can result in the loss of activity or cause adverse effects upon administration. Anti-CLEC2D antibody sample was analyzed by size exclusion chromatography (SEC) and typical chromatograms were shown in below. As observed in attached chromatogram in  FIG. 21D ), 100% monomer was observed thus confirming that sample is free from any aggregates and/or degradant. 
     One of the important quality attribute for therapeutic monoclonal antibodies is their glycosylation profile. To check the glycan distributions of anti-CLEC2D antibody, the sample was analyzed by HILIC N-glycan profiling method. The major glycan such as G0F, G1F, G1F′ and G2F were identified and total percentage of Galactosylated glycan was found to be around 46.44%. 
     Binding Studies Against Soluble CLEC2D Antigen: 
     Binding studies were carried out using anti-CLEC2D antibody against purified soluble CLEC2D antigen while the measurements were made through both ELISA and SPR based methods. 
     Besides, SPR was also employed to understand the interaction between anti-CLEC2D antibody and FcRn, as Binding interactions with the neonatal Fc receptor (FcRn) are one determinant of pharmacokinetic properties of recombinant human monoclonal antibody therapeutics, and a conserved binding motif in the crystallizable fragment (Fc) region of IgG molecules interacts with FcRn. 
     ELISA: 
     Soluble CLEC2D antigen was produced and purified using CHO cell culture system and Anti-CLEC2D antibody C5511 were used for ELISA assay. The method was optimized using various ELISA formats, as exemplified by, direct ELISA, indirect ELISA and sandwich ELISA. Finally, the optimized ELISA assay was based on protein A coated plate wherein the antigen was labelled with biotin moiety. The Anti-CLEC2D antibody dilutions ranging from 0.01 μg/mL to 62.5 μg/mL were made in dilution buffer 0.5% BSA in (DPBS with 0.05% tween 20). 
     The protein A coated wells were washed thrice with 200 μL of wash buffer (DPBS with 0.1% Tween20). 100 μL of each antibody dilution was added to well, and the plate was incubated for 90 minutes at room temperature on orbital shaker. Each well was rinsed four times with 200 μL of wash buffer. 100 μL of different concentration of biotinylated antigen, labelling was carried out as described before, was added to each well and plate was incubated for 60 minutes at room temperature on orbital shaker. Each well was rinsed four times with 200 μL of wash buffer. 100 μL of 1:5000 diluted HRP-labelled streptavidin was added and plate was incubated for 60 minutes at room temperature on orbital shaker. Each well was rinsed five times with 200 μL of wash buffer. 100 μl 1×TMB was added and the plate was incubated for 30 min at RT in dark. After 30 minutes 100 μl of stop solution was added and the plate was read at 450 nm. 
     Further to appropriate subtraction of blank, absorbance values were plotted and fit into binding model based on sigmoidal association, using Graphpad PRISM 6.0. The KD value as obtained from the fit is found to be 10-17 nM for anti-CLEC2D antibody to purified CLEC2D antigen ( FIG. 21F ). The experiments were repeated at least 3 times independently in triplicates to achieve statistical confidence and variation was found to be less than 5%, while confidence interval resides within 95%. 
     BIAcore binding studies with anti-CLEC2D antibody against soluble CLEC2D antigen 
     CLEC2D antigen interaction with specific monoclonal antibody was monitored through surface plasmon resonance, using BIACORE. The kinetic parameters for the interaction of anti-CLEC2D antibodies with CLEC2D antigen were evaluated. This method was used to screen potential high affinity monoclonal antibodies against CLEC2D antigen. Different monoclonal antibodies revealed differential affinities towards the CLEC2D antigen. The experiment revealed affinity constants ranging from less than 100 nM (e.g., ≤90 nM, ≤80 nM, ≤70 nM, ≤60 nM, ≤50 nM, ≤40 nM, ≤30 nM, ≤20 nM, ≤10 nM, ≤5 nM, or ≤1 nM). 
     CLEC2D antigen binding kinetics and affinity studies between CLEC2D antigen and Anti-CLEC2D antibody binding studies were carried out using Anti-His Antibody binding capture chemistry on BIACORE 3000 instrument. His Capture Kit (GE healthcare) was immobilized onto CM5 chip surface at an RU of ˜1800. CLEC2D antigen was captured on Anti-His, coupled with CM5 chip, surface, at a concentration of ˜200 μg/mL, wherein the dilution of antigen was made through running buffer comprising HBS-EP+ buffer (GE healthcare). Subsequently anti-CLEC2D antibody C5511 was passed at concentrations ranging from 1 to 100 μg/mL, at association and dissociation time of 3 minutes and 25 minutes, respectively. Antibody dilutions were made in HBS-EP+ buffer (GE healthcare). Response curves ( FIG. 21G ) obtained were appropriately subtracted from reference flow cell signal and blanks, respectively and fit to a 1:1:1 Langmuir binding leading to estimated KD of ˜10 9 M−1. 
     FcRn Binding 
     Surface plasmon resonance (SPR) biosensor assays are often used to characterize interactions between FcRn and antibody therapeutics. Studies have shown that FcRn interacts with a binding motif in the crystallizable fragment (Fc) of IgG at the CH2-CH3 domain interface in a pH-dependent manner. 6,8 The pH dependency of this interaction is essential for maintaining the long serum half-life of IgG molecules. Specifically, in the endosomes of endothelial cells (˜pH 6.0), IgG internalized through pinocytosis binds to FcRn to form IgG-FcRn complexes; the IgG-FcRn complexes are then trafficked to the cell surface where IgG is released backcinto the circulation at physiological pH (˜7.4). This prevents lysosomal degradation of the IgG. For recombinant human monoclonal antibody (rhumAb) therapeutics, the FcRn-rhumAb binding interaction is a critical determinant of pharmacokinetic (PK) properties and targeted engineering of the FcRn binding motif may enable less frequent dosing of antibody therapeutics in patients. Multiple studies have suggested that there is a correlation between FcRn binding affinity and antibody half-life, although the absence of such a correlation has also been reported. 
     Binding kinetics and affinity studies between Human FcRn/FCGRT &amp; B2M Heterodimer Protein and Anti-CLEC2D antibody binding studies were carried out using BIACORE 3000 instrument. Human FcRn/FCGRT &amp; B2M Heterodimer Protein (Acro Biosystems) was immobilized onto CM5 chip surface at an RU of ˜300. Human FcRn/FCGRT &amp; B2M Heterodimer Protein was captured on CM5 chip surface through amine coupling, at a concentration of ˜1 μg/mL, wherein the dilution of protein was made through running buffer comprising HBS-EP+ buffer (GE healthcare). Subsequently anti-CLEC2D antibody C5511 was passed at concentrations ranging from 0.0315 to 0.5 μM, at both pH 5.9 and pH 7.4. Antibody dilutions were made in HBS-EP+ buffer (GE healthcare). As can be seen from the response curve that there was no binding observed at pH 7.4 ( FIG. 21H ) while response was monitored at pH 5.9 ( FIG. 21I ). Response curves obtained were appropriately subtracted from reference flow cell signal and blanks, respectively and fit to a 1:1:1 Langmuir binding leading to estimated KD of ˜1.88×10 6  M−1. As can be concluded that no binding at neutral pH may increase the possibility of the anti-CLEC2D antibody to be released back into the blood stream. 
     Example 9: Anti-CLEC2D Monoclonal Antibody as a Diagnostic Tool/as Prognostic Marker Against Multiple Disease Indications 
     All high binding anti-CLEC2D antibodies were screened to pick the top binder as diagnostic antibody. Among the 4 high binding anti-CLEC2D antibody, one was selected through antigen binding assay with PC3 tumor cell line. 
     Tumor cells expressing CLEC2D antigen were harvested by trypsinization. Cell count was taken by Vi-cell XR automated cell counter. Cells were centrifuged at 1400-1500 rpm for 4-5 minutes. The pellet was re-suspended in 1 ml DPBS. 50,000 cells were aliquoted in each well of a 96 well plate. 1 μg of C2779, C2438, C0949, C2543 were added to each well and incubated for 30-60 minutes at room temperature (25° C.). The plate was centrifuged at 1400-1500 rpm for 4-5 minutes, the supernatant was aspirated and cells were washed with 0.1% BSA in DPBS. 2.5 ml of 2% BSA was diluted to 50 ml with DPBS. Goat anti human IgG FITC conjugate was used as secondary antibody. 1:100 dilution of secondary antibody was prepared in DPBS and 100 μl was added to each well. The secondary antibody, Goat anti human IgG FITC conjugate, was used as control at 1:100 dilution for all relevant experimentation. The plate was incubated for 30 minutes at room temperature (25° C.) in dark. The cells were washed with 0.1% BSA and re-suspended in 100 μl of 1% BSA. Samples were analyzed by flow-cytometry. 
     C0949 was selected as diagnostic antibody reagent due to maximum percentage of binding observed against surface expressed CLEC2D on PC3 when compared with other anti-CLEC2D clones ( FIG. 22A ) and purposed further to detect CLEC2D antigen on various tumour cell lines. 
     Among the prostate cancer cell lines, 22RV showed highest antigen expression with 5 fold increase as compared to secondary antibody control ( FIG. 22B ). Further, diagnostic anti-CLEC2D antibody, not limited to C0949, was used in antigen binding assay for multiple tumor cell lines of several disease indications shown in  FIG. 22C . 
     Efficient and sensitive binding as observed in multiple cancer cell lines including prostate cancer cell lines, using various anti-CLEC2D antibody clones, strongly support the candidacy of the said molecules as diagnostic/prognostic reagent. 
     Clinical Prospect of Anti-CLEC2D Monoclonal Antibody 
     Disease relevance: prostate cancer 
     TCGA Analysis 
     The cancer genome atlas (TCGA) data was metastatic prostate cancer was analysed to improve on the current understanding of genes involved in the disease progression along with the expression level of CLEC2D in prostate cancer patients. 
     The PRAD project is the TCGA&#39;s prostate cancer project and it contains data for 500 Cancer cases. The relevant sources of data that were analysed were limited to Gene Expression Quantification, which included HTSeq Count Data, miRNA Expression Quantification and Isoform Expression Quantification. Table 50 shows a case-wise breakdown of the occurrences of the above specified files in the data that was accessible for download from the data categories of interest. 
     
       
         
           
               
             
               
                 TABLE 50 
               
             
            
               
                   
               
               
                 A breakdown of the cases based  
               
               
                 on the availability of different 
               
               
                 data files, such as tumor and normal files 
               
            
           
           
               
               
               
            
               
                 Description 
                 Cases 
                 Percentage 
               
            
           
           
               
            
               
                 Transcriptome Profiling 
               
               
                   
               
            
           
           
               
               
               
            
               
                 No files 
                 2 
                 0.4 
               
               
                 only miRNA + Isoform 
                 3 
                 0.6 
               
               
                 only GEQ 
                 4 
                 0.8 
               
               
                 all files, only Tumor 
                 436 
                 87.2 
               
               
                 all files, Tumor + Normal 
                 52 
                 10.4 
               
               
                 two different miRNA + Isoform Files 
                 1 
                 0.2 
               
               
                 two different GEQ (tumor) files 
                 2 
                 0.4 
               
               
                   
               
            
           
         
       
     
     TCGA Data—Transcriptome Profiling 
     The transcriptome profiling data category contains counts of gene, miRNA and isoform expression. Of the 500 cases deposited in the TCGA, 498 have data associated with Primary Tumor tissue, while 52 cases have expression data related to the Normal Tissue. The files are a list of 60483 genes and their variants, denoted by their Ensembl IDs and their counts within each case. 
     TCGA Data—Metastatic Cases Identification 
     The 500 TCGA PRAD Project cases were parsed to identify cases which displayed characteristics that would lead to them being identified as cases of metastatic prostate cancers. A total of 289 cases were identified to be metastatic, this identification was made on the basis of key parameters, in other TCGA documentation which lists among other parameters Gleason Scores and prescribed Drugs. Of the 289, only 18 had relevant Normal Tissue data, as this analysis is concerned with the change in expression levels for before and after the disease, it was necessary to establish baseline values, Normal data, for the other genes as well. This was achieved by looking at all 52 Normal Tissue data, these were used to create a baseline file, by taking into account all 52 values from each case for each gene, removing outlier values, and calculating an ‘normal baseline’ value for the gene. For cases lacking a Normal Tissue counts, the baseline file was used for the comparative analysis. 
     TCGA Data—Metastatic Cases Sub-Groupings 
     The same key parameters which served as the basis of the Metastatic case identification were also used to segregate the data into other sub-groupings such as stage of the cancer and current treatment regimen—this data was used to analyse the CLEC2D Expression levels among the sub-groups 
     Subsequently expression of CLEC2D gene was monitored wherein all the associated FPKM files from the projects were downloaded and specifically queried for CLEC2D expression. The FPKM files were made up of Tumor expression files and in some cases Normal Tissue Expression files. Both sets were separately used to calculate a range for CLEC2DCLEC2D Expression for each cancer among Normal and Tissue cases. Additionally outliers were omitted from the data by assuming a normal distribution of the Expression values and discarding values that were more than 2 standard deviations away from the mean. 
     In order to better understand the role of CLEC2D in cancers the relative expression levels of the gene in normal tissue samples and tumor tissue samples was analysed. This was done by collecting all the case data for specific cancers/conditions and retrieving the CLEC2D expression value from each file before analysing the sets of values. For each subset the ‘spread’ of the CLEC2D expression profile was plotted by looking at the minimum, maximum and interquartile values. As can be seen from  FIG. 23A , CLEC2D appears to conform remarkable existence in terms of expression level seen in different subsets conditions, such as, metastasis, tumor stage and treatment received, amongst others. 
     Induction Driven Expression Increase 
     In order to determine the expression label of CLEC2D on the surface of different tumor cell lines, firstly surface expression of CLEC2D on the surface of CLEC2D transfected HDCHO, C4548, was looked at and distribution of same was observed on the transfected cells by using commercially available anti-CLEC2D (4C7) antibody. Assuming translation of CLEC2D could be heavily regulated upon various kind of inductions, various prostate cancer cell types were induced with multiple inducers such as effector cells (either whole PBMC or supernatant of PBMC) or activators of NK cells (e.g., LPS) on prostate tumor cell line (PC3) to monitor the impact on expression label of CLEC2D. Upon treatments with various inducers, an increased CLEC2D expression label was observed when compared to the untreated target cells. 
     Among the prostate tumor cell lines under no induction, castrate-resistant prostate cancer (CRPC) cell lines i.e. PC3 and DU145 have high CLEC2D surface expression compare to Non-CRPC cell lines i.e. LNCap and 22RV1 wherein the CLEC2D was probed by using Novel anti-CLEC2D antibody as exemplified by, not limited to, C2685 clone ( FIG. 23B ). Extending the observation obtained in uninduced condition, the therapeutic anti-CLEC2D antibody, such as C2685, not limited to, was used to understand the changes in expression level in the presence or absence of inducers. Next, in order to look into the changes in expression label of CLEC2D on all prostate tumor cell lines upon various treatments, prostate tumor cells were incubated with effector cells (either whole PBMC or supernatant of PBMC or isolated NK cells or isolated T cells) or with activators/inducers of NK cells (either LPS or Poly I:C or IFN gamma), and examined the expression label of CLEC2D by using C2685 anti-CLEC2D antibody. Upon treatment an increased expression label of CLEC2D was observed when compared with the untreated target cells ( FIG. 23C ). Among the prostate tumor cell lines, castrate-resistant prostate cancer (CRPC) cell lines i.e. PC3 and Non-CRPC cell line i.e., LNCap have shown further enhancement of CLEC2D surface expression upon treatment compare to DU145 and 22RV1 treated with said inducers ( FIG. 23C ). 
     Considering all and having specific focus on prostate cancer, cell lines such as, castrate-resistant prostate cancer (CRPC) cell lines (such as PC3 and DU145) and Non-CRPC cell lines (such as LNCap and 22RV1), revealed significant expression level of CLEC2D antigen on tumor cell surface, which was further increased with various treatments, including multiple TLR treatments. The choice of cell lines were strategic, as all prostate cancer cell lines used herein signifies certain stage or condition of prostate cancer disease and can be associated with CLEC2D expression level. As described and shown in the present disclosure, prostate cancer cell lines, LNCaP, DU145, 22RV1 and PC3 have low, moderate and high metastatic potential wherein PC3, with high cell surface CLEC2D expression, is effectively killed by NK cells when the inhibitory signal through CLEC2D-CD161 axis is blocked using identified anti-CLEC2D antibody, thereby, establishing CLEC2D as clinically relevant target for prostate cancer. 
     Example 10: Expression of CLEC2D Antigen in Cancer Tissue 
     CLEC2D has been described as a multi-functional protein, and to fully elucidate the functional consequences of its interactions with its receptor, CD161, a comprehensive characterisation of CLEC2D distribution is needed. CLEC2D has been observed to be activated in different tumor cell lines and present on various immune cells in humans. CLEC2D can be detected in several healthy human tissues, and can be remarkably prevalent in immune-privileged sites. This information will be used to emphasize and postulate on the role of CLEC2D in cross talk between lymphocytes and immune tolerance. 
     The tissue microarray (TMA) represents a high-throughput technology for the assessment of histology-based laboratory tests, including immunohistochemistry and fluorescent in-situ hybridization (FISH). For immune-fluorescent staining, anti-CLEC2D monoclonal antibody is used as primary antibody and either direct labelling or indirect labelling, with a labelled secondary Ab, is used for detection. Thus, the role of CLEC2D is determined in various cancers and in the context of various stages of cancer. 
     Additionally, 3D cell culture methodology is used to understand the interaction of tissue expressed CLEC2D antigen with human immune system to determine the cross-talk between CLEC2D antigen and interacting partners (including CD161) expressing on tumor cells, and immune cell types, such as B cells, T cells, monocytes and NK cells. 
     Having described embodiments of this disclosure with reference to the accompanying drawings, it is to be understood that this disclosure is not limited to the precise embodiments, and that various changes and modifications may be effected therein by those skilled in the art without departing from the scope or spirit of this disclosure as defined in the appended claims. 
     Human tissue microarray from US Biomax (cat number TP242d), top 4 types of cancer (colon, breast, lung and prostate) tissue array with normal tissue, including TNM and pathology grade, 24cases/24 cores were used to analyse reactivity of anti-CLEC2D antibody clones C0694 and C2685. The prostate cancer samples are as follows. 
     
       
         
           
               
               
               
               
               
               
               
               
             
               
                 TABLE 51 
               
               
                   
               
               
                 Patient 
                 Patient 
                   
                 Pathology 
                   
                   
                   
                   
               
               
                 Age 
                 sex 
                 Cancer 
                 Diagnosis 
                 TNM 
                 Grade 
                 Stage 
                 Type 
               
               
                   
               
             
            
               
                 71 
                 M 
                 Prostate 
                 Adenocarcinoma 
                 T2N0M0 
                 1 
                 I 
                 Malignant 
               
               
                   
                   
                   
                 Gleason 2 (2 + 2) 
                   
                   
                   
                   
               
               
                 73 
                 M 
                 Prostate 
                 Adenocarcinoma 
                 T3N0M0 
                 2 
                 III 
                 Malignant 
               
               
                   
                   
                   
                 Gleason 4 (4 + 4) 
                   
                   
                   
                   
               
               
                 60 
                 M 
                 Prostate 
                 Adenocarcinoma 
                 T3N1M0 
                 2 
                 IV 
                 Malignant 
               
               
                   
                   
                   
                 Gleason 3 (3 + 3) 
                   
                   
                   
                   
               
               
                 64 
                 M 
                 Prostate 
                 Adenocarcinoma 
                 T3N0M0 
                 2 
                 III 
                 Malignant 
               
               
                   
                   
                   
                 Gleason 4 (4 + 3) 
                   
                   
                   
                   
               
               
                 31 
                 M 
                 Prostate 
                 Prostate tissue 
                 — 
                 — 
                 — 
                 Normal 
               
               
                 35 
                 M 
                 Prostate 
                 Prostate tissue 
                 — 
                 — 
                 — 
                 Normal 
               
               
                   
               
            
           
         
       
     
     The IHC staining followed both CC1 and CC2 protocols at different concentrations of antibody from 1:10 dilution to 1:30 dilution. The data suggests C2685 revealed strong reactivity and less interference from negative regions. Results are described in  FIG. 23D . 
     TCGA Data—all Cancers CLEC2D Expression 
     A pan-cancer analysis was carried out by studying all the TCGA cancer projects. All the associated FPKM files from the projects were downloaded and specifically queried for CLEC2D expression. The FPKM files were made up of Tumor expression files and in some cases Normal Tissue Expression files. Both sets were separately used to calculate a range for CLEC2D Expression for each cancer among Normal and Tissue cases. Additionally outliers were omitted from the data by assuming a normal distribution of the Expression values and discarding values that were more than 2 standard deviations away from the mean. 
     
       
         
           
               
             
               
                 TABLE 52 
               
               
                   
               
               
                 A List of the Cancers analysed for CLEC2D Expression. 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
            
               
                 ACC 
                 Adrenocortical Carcinoma 
               
               
                 BLCA 
                 Bladder Urothelial Carcinoma 
               
               
                 BRCA 
                 Breast Invasive Carcinoma 
               
               
                 CESC 
                 Cervical Squamous Cell Carcinoma and  
               
               
                   
                 Endocervical Adenocarcinoma 
               
               
                 CHOL 
                 Cholangiocarcinoma 
               
               
                 COAD 
                 Colon Adenocarcinoma 
               
               
                 DLBC* 
                 Lymphoid Neoplasm Diffuse Large B-cell Lymphoma 
               
               
                 ESCA 
                 Esophageal Carcinoma 
               
               
                 GBM 
                 Glioblastoma Multiforme 
               
               
                 HNSC 
                 Head and Neck Squamous Cell Carcinoma 
               
               
                 KICH 
                 Kidney Chromophobe 
               
               
                 KIRC 
                 Kidney Renal Clear Cell Carcinoma 
               
               
                 KIRP 
                 Kidney Renal Papillary Cell Carcinoma 
               
               
                 LAML 
                 Acute Myeloid Leukemia 
               
               
                 LGG 
                 Brain Lower Grade Glioma 
               
               
                 LIHC 
                 Liver Hepatocellular Carcinoma 
               
               
                 LUAD 
                 Lung Adenocarcinoma 
               
               
                 LUSC 
                 Lung Squamous Cell Carcinoma 
               
               
                 MESO 
                 Mesothelioma 
               
               
                 OV 
                 Ovarian Serous Cystadenocarcinoma 
               
               
                 PAAD* 
                 Pancreatic Adenocarcinoma 
               
               
                 PCPG 
                 Pheochromocytoma and Paraganglioma 
               
               
                 PRAD 
                 Prostate Adenocarcinoma 
               
               
                 READ 
                 Rectum Adenocarcinoma 
               
               
                 SARC 
                 Sarcoma 
               
               
                 SKCM 
                 Skin Cutaneous Melanoma 
               
               
                 STAD 
                 Stomach Adenocarcinoma 
               
               
                 TGCT* 
                 Testicular Germ Cell Tumors 
               
               
                 THCA 
                 Thyroid Carcinoma 
               
               
                 THYM* 
                 Thymoma 
               
               
                 UCEC 
                 Uterine Corpus Endometrial Carcinoma 
               
               
                 UCS 
                 Uterine Carcinosarcoma 
               
               
                 UVM 
                 Uveal Melanoma 
               
               
                   
               
               
                 *denotes projects whose CLEC2D expression levels differed significantly from the rest. 
               
            
           
         
       
     
     For each subset the ‘spread’ of the CLEC2D expression profile was plotted by looking at the minimum, maximum and interquartile values. As can be seen from  FIG. 24A  CLEC2D appears to conform remarkable existence in terms of expression level seen in different cancer conditions as listed in above table, amongst others. 
     Binding Studies: Flow Cytometry and Imaging 
     As observed in prostate cancer cell lines, the observations were extended to other tumour cell lines as well, using identified anti-CLEC2D antibody clones, as exemplified by C2685, C5511, amongst others. The binding was also monitored through both flow cytometry and confocal microscopy, wherein respective experimental conditions are similar to the description above. 
     Using anti-CLEC2D antibody C5511, flow cytometric observation have been summarized in the following Table 53. 
     
       
         
           
               
             
               
                 TABLE 53 
               
             
            
               
                   
               
               
                 Bispecific antibody 
               
            
           
           
               
               
               
               
            
               
                   
                   
                   
                 Binding fold  
               
               
                   
                   
                   
                 change against 
               
               
                   
                 Tumor  
                   
                 Control 
               
               
                   
                 cell line 
                 Disease indication 
                 (C5511) 
               
               
                   
                   
               
            
           
           
               
               
               
               
            
               
                   
                 HepG2 
                 Liver cancer 
                 1.5 
               
               
                   
                 SKBR3 
                 Breast cancer 
                 1.8 
               
               
                   
                 SKOV3 
                 Ovary cancer 
                 1.2 
               
               
                   
                 BT474 
                 Breast cancer 
                 2.0 
               
               
                   
                 Ramos 
                 Lymphoma 
                 2.2 
               
               
                   
                 FADu 
                 Head &amp; Neck  
                 1.2 
               
               
                   
                   
                 squamous cell carcinoma 
                   
               
               
                   
                 LN229 
                 Glioblastoma 
                 7.5 
               
               
                   
                 SW620 
                 Colon cancer 
                 2.3 
               
               
                   
                 MDA-MB-361 
                 Breast cancer 
                 3 
               
               
                   
                 NCI-H1838 
                 non-small cell lung cancer 
                 2.3 
               
               
                   
                 Capan-1 
                 Pancreatic cancer 
                 1.8 
               
               
                   
                   
               
            
           
         
       
     
     As can be understood, the expression level of CLEC2D on various cancer cell lines was found to be either low or moderate to high. 
     Similarly, in order to determine the disease relevance for novel antibodies we have checked the expression label of CLEC2D on the surface of different tumor cell lines such as liver carcinoma cancer, Glioma, ovarian adenocarcinoma, lung carcinoma, myeloma, lymphoma and breast cancer tough confocal microscopy. There are varying labels of expression of CLEC2D observed across the cancer cell lines tested by using anti-CLEC2D antibody clone C2685 ( FIG. 24B ). Predominant expression of CLEC2D was observed on the surface of hepatocellular carcinoma (HepG2), breast cancer (BT474), and glioma (LN229) whereas a very low or no expression observed in ovarian adenocarcinoma (SkoV3), myeloma (NCI-H929) and lymphoma (Ramos) ( FIG. 24B ). 
     To check the regulation on the translation of CLEC2D in these cancer cell lines were induced with various inducers such as effector cells (either whole PBMC or soup of PBMC) or activator of NK cells (e.g. LPS), IFN-γ, poly I:C to all tumor cell lines (HepG2, BT474, LN229, SkoV3, NCI-H929 and Ramos) similar to prostate tumor cell line and monitored expression label of CLEC2D. Upon treatments, increased expression label of CLEC2D was observed when compared to the untreated target cells ( FIG. 24C ). Interestingly, on the SkoV3, NCI-H929 and Ramos cells have observed increased expression of CLEC2D upon treatment whereas on untreated cells have no/less expression ( FIG. 24C ). These finding indicates that CLEC2D is induced upon specific TLR stimulations on these cells and could be a potential target on these cancer conditions which can be targeted using anti-CLEC2D antibody. 
     Cytotoxicity 
     Tumour cell lines, as exemplified by SKOV3 (Ovarrian cancer cell line), HepG2 (hepatocellular carcinoma) cells were labelled with Efluor as per the manufacturer&#39;s protocol and were seeded at a density of 0.04×10 6  in 20% DMEM in 24 well plates. After 24 hours, freshly isolated PBMCs were added in T:E of 1:5. Novel monoclonal anti-CLEC2D antibodies C5511 were added at 200 μg/ml in the assay reaction of 0.5 ml and incubated for 14 hours. Supernatant was collected from 24 well plate and adherent cells were trypsinized and collected in 1.5 ml tubes. Reaction mixture was incubated with sytox green (15 nM) for 20 min and fluorescence was detected in flow cytometer. Percent specific cell death was determined by subtracting the percent cell death of control from the test samples and showed significant cytotoxicity in ovarian (SKOv3) and liver (HepG2) ( FIG. 24D ) cancer cell lines indicating antitumor activity of anti-CLEC2D antibody against multiple diseases. 
     As can be understood, isolated anti-CLEC2D antibody that were used to monitor CLEC2D surface expression on several cell lines associated with diseases, such as breast cancer (BT474), lymphoma (ramos), liver cancer (HepG2), prostate cancer (PC3, DU145, LNCAP and 22RV1) glioma (LN229) ovarian adenocarcinoma (SkoV3), myeloma (NCI-H929), is first-in-class in the space. Moreover, cytotoxicity elicited by the said anti-CLEC2D antibody reflects the fact that these anti-CLEC2D antibody could be potentially used as therapeutic avenue against respective diseases. Taken together, this also signifies that CLEC2D antigen expression is linked with multiple cancer cell lines and could play an important role in cancer biology, as speculated the present disclosure. 
     Risk Mitigation Studies Done with Anti-CLEC2D Monoclonal Antibody 
     Immunogenicity to protein based biotherapeutics is a complex process involving numerous factors specific to products, including critical feature such as quality of drug, and patients. These critical quality attributes may include: variations in the primary sequence, host-cell specific post-translational modifications, the presence of host cell proteins, formulation changes, aggregation, chemical modifications (oxidation, deamidation, or glycation), and changes in protein structure. Some critical quality attributes of antibody drug products have been suggested to affect patient safety through enhancing the sequence based risk of immunogenicity, although the exact contribution of specific types of attributes is not known. T-cell dependent responses are the primary drivers of the long-term affinity matured immune response to biologics in the clinic. These include assay systems using: whole blood, peripheral blood mononuclear cells (PBMC), CD8+-depleted PBMC, immortalized cell lines, dendritic cells/monocytes/macrophages co-cultured with autologous CD4+ Tcells, and artificial lymph node systems, to name a few. Various biological outcomes can be measured at different stages of immune cell activation in these in vitro assays including, cytokine secretion, expression of cell surface markers of activation, identification of HLA-DR bound peptides, signal transduction events, phagocytosis by antigen presenting cells (APC), and proliferation. The application of the designated assay to the development of biopharmaceuticals can range from candidate selection at the early development phase to the late stage evaluation of specific attributes that may impact the risk of immunogenicity. Present disclosure details on attempts to evaluate anti-CLEC2D antibody associated risk towards immunogenicity or related attributes. 
     Lymphocyte Proliferation Studies 
     Proliferation of lymphocytes were tested by three independent experimental protocols such as, wet coating of antibodies, air dried coating of antibodies and high density PBMC pre-culture followed by induction with test antibodies, detailed as follows: 
     Wet Coating of Antibodies 
     Different concentrations of test antibodies, not limited to C5511, ranging from 1 μg/ml to 100 μg/ml and 1 μg/ml of the positive control—anti CD3 antibody, anti OKT3 antibody, were added to the wells of a 96 well flat bottom plate and incubated in a 37° C. incubator for 2-3 hours. After that the wells were washed three times with 200 μl of DPBS. PBMCs were labelled with Efluor 670 viable cell dye as per manufacturer&#39;s protocol. 30000 PBMC cells were seeded in each well in total 200 μl growth media (RPMI-1640 with 10% FBS). Day 0 samples were collected and analyzed by flow-cytometry. Cells were incubated at 37° C. in a 5% CO2 incubator for 4 days. On 4th day samples were collected, stained with anti CD4 antibody-FITC conjugate and analyzed by flow-cytometry. 
     Air Dried Coating of Antibodies 
     Different concentrations of test antibodies ranging from 1 μg/ml to 100 μg/ml and 1 μg/ml of the positive control anti CD3 antibody OKT3 were added to the wells of a 96 well flat bottom plate and air dried in biosafety cabinet. Volume of antibodies were restricted to less than 50 μl for optimum air drying. PBMCs were labelled with Efluor 670 viable cell dye as per manufacturer&#39;s protocol. Once the wells were dry, 30000 PBMC cells were seeded in each well in total 200 μl growth media (RPMI-1640 with 10% FBS). Day 0 samples were collected and analyzed by flow-cytometry. Cells were incubated at 37° C. in a 5% CO2 incubator for 4 days. On 4th day samples were collected, stained with anti CD4 antibody-FITC conjugate and analyzed by flow-cytometry. 
     High Density Pre-Culture of PBMC for TCR Priming Followed by Induction with Antibodies in Solution 
     PBMC cells were pre-cultured at 1×10{circumflex over ( )}6 cells/ml and 10×10{circumflex over ( )}6 cells/ml density for 48 hrs in growth media at 37° C. in a 5% CO2 incubator. After 48 hours PBMCs were labelled with Efluor 670 viable cell dye as per manufacturer&#39;s protocol. 1×10{circumflex over ( )}6 PBMC cells/ml were seeded in each well in total 200 μl growth media (RPMI-1640 with 10% FBS). Different concentrations of test antibodies ranging from 1 μg/ml to 100 μg/ml and 1 μg/ml of the positive control anti CD3 antibody OKT3 were added to the wells containing PBMCs. Day 0 samples were collected and analyzed by flow-cytometry. Cells were incubated at 37° C. in a 5% CO2 incubator for 4 days. On 4th day samples were collected, stained with anti CD4 antibody-FITC conjugate and analyzed by flow-cytometry. 
     Sample Processing for Flow-Cytometry 
     PBMC samples were centrifuged at 200 rpm for 5 minutes. Supernatants were discarded and the cells were re-suspended in 100 μl of DPBS with 0.5% BSA along with anti CD4 antibody-FITC conjugate (1:100 dilution in final reaction). Cells were incubated for 30 minutes in dark. After that cells were centrifuged at 200 rpm for 5 minutes, removed the supernatant and re-suspended in 100 μl of DPBS with 0.5% BSA. 
     As can be observed from  FIGS. 25A, 25B and 25C , wherein anti-CLEC2D antibody treatment was used as positive control, PBMC treated with anti OKT3 antibody showed lymphocyte proliferation as observed by partitioning of Efluor viability dye into multiple daughter populations (showed by the arrows on the histogram). Appearance of single population after 4 days of culture was observed in untreated PBMC control and 1 μg/ml to 100 μg/ml anti-CLEC2D antibody treated test samples, shows that anti-CLEC2D antibodies did not induce any lymphocyte proliferation. This observation was consistent with three independent test protocols that are wet coating of antibodies ( FIG. 25A ), air dried coating of antibodies ( FIG. 25B ) and high density PBMC pre-culture ( FIG. 25C ) followed by induction with test antibodies. PBMC from multiple healthy donors were tested and the results obtained were consistent. 
     Measurement of Secreted Cytokines: IFN-γ and IL2 
     As described earlier in the current segment, apart from understanding lymphocyte proliferation assay, it is essential to confirm whether Anti-CLEC2D antibody induces any cytokines, such as IFN-γ, IL2, or not. Measurement of secreted cytokines such as IFN-γ, IL2, not limited to, were performed through ELISA based detection method wherein supernatant collected from various experimental set up/conditions as detailed above e.g., high density, wet coating, was used at 24 hrs interval for subsequent quantitation. In all experiments concentration of respective antibodies used are anti OKT3 antibody (1 ug/ml) and anti-CLEC2D antibody clones such as C5511 C6481 C4608 at 100 ug/ml. Subsequently, supernatant obtained from anti OKT3 antibody treated sample was diluted in the ratio of 1:4 wherein 50 ul of supernatant was diluted by adding 150 ul of 10% RPMI 1640, on the contrary, anti-CLEC2D antibody treated samples were used directly without any further dilution of supernatant. Simultaneously, samples to measure cytokine IL2 was prepared by wet coating method. Herein anti OKT3 antibody treated sample was diluted in the ratio of 1:10 while 25 ul was diluted by adding 225 ul of 10% RPMI 1640, while supernatant collected from anti-CLEC2D antibody treated samples were used directly. Supernatant obtained from PBMC without treatment was used as control against respective experimentation either for IFN-γ or IL2. 
     As can be seen from  FIG. 25D , wherein PBMC treated with anti OKT3 antibody exhibited highest level of IFN gamma secretion in supernatant at a concentration of 1155 pg/mL while tested anti-CLEC2D antibodies did not elevate IFN gamma production beyond 30 pg/mL concentration, related to any anti-CLEC2D antibody clones ( FIG. 25D ). Similarly, for IL2 measurement anti OKT3 antibody induced elevation in secretion was found to be 121.50 pg/mL while anti-CLEC2D antibodies did not give rise to IL2 secretion more than 4.7 pg/mL ( FIG. 25E ). Taken together, identified therapeutic anti-CLEC2D antibody poses low possibility on immunogenicity reaction as judged by the lack of any T lymphocyte daughter population seen when treated with anti-CLEC2D antibody and also extremely low amount of cytokine secretion as observed with both IFN-γ and IL2. 
     Safety Study Performed with Anti-CLEC2D Monoclonal Antibody in Rat/Non-Human Primate 
     Toxicology studies with therapeutic monoclonal antibodies should be carried out in a species that are pharmacologically relevant, meaning one that both expresses the target antigen recognized by the monoclonal antibody and evokes a similar pharmacological response following antibody binding, similar to that expected in humans. It is required to demonstrate comparable effector function of monoclonal antibodies in animals that can be extended to humans, especially for antibodies with relatively strong effector function, such as, IgG1. Thereby, the most sensitive animal model available for predicting human safety is utilized. However, cross-reactivity, or lack in cross reactivity, can be predicted through a detailed in silico analysis of sequence and structural understanding between the human antigen protein or targeted epitopes and the equivalent proteins in conventional species used for toxicology studies. It is advisable that toxicology assessment should be performed in two relevant species if available, one rodent and one non-rodent, while non-human primates (NHP), such as, cynomolgus monkey, is celebrated as the most suitable species to ethically justify its use and strategies minimizing primate use. 
     In silico understanding of comparative sequence analysis of CLEC2D antigens homologs from Human Rat, Mouse and Cynomolgus moneky, indicated that human CLEC2D antigen shares highest sequence homology (&gt;90%) with cynomolgus monkey CLEC2D homolog while sequence homology against Rat and mouse homologs being less than ˜70%. However, sequences were looked into in detail to identify the presence of the important residues which contacts antibody paratope sequence. The said exercise indicated that all species contain at least 70% of the contact points and interacting amino acid residues conserved and possibly available to interact with anti-CLEC2D antibody. Therefore efforts towards understanding the binding of anti-CLEC2D mono clonal antibodies was attempted through generating surface expressed CLEC2D antigen homologs from Rat, Mouse and cynomolgus monkey species. Flow cytometry based method was employed to assess the binding between antibody and CLEC2D antigen homologs. 
     As can be linked with SEQ IDs 886, 910, 911, 918, full length CLEC2D homologous sequences, from respective species were synthesized and cloned in pCDNA3.1, mammalian expression vector, which were transfected in CHO cells for binding studies through flow cytometry. 
     Transfection with Constructs of CLEC2D Antigen Variants for Homology Study 
     CHO suspension cells at more than 90% viability were used for expression of CLEC2D antigen variants. For 100 ml volume of transfection 1.25×10{circumflex over ( )}8 cells were taken. Cells were centrifuged at 1000-1400 rpm for 4-5 minutes, decanted the spent media and re-suspended in 25 ml of OptiMEM I media. DNA constructs were transfected using Lipofectamine LTX with Plus™ reagent. 50-100 μg of respective pCDNA 3.1, constructs, were used with 1:3 to 1:6 DNA to transfection reagent ratio and 50-100 μl Plus™ reagent was used. DNA and Lipofectamine LTX complex was prepared in 25 ml OptiMEM I and incubated at 20-25° C. for 5 minutes for complex formation. The transfection mix was added slowly to the cell suspension. The cells were incubated for 4-6 hours at 37° C. in a 5% CO2 shaker Incubator at 100-120 RPM. 50 ml of Power CHO2 CD growth media was added to the cells. The cells were incubated at 37° C. in a 5% CO2 shaker Incubator at 100-120 RPM. 2-3 days post transfection 200 ml Power CHO2 CD growth media was added and Glutamax was added from 200 mM stock to achieve final concentration of 2 mM. The cells were incubated at 37° C. in a 5% CO2 shaker Incubator at 100-120 RPM. Cells were analyzed for cell surface antigen binding by flow-cytometry on day 3 to day 6 after transfection. 
     As can be seen in  FIG. 26 , Anti-CLEC2D_antibody clones C5511, C4608, not limited to, developed against human CLEC2D antigen, and exhibited similar binding ranging from 2-4 fold of MFI. This indicates a broad specificity of anti-CLEC2D antibodies towards CLEC2D homologs in both rodent and non-human primate species. 
     
       
         
           
               
             
               
                 TABLE 54 
               
             
            
               
                   
               
               
                 Amino acid sequence recognized by anti-CLEC2D 
               
               
                 antibody 
               
            
           
           
               
               
            
               
                 SEQ ID 
                 Amino acid sequence 
               
               
                 NO 
                 recognized by anti-CLEC2D antibody 
               
               
                   
               
               
                 2561 
                 GLU150-XAA151-THR152-ARG153-GLN154 
               
               
                   
               
               
                 2562 
                 ARG175-XAA176-TYR177-XAA178-GLU179 
               
               
                   
               
               
                 2563 
                 ARG101-XAA102-XAA-103-XAA104-SER105- 
               
               
                   
                 XAA106-ASP107 
               
               
                   
               
               
                 2564 
                 GLU138-XAA139-XAA140-GLN141-XAA142-XAA143- 
               
               
                   
                 LYS144 
               
               
                   
               
               
                 2565 
                 GLU138-GLN139-XAA140-GLN141 
               
               
                   
               
               
                 2566 
                 ARG175-XAA176-TYR177-XAA178-XAA179-ARG180 
               
               
                   
               
               
                 2567 
                 TYR177-XAA179-XAA180-LYS181 
               
               
                   
               
            
           
         
       
     
       
     
       
         
           
               
             
               
                 LENGTHY TABLES 
               
             
            
               
                 The patent application contains a lengthy table section. A copy of the table is available in electronic form from the USPTO web site (http://seqdata.uspto.gov/?pageRequest=docDetail&amp;DocID=US20200291120A1). An electronic copy of the table will also be available from the USPTO upon request and payment of the fee set forth in 37 CFR 1.19(b)(3).