Patent Publication Number: US-2023143831-A1

Title: Antigen-presenting extracellular vesicles, composition containing same, and method for production thereof

Description:
TECHNICAL FIELD 
     The present invention relates to antigen-presenting extracellular vesicles, a composition containing the same, and a method for preparing the same. 
     BACKGROUND ART 
     It is known that antigen-specific T cells (for example, cytotoxic T cells, helper T cells, and the like) play a central role in an immune reaction such as elimination of cancer cells and the like by living bodies or regulation of responses to auto-antigens, allergic substances, and the like. The antigen-specific T cells recognize a binding complex of MHC molecules on cell surfaces of antigen-presenting cells such as dendritic cells or macrophages, and antigens derived from cancer, allergic substances, and the like, at a T cell receptor, and activate, proliferate, and differentiate. The activated antigen-specific T cells specifically injure cancer cells and the like presenting antigens, and regulate responses to auto-antigens, allergic substances, and the like. Therefore, it is considered that activation, proliferation, and differentiation of the antigen-specific T cells are particularly important in the immune reaction. 
     As a method for activating the antigen-specific T cells, not only a method for expressing a chimeric antigen receptor in T cells that has already been put into practical use, but also other methods have been developed. For example, Patent Literature 1 discloses that nanoparticles containing MHC molecules and T-cell costimulatory molecules on surfaces thereof proliferate antigen-specific T cells. In addition, Non Patent Literature 1 discloses that exosomes in which IL-12 is expressed on membranes via PTGFRN proliferate tumor antigen-specific CD8-positive T cells. 
     CITATION LIST 
     Patent Literature 
     
         
         Patent Literature 1: JP 2016-520518 A 
       
    
     Non Patent Literatures
     Non Patent Literature 1: Katherine Kirwin, et al., “Exosome Surface Display of IL-12 Results in Tumor-Retained Pharmacology with Superior Potency and Limited Systemic Exposure Compared to Recombinant IL-12”, Nov. 6, 2019, 34th Annual Meeting of the Society for Immuno-therapy of Cancer   Non Patent Literature 2: Journal of Extracellular Vesicles (2018); 7:1535750   

     SUMMARY OF INVENTION 
     Technical Problem 
     As a novel method capable of activating antigen-specific T cells, the present inventors tried a method using extracellular vesicles containing MHC molecules and T-cell costimulatory molecules in membranes. However, when an attempt was made to active antigen-specific T cells using the extracellular vesicles, it was found for the first time that antigen-specific T cells could not be satisfactorily activated. 
     Therefore, an object of the present invention is to provide extracellular vesicles capable of satisfactorily activating antigen-specific T cells. 
     Solution to Problem 
     In view of the above problems, as a result of conducting intensive studies, the present inventors have surprisingly found that antigen-specific T cells can be satisfactorily activated using extracellular vesicles containing MHC molecules and T-cell stimulatory cytokines in membranes, thereby completing the present invention. 
     Therefore, the present invention includes the followings. 
     [0] An extracellular vesicle presenting an antigen-presenting MHC molecule and a T-cell stimulatory cytokine outside membrane thereof. 
     [1] An antigen-presenting extracellular vesicle, the membrane of which contains: 
     (A) a protein which comprises an antigen-presenting MHC molecule and is capable of presenting the antigen outside the membrane; and 
     (B) a protein which comprises a first T-cell stimulatory cytokine or a subunit thereof and is capable of presenting the first T-cell stimulatory cytokine outside the membrane. 
     [2] The antigen-presenting extracellular vesicle according to [1], wherein the membrane of the antigen-presenting extracellular vesicle contains: 
     (A) a fusion protein or a protein complex which comprises an antigen-presenting MHC molecule, and a membrane protein capable of being expressed in membrane of an extracellular vesicle or a transmembrane domain thereof or a protein capable of binding to membrane of an extracellular vesicle or a domain thereof, and is capable of presenting the antigen outside the membrane; and 
     (B) a fusion protein which comprises a first T-cell stimulatory cytokine or a subunit thereof, and a membrane protein capable of being expressed in membrane of an extracellular vesicle or a transmembrane domain thereof or a protein capable of binding to membrane of an extracellular vesicle or a domain thereof, and is capable of presenting the first T-cell stimulatory cytokine outside the membrane. 
     [3] The antigen-presenting extracellular vesicle according to [1] or [2], wherein the membrane of the antigen-presenting extracellular vesicle contains: 
     (A) a fusion protein or a protein complex which comprises an antigen-presenting MHC molecule and a tetraspanin or a transmembrane domain thereof or MFG-E8 or a domain thereof, and is capable of presenting the antigen outside the membrane; and 
     (B) a fusion protein which comprises a first T-cell stimulatory cytokine or a subunit thereof and a partial sequence of a tetraspanin, and is capable of presenting the first T-cell stimulatory cytokine outside the membrane, in which the partial sequence of the tetraspanin contains at least two transmembrane domains, and the first T-cell stimulatory cytokine is disposed between the two transmembrane domains, or 
     (B) a fusion protein which comprises a first T-cell stimulatory cytokine or a subunit thereof and MFG-E8 or a domain thereof, and is capable of presenting the first T-cell stimulatory cytokine outside the membrane. 
     [4] The antigen-presenting extracellular vesicle according to any one of [1] to [3], wherein the membrane of the antigen-presenting extracellular vesicle contains: 
     (A) a fusion protein capable of presenting an antigen peptide outside the membrane, wherein the fusion protein comprises an amino acid sequence consisting of, from an N-terminal side thereof,
         (A-1) an MHC molecule-restricted antigen peptide,   (A-2) a spacer sequence which may be optionally present,   (A-3) a single chain MHC molecule,   (A-4) a spacer sequence which may be optionally present, and   (A-5) a tetraspanin, or       

     (A) a protein complex capable of presenting an antigen peptide outside the membrane, wherein the protein complex contains: 
     a fusion protein comprising an amino acid sequence consisting of, from an N-terminal side thereof,
         (A-1) an MHC molecule-restricted antigen peptide,   (A-2) a spacer sequence which may be optionally present,   (A-3) an MHC class Iα chain, β 2  microglobulin, an MHC class IIα chain, or an MHC class IIβ chain,   (A-4) a spacer sequence which may be optionally present, and   (A-5) a tetraspanin; and   (A-6) a protein comprising an amino acid sequence of β 2  microglobulin, an MHC class Iα chain, an MHC class IIβ chain, or an MHC class IIα chain; and       

     (B) a fusion protein comprising an amino acid sequence consisting of, from an N-terminal side thereof,
         (B-1) a partial sequence of a tetraspanin containing, from an N-terminal side thereof, a transmembrane domain 1, a small extracellular loop, a transmembrane domain 2, a small intracellular loop, and a transmembrane domain 3,   (B-2) a spacer sequence which may be optionally present,   (B-3) a first T-cell stimulatory cytokine,   (B-4) a spacer sequence which may be optionally present, and   (B-5) a partial sequence of a tetraspanin containing a transmembrane domain 4,       

     the fusion protein being capable of presenting the first T-cell stimulatory cytokine outside the membrane, or 
     (B) a fusion protein comprising an amino acid sequence consisting of, from an N-terminal side thereof,
         (B-3) a first T-cell stimulatory cytokine,   (B-4) a spacer sequence which may be optionally present, and   (B-5) MFG-E8, the fusion protein being capable of presenting the first T-cell stimulatory cytokine outside the membrane.       

     [5] The antigen-presenting extracellular vesicle according to [4], wherein the membrane of the antigen-presenting extracellular vesicle contains: 
     (A) a fusion protein capable of presenting an antigen peptide outside the membrane, in which the fusion protein comprises an amino acid sequence consisting of, from an N-terminal side thereof;
         (A-1) an MHC class I molecule-restricted antigen peptide,   (A-2) a spacer sequence which may be optionally present,   (A-3) a single chain MHC class I molecule,   (A-4) a spacer sequence which may be optionally present, and   (A-5) a tetraspanin.       

     [6] The antigen-presenting extracellular vesicle according to [4], wherein the membrane of the antigen-presenting extracellular vesicle contains: 
     (A) a protein complex capable of presenting an antigen peptide outside the membrane, wherein the protein complex contains: 
     a fusion protein comprising an amino acid sequence consisting of, from an N-terminal side thereof,
         (A-1) an MHC class II molecule-restricted antigen peptide,   (A-2) a spacer sequence which may be optionally present,   (A-3) an MHC class IIβ chain,   (A-4) a spacer sequence which may be optionally present, and   (A-5) a tetraspanin; and   (A-6) a protein comprising an amino acid sequence of an MHC class IIα chain.       

     [7] The antigen-presenting extracellular vesicle according to any one of [1] to [6], wherein the first T-cell stimulatory cytokine is IL-2, IL-4, IL-6, IL-12, a subunit of IL-12, or TGF-β. 
     [8] The antigen-presenting extracellular vesicle according to any one of [1] to [7], wherein the membrane of the antigen-presenting extracellular vesicle contains: 
     (C) a protein which comprises a T-cell costimulatory molecule and is capable of allowing the T-cell costimulatory molecule to interact with T cells. 
     [9] The antigen-presenting extracellular vesicle according to any one of [1] to [8], wherein the membrane of the antigen-presenting extracellular vesicle contains: 
     (C) a fusion protein which comprises a T-cell costimulatory molecule, and a membrane protein capable of being expressed in membrane of an extracellular vesicle or a transmembrane domain thereof or a protein capable of binding to membrane of an extracellular vesicle or a domain thereof, and is capable of allowing the T-cell costimulatory molecule to interact with T cells. 
     The antigen-presenting extracellular vesicle according to any one of [1] to [9], wherein the membrane of the antigen-presenting extracellular vesicle contains: 
     (C) a fusion protein which comprises a T-cell costimulatory molecule, and a tetraspanin or a transmembrane domain thereof or MFG-E8 or a domain thereof, and is capable of allowing the T-cell costimulatory molecule to interact with T cells. 
     [11] The antigen-presenting extracellular vesicle according to any one of [1] to [10], wherein the membrane of the antigen-presenting extracellular vesicle contains: 
     (C) a fusion protein comprising an amino acid sequence consisting of, from an N-terminal side thereof,
         (C-1) a T-cell costimulatory molecule,   (C-2) a spacer sequence which may be present, and   (C-3) a tetraspanin,       

     the fusion protein being capable of allowing the T-cell costimulatory molecule to interact with T cells. 
     [12] The antigen-presenting extracellular vesicle according to any one of [1] to [11], wherein the extracellular vesicle is an exosome. 
     [13] Polynucleotides encoding any one of: 
     (i) the fusion protein or protein complex of (A) defined in any one of [2] to [6]; 
     (ii) the fusion protein of (B) defined in any one of [2] to [4]; and 
     (iii) the fusion protein of (C) defined in any one of [9] to [11]. 
     [14] A vector comprising at least one polynucleotide selected from the polynucleotides according to [13]. 
     [15] A cell transformed with a single vector or a combination of two or more vectors, the vector comprising: 
     (i) a polynucleotide encoding the fusion protein or protein complex of (A) defined in any one of [2] to [6]; 
     (ii) a polynucleotide encoding the fusion protein of (B) defined in any one of [2] to [4]; and optionally, 
     (iii) a polynucleotide encoding the fusion protein of (C) defined in any one of [9] to [11]. 
     [16] A culture supernatant obtained by culturing the cell according to [15]. 
     [17] An antigen-presenting extracellular vesicle obtained from the culture supernatant according to [16]. 
     [18] A method for preparing the antigen-presenting extracellular vesicle according to any one of [1] to [12], the method comprising a step of collecting a culture supernatant obtained by culturing the cell according to [15]. 
     [19] A pharmaceutical composition comprising the antigen-presenting extracellular vesicle according to any one of [1] to [12] and [17] or the culture supernatant according to [16]. 
     [20] A pharmaceutical composition for treating or preventing an infectious disease, comprising the antigen-presenting extracellular vesicle according to any one of [1] to [12] and [17] or the culture supernatant according to [16]. 
     [21] A pharmaceutical composition for treating or preventing cancer, comprising the antigen-presenting extracellular vesicle according to any one of [5] and [7] to [12]. 
     [22] A pharmaceutical composition for treating or preventing an autoimmune disease, comprising the antigen-presenting extracellular vesicle according to any one of [6] to [12]. 
     [23] A pharmaceutical composition for treating or preventing an allergic disease, comprising the antigen-presenting extracellular vesicle according to any one of [6] to [12]. 
     [24] A method for activating and/or proliferating T cells against a specific antigen, comprising contacting the antigen-presenting extracellular vesicle according to any one of [1] to [12] and [17] with T cells in vitro or ex vivo. 
     [25] 
     The antigen-presenting extracellular vesicle according to any one of [1] to [11], wherein the protein or protein complex defined in (A) and the protein or protein complex defined in (B) are fused to each other. 
     [26] 
     The antigen-presenting extracellular vesicle according to any one of [8] to [11], wherein the protein or protein complex defined in (A) and the protein or protein complex defined in (C) are fused to each other. 
     [27] 
     The antigen-presenting extracellular vesicle according to any one of [8] to [11], wherein the protein or the protein complex defined in (B) and the protein or protein complex defined in (C) are fused to each other. 
     [28] 
     The antigen-presenting extracellular vesicle according to any one of [8] to [11], wherein the protein or the protein complex defined in (A), the protein or protein complex defined in (B), and the protein or protein complex defined in (C) are fused to each other. 
     [29] The antigen-presenting extracellular vesicle according to any one of [25] to [27], wherein the extracellular vesicle is an exosome. 
     [30] The pharmaceutical composition according to [21], further containing an immune checkpoint inhibitor. 
     [31] The pharmaceutical composition according to [30], wherein the immune checkpoint inhibitor is present on the membrane of the antigen-presenting extracellular vesicle. 
     [32] The pharmaceutical composition according to [30] or [31], wherein the immune checkpoint inhibitor is selected from the group consisting of an anti-PD-1 antibody or an active fragment thereof, an anti-CTLA-4 antibody or an active fragment thereof, and a PD-L1 antibody or an active fragment thereof. 
     [1A] 
     An antigen-presenting extracellular vesicle, the membrane of which contains, 
     (D) a fusion protein which comprises an antigen-presenting MHC molecule and at least one T-cell stimulatory cytokine or subunit thereof, and is capable of presenting the antigen and the T-cell stimulatory cytokine outside the membrane. 
     [2A] The antigen-presenting extracellular vesicle according to [1A], in wherein the fusion protein comprises the antigen-presenting MHC molecule, the at least one T-cell stimulatory cytokine or subunit thereof, and a membrane protein capable of being localized to membrane of an extracellular vesicle or a transmembrane domain thereof or a protein capable of binding to membrane of an extracellular vesicle or a membrane-binding domain thereof. 
     [3A] The antigen-presenting extracellular vesicle according to [2A], wherein the membrane protein capable of being localized on membrane of an extracellular vesicle or the protein capable of binding to membrane of an extracellular vesicle is a tetraspanin or MFG-E8. 
     [4A] The antigen-presenting extracellular vesicle according to [3A], wherein the fusion protein comprises an amino acid sequence encoding, from an N-terminal side thereof,
         (D-1) an MHC molecule-restricted antigen peptide,   (D-2) a spacer sequence which may be present,   (D-3) a single chain MHC molecule,   (D-4) a spacer sequence which may be present, and   (D-5) a fusion peptide comprising a tetraspanin or a transmembrane domain thereof or MFG-E8 or a transmembrane domain thereof, and the at least one T-cell stimulatory cytokine or subunit thereof, in this order.       

     [5A] The antigen-presenting extracellular vesicle according to [3A], wherein the fusion protein contains an amino acid sequence encoding, from an N-terminal side thereof,
         (D-1) a fusion peptide comprising a tetraspanin or a transmembrane domain thereof or MFG-E8 or a transmembrane domain thereof, and the at least one T-cell stimulatory cytokine or subunit thereof,   (D-2) a spacer sequence which may be optionally present,   (D-3) a single chain MHC molecule,   (D-4) a spacer sequence which may be optionally present, and   (D-5) an MHC molecule-restricted antigen peptide, in this order.       

     [6A] 
     The antigen-presenting extracellular vesicle according to [4A] or [5A], in which the fusion peptide comprises an amino acid sequence encoding, from an N-terminal side thereof, 
     (1) a partial sequence of a tetraspanin containing a transmembrane domain 1, a small extracellular loop, a transmembrane domain 2, a small intracellular loop, and a transmembrane domain 3, 
     (2) a spacer sequence which may be optionally present, 
     (3) the at least one T-cell stimulatory cytokine or subunit thereof, 
     (4) a spacer sequence which may be optionally present, and 
     (5) a partial sequence of a tetraspanin containing a transmembrane domain 4, in this order. 
     [7A] 
     The antigen-presenting extracellular vesicle according to [4A] or [5A], wherein the fusion peptide comprises an amino acid sequence encoding, from an N-terminal side thereof, 
     (1) the at least one T-cell stimulatory cytokine or subunit thereof, 
     (2) a spacer sequence which may be optionally present, and 
     (3) MFG-E8, in this order. 
     [8A] 
     The antigen-presenting extracellular vesicle according to [4A] or [5A], wherein the MHC molecule-restricted antigen peptide is an MHC class I molecule-restricted antigen peptide, and the single chain MHC molecule comprises an extracellular domain of an MHC class Iα chain. 
     [9A] The antigen-presenting extracellular vesicle according to [4A] or [5A], wherein the MHC molecule-restricted antigen peptide is an MHC class II molecule-restricted antigen peptide, and the single chain MHC molecule comprises an extracellular domain of an MHC class IIα chain and/or an extracellular domain of an MHC class IIβ chain. 
     [10A] 
     The antigen-presenting extracellular vesicle according to any one of [1A] to [9A], wherein the membrane of the antigen-presenting extracellular vesicle further contains (C) a protein which comprises at least one T-cell costimulatory molecule and is capable of allowing the T-cell costimulatory molecule to interact with T cells. 
     [11A] 
     The antigen-presenting extracellular vesicle according to [10A], wherein the protein capable of interacting with T cells comprises the at least one T-cell costimulatory molecule, and a membrane protein capable of being expressed in membrane of an extracellular vesicle or a transmembrane domain thereof or a protein capable of binding to membrane of an extracellular vesicle or a domain thereof. 
     [12A] 
     The antigen-presenting extracellular vesicle according to [11A], wherein the protein capable of interacting with T cells comprises the at least one T-cell costimulatory molecule, and a tetraspanin or a transmembrane domain thereof or MFG-E8 or a domain thereof. 
     [13A] 
     The antigen-presenting extracellular vesicle according to [12A], wherein the protein capable of interacting with T cells comprises 
     (C) an amino acid sequence encoding, from an N-terminal side thereof,
         (C-1) the at least one T-cell costimulatory molecule,   (C-2) a spacer sequence which may be optionally present, and   (C-3) a tetraspanin, in this order.       

     [14A] The antigen-presenting extracellular vesicle according to any one of [10A] to [13A], wherein the fusion protein (D) is fused to the protein (C) capable of interacting with T cells. 
     [15A] The antigen-presenting extracellular vesicle according to any one of [1A] to [14A], wherein the extracellular vesicle is an exosome. 
     [1B] A pharmaceutical composition comprising the antigen-presenting extracellular vesicle according to any one of [1A] to [15A] and a pharmacologically acceptable carrier. 
     [1C] A pharmaceutical composition for treating or preventing cancer comprising the antigen-presenting extracellular vesicle according to any one of [1A] to [15A], wherein the antigen peptide preferably includes a cancer antigen peptide. 
     [2C] A pharmaceutical composition for treating or preventing an autoimmune disease comprising the antigen-presenting extracellular vesicle according to any one of [1A] to [15A], wherein the antigen peptide preferably includes an auto-antigen peptide. 
     [3C] A pharmaceutical composition for treating or preventing an allergic disease comprising the antigen-presenting extracellular vesicle according to any one of [1A] to [15A], wherein the antigen peptide preferably includes an allergen. 
     [4C] The pharmaceutical composition according to [1C], further containing an immune checkpoint inhibitor. 
     [5C] The pharmaceutical composition according to [4C], wherein the immune checkpoint inhibitor is present on the membrane of the antigen-presenting extracellular vesicle. 
     [6C] The pharmaceutical composition according to [4C] or [5C], wherein the immune checkpoint inhibitor is selected from the group consisting of an anti-PD-1 antibody or an active fragment thereof, an anti-CTLA-4 antibody or an active fragment thereof, and a PD-L1 antibody or an active fragment thereof. 
     [7C] A pharmaceutical composition for treating or preventing an infectious disease comprising the antigen-presenting extracellular vesicle according to any one of [1A] to [15A] and a pharmacologically acceptable carrier, wherein the antigen peptide is preferably derived from an infectious pathogen that causes an infectious disease. 
     [1D] The antigen-presenting extracellular vesicle according to any one of [1A] to [15A] for use in treating or preventing cancer, wherein the antigen peptide preferably includes a cancer antigen peptide. 
     [2D] The antigen-presenting extracellular vesicle according to any one of [1A] to [15A] for use in treating or preventing an autoimmune disease, wherein the antigen peptide preferably includes an auto-antigen peptide. 
     [3D] The antigen-presenting extracellular vesicle according to any one of [1A] to [15A] for use in treating or preventing an allergic disease, wherein the antigen peptide preferably includes an allergen. 
     [4D] The antigen-presenting extracellular vesicle foe use according to [1D] used together with an immune checkpoint inhibitor. 
     [5D] The antigen-presenting extracellular vesicle for use according to [4D], wherein the immune checkpoint inhibitor is present on the membrane of the antigen-presenting extracellular vesicle. 
     [6D] The antigen-presenting extracellular vesicle for use according to [4D] or [5D], wherein the immune checkpoint inhibitor is selected from the group consisting of an anti-PD-1 antibody or an active fragment thereof, an anti-CTLA-4 antibody or an active fragment thereof, and a PD-L1 antibody or an active fragment thereof. 
     [7D] The antigen-presenting extracellular vesicle according to any one of [1A] to [15A] for use in treating or preventing an infectious disease, wherein the antigen peptide is preferably derived from an infectious pathogen that causes an infectious disease. 
     [1E] Use of the antigen-presenting extracellular vesicle according to any one of [1A] to [15A] in the manufacture of a medicament for treating or preventing cancer, wherein the antigen peptide preferably includes a cancer antigen peptide. 
     [2E] Use of the antigen-presenting extracellular vesicle according to any one of [1A] to [15A] in the manufacture of a medicament for treating or preventing an autoimmune disease, wherein the antigen peptide preferably includes an auto-antigen peptide. 
     [3E] Use of the antigen-presenting extracellular vesicle according to any one of [1A] to [15A] in the manufacture of a medicament for treating or preventing an allergic disease, wherein the antigen peptide preferably includes an allergen. 
     [4E] The use according to [1E], wherein the pharmaceutical is used together with an immune checkpoint inhibitor. 
     [5E] The use according to [4E], wherein the immune checkpoint inhibitor is present on the membrane of the antigen-presenting extracellular vesicle. 
     [6E] The use according to [4E] or [5E], wherein the immune checkpoint inhibitor is selected from the group consisting of an anti-PD-1 antibody or an active fragment thereof, an anti-CTLA-4 antibody or an active fragment thereof, and a PD-L1 antibody or an active fragment thereof. 
     [7E] Use of the antigen-presenting extracellular vesicle according to any one of [1A] to [15A] the manufacture of a medicament for treating or preventing an infectious disease, wherein the antigen peptide is preferably derived from an infectious pathogen that causes an infectious disease. 
     [1F] A method for treating or preventing cancer in a subject, the method comprising: 
     administering an effective amount of the antigen-presenting extracellular vesicle according to any one of [1A] to [15A] to the subject to activate and/or proliferate T cells that recognize a caner antigen in the subject and to allow the activated and/or proliferated T cells to attack cancer cells; wherein the activated and/or proliferated T cells are preferably CD8-positive cytotoxic T cells, and the antigen peptide preferably includes a cancer antigen peptide. 
     [2F] A method for treating or preventing an autoimmune disease in a subject, the method comprising administering an effective amount of the antigen-presenting extracellular vesicle according to any one of [1A] to [15A] to the subject to activate and/or proliferate T cells that recognize an auto-antigen in the subject and to desensitize an immune response to the auto-antigen in the subject, wherein the activated and/or proliferated T cells are preferably CD4-positive regulatory T cells (Treg), and the antigen peptide preferably includes an auto-antigen peptide. 
     [3F] A method for treating or preventing an allergic disease in a subject, wherein a method for treating or preventing an autoimmune disease comprises administering an effective amount of the antigen-presenting extracellular vesicle according to any one of [1A] to [15A] to the subject to activate and/or proliferate T cells that recognize an allergen in the subject and to desensitize an immune response to the auto-antigen in the subject, wherein the activated and/or proliferated T cells are preferably CD4-positive regulatory T cells (Treg), and the antigen peptide preferably includes an auto-antigen peptide. 
     [4F] The method according to [1F], wherein the antigen-presenting extracellular vesicle is administered together with an immune checkpoint inhibitor. 
     [5F] The method according to [4F], wherein the immune checkpoint inhibitor is present on the membrane of the antigen-presenting extracellular vesicle. 
     [6F] The method according to [4F] or [5F], wherein the immune checkpoint inhibitor is selected from the group consisting of an anti-PD-1 antibody or an active fragment thereof, an anti-CTLA-4 antibody or an active fragment thereof, and a PD-L1 antibody or an active fragment thereof. 
     [7F] A method for treating or preventing an infectious disease in a subject, the method comprising: 
     administering an effective amount of the antigen-presenting extracellular vesicle according to any one of [1A] to [15A] to the subject to, 
     1) secrete inflammatory cytokines and to activate innate immunity of the subject, and/or 
     2) provide acquired immunity to an infectious pathogen that causes the infectious disease to the subject, 
     so that, in the subject&#39;s body, the infectious pathogen that causes the infectious disease is eliminated and/or a proliferation of the infectious pathogen is suppressed. 
     [1G] A method for activating and/or proliferating T cells against a specific antigen, the method comprising contacting the antigen-presenting extracellular vesicle according to any one of [1A] to [15A] with T cells in vitro or ex vivo. 
     [1H] A polynucleotide encoding: 
     (i) the fusion protein or protein complex (D) defined in any one of [1A] to [9A]; 
     (ii) the protein (C) capable of interacting with T cells defined in any one of [10A] to [13A]; or 
     (iii) the fusion protein of the fusion protein (D) and the protein (C) capable of interacting with T cells defined in [14A]. 
     [2H] A vector comprising the nucleic acid according to [1H]. 
     Advantageous Effects of Invention 
     According to the present invention, it is possible to satisfactorily activate antigen-specific T cells by using an extracellular vesicle (i.e., antigen-presenting extracellular vesicle) containing an MHC molecule and a T-cell stimulatory cytokine in membrane thereof. 
    
    
     
       BRIEF DESCRIPTION OF DRAWINGS 
         FIG.  1 A  illustrates a model diagram of an antigen peptide-single chain MHC class I molecule (sc-Trimer)-CD81 fusion protein. 
         FIG.  1 B  illustrates an amino acid sequence of the antigen peptide-single chain MHC class I molecule (sc-Trimer)-CD81 fusion protein. 
         FIG.  1 C  illustrates a model diagram of a CD80-CD9 fusion protein. 
         FIG.  1 D  illustrates an amino acid sequence of the CD80-CD9 fusion protein. 
         FIG.  1 E  illustrates a model diagram of a CD63-IL-2 fusion protein. 
         FIG.  1 F  illustrates an amino acid sequence of the CD63-IL-2 fusion protein. 
         FIG.  1 G  illustrates a model diagram of an antigen peptide-MHC class HP chain (sc-Dimer)-CD81 fusion protein. 
         FIG.  1 H  illustrates an amino acid sequence of the antigen peptide-MHC class HO chain (sc-Dimer)-CD81 fusion protein. 
         FIG.  1 I  illustrates an amino acid sequence of an MHC class IIα chain. 
         FIG.  1 J  illustrates a model diagram of a TGF-β-MFG-E8 fusion protein. 
         FIG.  1 K  illustrates an amino acid sequence of the TGF-β-MFG-E8 fusion protein. 
         FIG.  1 L  illustrates a model diagram of a CD81-IL-4 fusion protein. 
         FIG.  1 M  illustrates an amino acid sequence of the CD81-IL-4 fusion protein. 
         FIG.  2 A  illustrates a model diagram of an antigen-presenting extracellular vesicle of Example 1. 
         FIG.  2 B  illustrates a model diagram of an antigen-presenting extracellular vesicle of Example 2. 
         FIG.  2 C  illustrates a model diagram of an antigen-presenting extracellular vesicle of Example 3. 
         FIG.  2 D  illustrates a model diagram of an antigen-presenting extracellular vesicle of Example 4. 
         FIG.  2 E  illustrates a model diagram of an antigen-presenting extracellular vesicle of Example 5. 
         FIG.  2 F  illustrates a model diagram of an antigen-presenting extracellular vesicle of Example 6. 
         FIG.  2 G  illustrates a model diagram of an antigen-presenting extracellular vesicle of Example 7. 
         FIG.  2 H  illustrates a model diagram of an antigen-presenting extracellular vesicle of Example 8. 
         FIG.  2 I  illustrates a model diagram of an antigen-presenting extracellular vesicle of Example 9. 
         FIG.  2 J  illustrates a model diagram of antigen-presenting extracellular vesicles of other embodiments. 
         FIG.  3 A  illustrates results obtained by analyzing fusion proteins contained in the membrane of the antigen-presenting extracellular vesicle of Example 2 by flow cytometry in Test Example 1-1. 
         FIG.  3 B  illustrates results obtained by analyzing fusion proteins contained in the membrane of the antigen-presenting extracellular vesicle of Example 3 by flow cytometry in Test Example 1-2. 
         FIG.  3 C  illustrates results obtained by analyzing fusion proteins contained in the membrane of the antigen-presenting extracellular vesicle of Example 4 by flow cytometry in Test Example 1-3. 
         FIG.  3 D  illustrates results obtained by analyzing fusion proteins contained in the membrane of the antigen-presenting extracellular vesicle of Example 5 by flow cytometry in Test Example 1-4. 
         FIG.  3 E  illustrates results obtained by analyzing fusion proteins contained in the membrane of the antigen-presenting extracellular vesicle of Example 6 by flow cytometry in Test Example 1-5. 
         FIG.  3 F  illustrates results obtained by analyzing fusion proteins contained in the membrane of the antigen-presenting extracellular vesicle of Example 7 by flow cytometry in Test Example 1-6. 
         FIG.  3 G  illustrates results obtained by analyzing fusion proteins contained in the membrane of the antigen-presenting extracellular vesicle of Example 8 by flow cytometry in Test Example 1-7. 
         FIG.  3 H  illustrates results obtained by analyzing fusion proteins contained in the membrane of the antigen-presenting extracellular vesicle of Example 9 by flow cytometry in Test Example 1-8. 
         FIG.  4    illustrates results obtained by evaluating whether the antigen-presenting extracellular vesicles of Examples 1 and 2 activate antigen-specific CD8-positive T cells (OT-1 T cells) in vitro in Test Example 2. 
         FIG.  5    illustrates results obtained by evaluating whether the antigen-presenting extracellular vesicle of Example 2 activates antigen-specific CD8-positive T cells (OT-1) in vivo in Test Example 3. 
         FIG.  6    illustrates results obtained by evaluating whether the antigen-presenting extracellular vesicle of Example 3 activates antigen-specific CD4-positive T cells in vitro in Test Example 4. 
         FIG.  7    illustrates results obtained by evaluating whether the antigen-presenting extracellular vesicle of Example 4 induces differentiation of antigen-specific CD4-positive T cells (OT-2 T cells) into regulatory T cells in vitro in Test Example 5. 
         FIG.  8    illustrates results obtained by evaluating whether the antigen-presenting extracellular vesicles of Examples 3 and 5 induce differentiation of antigen-specific CD4-positive T cells (OT-2 T cells) into Th2T cells in vitro in Test Example 6. 
         FIG.  9    illustrates results obtained by evaluating whether the antigen-presenting extracellular vesicle of Example 6 induces differentiation of antigen-specific CD4-positive T cells into Th1 cells in vitro in Test Example 7. 
         FIG.  10    illustrates results obtained by evaluating whether the antigen-presenting extracellular vesicle of Example 7 induces differentiation of antigen-specific CD4-positive T cells into Th17 cells in vitro in Test Example 8. 
         FIG.  11    illustrates that antigen-specific CD8-positive T cells are remarkably proliferated by the antigen-presenting extracellular vesicles of Examples 1 and 8 in Test Example 9. 
         FIG.  12    illustrates that B16 melanoma cells are remarkably suppressed by the antigen-presenting extracellular vesicle of Example 8 in Test Example 10. 
     
    
    
     DESCRIPTION OF EMBODIMENTS 
     Definitions 
     Extracellular Vesicle 
     The “extracellular vesicle” used in the present specification is not particularly limited as long as it is a vesicle secreted from cells, and examples thereof include exosomes, microvesicles (MV), and apoptotic bodies. 
     The “exosome” used in the present specification means a vesicle of about 20 to about 500 nm (preferably about 20 to about 200 nm, more preferably about 25 to about 150 nm, and still more preferably about 30 to about 100 nm), the vesicle being derived from an endocytosis pathway. Examples of constituent components of the exosome include a protein and a nucleic acid (mRNA, miRNA, or non-coated RNA). The exosome has a function of controlling intercellular communication. Examples of a maker molecule of the exosome include Alix, Tsg101, a tetraspanin, a flotillin, and phosphatidylserine. 
     The “microvesicle” used in the present specification means a vesicle of about 50 to about 1,000 nm, the vesicle being derived from a cytoplasmic membrane. Examples of constituent components of the microvesicle include a protein and a nucleic acid (mRNA, miRNA, non-coated RNA, or the like). The microvesicle has a function of controlling intercellular communication and the like. Examples of a marker molecule of the microvesicle include integrin, selectin, CD40, and CD154. 
     The “apoptotic body” used in the present specification means a vesicle of about 500 to about 2,000 nm, the vesicle being derived from a cytoplasmic membrane. Examples of constituent components of the apoptotic body include a fragmented nucleus and a cell organelle. The apoptotic body has a function of inducing phagocytosis and the like. Examples of a maker molecule of the apoptotic body include Annexin V and phosphatidylserine. 
     The “antigen-presenting extracellular vesicle” used in the present specification means an extracellular vesicle presenting an antigen outside membrane thereof. 
     Major Histocompatibility Gene Complex Molecule 
     The “major histocompatibility complex (hereinafter, also referred to as “MHC”) molecule” used in the present specification is not particularly limited as long as it has an antigen-binding gap and can bind to an antigen to be presented to a T cell, a T cell precursor, or the like. Examples of the MHC molecule include an MHC class I molecule and an MHC class II molecule. The MHC molecule may be derived from any animal species. Examples thereof include a human leukocyte antigen (HLA) in a human and an H2 system in a mouse. 
     HLA corresponding to the MHC class I molecule may be classified into subtypes such as HLA-A, HLA-B, HLA-Cw, HLA-F, and HLA-G. Polymorphism (allele) is known for these subtypes. Examples of polymorphism of HLA-A include HLA-A1, HLA-A0201, and HLA-A24, examples of polymorphism of HLA-B include HLA-B7, HLA-B40, and HLA-B4403, and examples of polymorphism of HLA-Cw include HLA-Cw0301, HLA-Cw0401, and HLA-Cw0602. 
     HLA corresponding to the MHC class II molecule may be classified into subtypes such as HLA-DR, HLA-DQ, and HLA-DP. 
     The MHC molecule described in the present specification is not limited as long as the function thereof can be exhibited, and an amino acid sequence identity of a wild-type amino acid sequence (for example, in a case of an MHC class I molecule: for example, an MHC class Iα chain of SEQ ID NO: 9 or the like, β 2  microglobulin of SEQ ID NO: 7 or the like, a single chain MHC class I molecule of SEQ ID NO: 65 or the like, and the like; and in a case of an MHC class II molecule: for example, an MHC class IIα chain of SEQ ID NO: 71 or the like, an MHC class IIβ chain of SEQ ID NO: 37 or the like, a single chain MHC class II molecule, and the like) may be 80% or more, preferably 90% or more, more preferably 95% or more, still more preferably 98% or more, and further still more preferably 99% or more. Alternatively, the MHC molecule described in the present specification may be obtained by deletion, insertion, and/or substitution of one or a plurality of amino acids with respect to the wild-type amino acid sequence as long as it can exhibit the function thereof. 
     The “antigen-presenting MHC molecule” used in the present specification is not particularly limited as long as it is an MHC molecule presenting an antigen, and examples thereof include an antigen-presenting MHC class I molecule and an antigen-presenting MHC class II molecule. Examples of the “antigen-presenting MHC class I molecule” include a complex of an antigen, an MHC class Iα chain or an extracellular domain thereof, and β 2  microglobulin; a complex of an antigen and a single chain MHC class I molecule; a fusion protein in which an antigen and a single chain MHC class I molecule are bound; and a complex an antigen, and a fusion protein of an extracellular domain of an MHC class Iα chain and another protein or a domain thereof or a fragment thereof (for example, a fusion protein of an extracellular domain of an MHC class Iα chain and an Fc portion of an antibody, a fusion protein of an extracellular domain of an MHC class Iα chain and a transmembrane domain of another membrane protein, and the like) Examples of the “antigen-presenting MHC class II molecule” include a complex of an antigen, an MHC class IIα chain or an extracellular domain thereof, and an MHC class IIβ chain or an extracellular domain thereof; a complex of an antigen and a single chain MHC class II molecule; a complex of a fusion protein in which an antigen and an MHC class IIβ chain are bound and an MHC class IIα chain; and a complex of a fusion protein of an antigen, an extracellular domain of an MHC class IIα chain and another protein or a domain thereof or a fragment thereof (for example, a fusion protein of an extracellular domain of an MHC class IIα chain and an Fc portion of an antibody; a fusion protein of an extracellular domain of an MHC class IIα chain and a transmembrane domain of another membrane protein; and the like), and a fusion protein of an extracellular domain of an MHC class IIβ chain and another protein or a domain thereof or a fragment thereof (for example, a fusion protein of an extracellular domain of an MHC class IIβ chain and an Fc portion of an antibody; a fusion protein of an amino acid sequence containing an extracellular domain of an MHC class IIβ chain and a transmembrane domain of another membrane protein; and the like). 
     The “single chain MHC molecule”, the “single chain MHC class I molecule”, or the “single chain MHC class II molecule” used in the present specification means a fusion protein in which an α chain of an MHC molecule (or an MHC class I molecule or an MHC class II molecule) or an extracellular domain thereof, and a β chain or an extracellular domain thereof or β 2  microglobulin are linked by a spacer sequence, if necessary. Examples of the “single chain MHC class I molecule” include a fusion protein in which an MHC class Iα chain and β 2  microglobulin are linked by a spacer sequence, if necessary. Examples of the “single chain MHC class II molecule” include a fusion protein in which an MHC class IIα chain and an MHC class IIβ chain are linked by a spacer sequence, if necessary. 
     The “protein (or a fusion protein, a protein complex, or the like) which comprises an antigen-presenting MHC molecule and is capable of presenting the antigen (or an antigen peptide) outside membrane” used in the present specification means a protein comprising at least an antigen-presenting MHC molecule and presenting an antigen (or an antigen peptide) outside membrane, in which the protein is capable of presenting an antigen to T cells and the like (a fusion protein, a protein complex, or the like). The “protein (or a fusion protein, a protein complex, or the like) comprising an antigen-presenting MHC molecule and presenting an antigen (or an antigen peptide) outside the membrane” may be expressed in the form of a fusion protein, a protein complex, or the like using a plasmid or the like so that the protein is expressed in membrane of an extracellular vesicle. Alternatively, in a case where a soluble antigen-presenting MHC molecule (although not limited thereto, a fusion protein comprising an MHC class Iα chain and an immunoglobulin heavy chain described in Patent Literature 1; a soluble MHC class I molecule described in JP 2007-161719 A, or the like) is used, the “protein (or a fusion protein, a protein complex, or the like) which comprises an antigen-presenting MHC molecule and is capable of presenting an antigen (or an antigen peptide) outside the membrane” may be a protein in which a soluble antigen-presenting MHC molecule and an extracellular vesicle are bound to membrane of the extracellular vesicle by a lipid linker, a peptide linker, or the like, if necessary (for example, the method described in JP 2018-104341 A or the like may be referred to). Alternatively, the protein may be a mixture of a protein in which a desired tag (for example, a His tag, a FLAG tag, a PNE tag (SEQ ID NO: 79: NYHLENEVARLKKL), or the like) is added to the N-terminus or C-terminus of a soluble antigen-presenting MHC molecule (the tag may be expressed as a fusion protein together with other constituent elements, for example, may be bound to an additionally prepared soluble antigen-presenting MHC molecule by a linker or the like, if necessary), and an extracellular vesicle containing a protein comprising an antibody against the tag or an antigen-binding fragment thereof (for example, scFv, Fab, or a nanobody) (for example, an antibody itself against the tag or an antigen-binding fragment thereof (for example, scFv, Fab, or a nanobody) bound to the membrane of the extracellular vesicle by a linker or the like, if necessary; a fusion protein in which a nanobody for the tag is bound to the N-terminus or C-terminus of a membrane protein capable of being expressed in membrane of an extracellular vesicle or a transmembrane domain thereof) in membrane under desired conditions (for example, the method using a PNE tag and an antibody against the tag described in Raj D, et al., Gut., 2019 June; 68(6): 1052-1064, and the like, may be referred to). 
     Antigen 
     The “antigen” used in the present specification is not particularly limited as long as it can have antigenicity, and includes not only peptide antigens but also non-peptide antigens (for example, constituent elements of a bacterial membrane such as mycolic acid and lipoarabinomannan) such as phospholipids and complex carbohydrates. 
     The “antigen peptide” used in the present specification is not particularly limited as long as it is a peptide that can be an antigen, and may be naturally derived, synthetically derived, or commercially available. Examples of the antigen peptide include, but are not limited to, tumor-associated antigen peptides such as WT-1, an α-fetal protein, MAGE-1, MAGE-3, placental alkaline phosphatase Sialyl-Lewis X, CA-125, CA-19, TAG-72, epithelial glycoprotein 2, 5T4, an α-fetal protein receptor, M2A, tyrosinase, Ras, p53, Her-2/neu, EGF-R, an estrogen receptor, a progesterone receptor, myc, BCR-ABL, HPV-type 16, melanotransferrin, MUC1, CD10, CD19, CD20, CD37, CD45R, an IL-2 receptor a chain, a T cell receptor, prostatic acid phosphatase, GP100, MelanA/Mart-1, gp75/brown, BAGE, S-100, itokeratin, CYFRA21-1, and Ep-CAM; self-antigen peptides such as insulin, glutamic acid decarboxylase, ICA512/IA-2 protein tyrosine phosphatase, ICA12, ICA69, preproinsulin, HSP60, carboxypeptidase H, periferin, GM1-2, vitronectin, β-crystallin, carreticulin, serotransferase, keratin, pyruvate carboxylase, C1, billin 2, nucleosome, ribonucleoprotein, myelin oligodendrocyte glycoprotein, myelin-associated glycoprotein, myelin/oligodendrocyte basic protein, oligodendrocyte-specific protein, myelin basic protein, and proteolipid protein; antigen peptides derived from infectious pathogens such as protozoa (for example, plasmodium, leishmania, and trypanosoma), bacteria (for example, gram-positive cocci, gram-positive rods, gram-negative bacteria, and anaerobic bacteria), fungi (for example,  Aspergillus, Blastomycosis, Candida, Coccidioidomycosis, Cryptococcus, Histoplasma, Paracoccidioidomycosis , and  Sporoslix ), viruses (for example, adenovirus, simple herpesvirus, papillomavirus, respiratory synthiavirus, poxvirus, HIV, influenza virus, and coronavirus such as SARS-CoV or SARS-CoV2), intracellular parasites (for example, Chlamydiaceae, Mycoplasmataceae, Acholeplasma, and Rickettsiaceae), and helminths (for example, nematodes, trematodes, and tapeworms); and other antigen peptides such as prion. 
     The antigen peptide may comprise an allergen that causes allergic symptoms. Examples of the allergen include exogenous peptides such as peptides derived from house dust, mites, animals (for example, companion animals such as cats and dogs), and pollens (for example, Japanese cedar or Japanese cypress), in addition to the peptides derived from protozoa, bacteria, fungi, intracellular parasites, and helminths More specifically, proteins contained in Japanese cedar such as Cryj1 are exemplified. Alternatively, the allergen that causes allergic symptoms may be derived from food. Examples of the allergen that causes allergic symptoms for food include peptides derived from chicken egg, cow milk, wheat, buckwheat, crab, shrimp, and peanut. 
     The “MHC molecule-restricted antigen peptide” used in the present specification means an antigen peptide capable of binding to an MHC molecule in vitro, in vivo, and/or ex vivo. The number of amino acid residues of the “MHC molecule-restricted antigen peptide” is usually about 7 to about 30. Examples of the “MHC molecule-restricted antigen peptide” include an MHC class I molecule-restricted antigen peptide and an MHC class II molecule-restricted antigen peptide. 
     The “MHC class I molecule-restricted antigen peptide” used in the present specification means an antigen peptide capable of binding to an MHC class I molecule in vitro, in vivo, and/or ex vivo. When the MHC class I molecule-restricted antigen peptide is presented outside membrane of the extracellular vesicle, for example, the antigen peptide is recognized by precursor T cells or the like, and cytotoxic T cells or the like can be induced. The number of amino acid residues of the “MHC class I molecule-restricted antigen peptide” is usually about 7 to about 30, preferably about 7 to about 25, more preferably about 7 to about 20, still more preferably about 7 to about 15, and further still more about 7 to about 12. 
     The “MHC class II molecule-restricted antigen peptide” used in the present specification means an antigen peptide capable of binding to an MHC class II molecule in vitro, in vivo, and/or ex vivo. When the MHC class II molecule-restricted antigen peptide is presented outside membrane of the extracellular vesicle, for example, the antigen peptide is recognized by precursor T cells or the like, and α-T cells or the like can be induced. The number of amino acid residues of the “MHC class II molecule-restricted antigen peptide” is usually about 7 to about 30, preferably about 10 to about 25, and more preferably about 12 to about 24. 
     The “MHC molecule-restricted antigen peptide”, the “MHC class I molecule-restricted antigen peptide”, or the “MHC class II molecule-restricted antigen peptide” is not particularly limited as long as it is an antigen peptide capable of binding to an MHC molecule, an MHC class I molecule, or an MHC class II molecule. 
     T-Cell Stimulatory Cytokine 
     The “T-cell stimulatory cytokine” used in the present specification is not particularly limited as long as it is a cytokine capable of stimulating (for example, activating, suppressing, or the like) T cells via a receptor or the like expressed on the membrane of the T cell. Examples of the T-cell stimulatory cytokine include, are not limited to, IL-2, IL-4, IL-6, IL-12, TGF-β, IFN-α, and IFN-γ. Among them, a T-cell stimulatory cytokine capable of forming a multimer of homo or hetero subunits (for example, IL-12, TGF-β, or the like) may be a T-cell stimulatory cytokine comprising a continuous amino acid sequence linked by a peptide linker or the like, if necessary, as long as it is functional (that is, as long as it can have a desired pharmacological activity). 
     The T-cell stimulatory cytokines described in the present specification may be derived from any animal species. Examples of the T-cell stimulatory cytokine include T-cell stimulatory cytokines derived from animals such as mammals, for example, rodents such as a mouse and a rat; lagomorph such as a rabbit; ungulates such as a pig, a cow, a goat, a horse, and a sheep; carnivore such as a dog and a cat; and primates such as a human, a monkey, a rhesus monkey, a crab-eating macaque, a marmoset, an orangutan, and a chimpanzee. The T-cell stimulatory cytokine described in the present specification is preferably derived from rodents or primates, and more preferably derived from a mouse or a human. 
     The T-cell stimulatory cytokine described in the present specification may have an amino acid sequence identity of 80% or more, preferably 90% or more, more preferably 95% or more, still more preferably 98% or more, and further still more preferably 99% or more with respect to a wild-type amino acid sequence thereof (for example, in the case of IL-2, for example, SEQ ID NO: 25 or the like; and in the case of IL-4, for example, SEQ ID NO: 53 or the like), as long as it can exhibit the function thereof. Alternatively, the T-cell stimulatory cytokine described in the present specification may be obtained by deletion, insertion, and/or substitution of one or a plurality of amino acids with respect to the wild-type amino acid sequence as long as it can exhibit the function thereof. 
     The “protein which comprises a (first or second) T-cell stimulatory cytokine and is capable of presenting the (first or second) T-cell stimulatory cytokine outside membrane” used in the present specification means a protein which comprises at least a T-cell stimulatory cytokine and is capable of presenting the T-cell stimulatory cytokine outside membrane of an extracellular vesicle. The “protein which comprises a (first or second) T-cell stimulatory cytokine and is capable of presenting the (first or second) T-cell stimulatory cytokine outside membrane” may be expressed by using a plasmid or the like as a fusion protein having a fragment comprising a T-cell stimulatory cytokine and a membrane protein or a transmembrane domain thereof so that the protein is expressed in the membrane of the extracellular vesicle. Alternatively, in a case where a soluble T-cell stimulatory cytokine (examples thereof include, but are not limited to, a T-cell stimulatory cytokine itself; a fusion protein of a T-cell stimulatory cytokine and an Fc portion of an antibody; and a complex of a T-cell stimulatory cytokine and an antibody that recognizes the T-cell stimulatory cytokine or an antigen-binding fragment thereof (for example, scFv, Fab, or a nanobody)) is used, the “protein which comprises a (first or second) T-cell stimulatory cytokine and is capable of presenting the (first or second) T-cell stimulatory cytokine outside membrane” may be a protein in which a soluble T-cell stimulatory cytokine and an extracellular vesicle are bound to membrane of an extracellular vesicle by a lipid linker, a peptide linker, or the like, if necessary (for example, the method described in JP 2018-104341 A or the like may be referred to). Alternatively, the protein may be a mixture of a protein in which a desired tag (for example, a His tag, a FLAG tag, or a PNE tag) is added to the N-terminus or C-terminus of a soluble T-cell stimulatory cytokine (the tag may be expressed as a fusion protein together with other constituent elements, for example, may be bound to an additionally prepared soluble T-cell stimulatory cytokine by a linker or the like, if necessary), and an extracellular vesicle containing a protein comprising an antibody against the tag or an antigen-binding fragment thereof (for example, scFv, Fab, or a nanobody) (for example, an antibody itself against the tag or an antigen-binding fragment thereof (for example, scFv, Fab, or a nanobody) bound to the membrane of the extracellular vesicle by a linker or the like, if necessary; a fusion protein in which a nanobody for the tag is bound to the N-terminus or C-terminus of a membrane protein capable of being expressed in membrane of an extracellular vesicle or a transmembrane domain thereof) in membrane under desired conditions (for example, the method using a PNE tag and an antibody against the tag described in Raj D, et al., Gut., 2019 June; 68(6): 1052-1064, and the like, may be referred to). Note that in a case of a T-cell stimulatory cytokine formed by multimers of subunits, when one of the subunits is a protein that can be presented outside membrane of an extracellular vesicle, the remaining subunits do not need to be in a form that can be presented outside the membrane. When one of the subunits is a protein capable of being presented outside membrane of an extracellular vesicle, a functional T-cell stimulatory cytokine can be constructed outside the membrane of the extracellular vesicle by adding or co-expressing other subunits. 
     T-Cell Costimulatory Molecule 
     The “T-cell costimulatory molecule” used in the present specification means a molecule that can contribute to activation of T cells by interacting with a molecule present on membrane of a T cell such as CD28 or CD134. Examples of the T-cell costimulatory molecule include, but are not limited to, molecules such as CD80 and CD86, or extracellular domains thereof or functional fragments thereof; antibodies such as an anti-CD28 antibody and an anti-CD134 antibody or antigen-binding fragments thereof (for example, scFv, Fab, or a nanobody); and a fusion protein (or a complex or an aggregate) of them with a transmembrane domain of another protein or an Fc portion of an antibody. 
     The T-cell costimulatory molecule described in the present specification may be derived from any animal species. Examples of the T-cell costimulatory molecule include T-cell costimulatory molecules derived from animals such as mammals, for example, rodents such as a mouse, a rat, a hamster, and a guinea pig; lagomorph such as a rabbit; ungulates such as a pig, a cow, a goat, a horse, and a sheep; carnivora such as a dog and a cat; and primates such as a human, a monkey, a rhesus monkey, a crab-eating macaque, a marmoset, an orangutan, and a chimpanzee. The T-cell costimulatory molecule described in the present specification is preferably derived from rodents or primates, and more preferably derived from a mouse or a human. 
     The T-cell costimulatory molecule described in the present specification may have an amino acid sequence identity of 80% or more, preferably 90% or more, more preferably 95% or more, still more preferably 98% or more, and further still more preferably 99% or more with respect to a wild-type amino acid sequence thereof (for example, in the case of CD80, for example, SEQ ID NO: 67 or the like), as long as it can exhibit the function described above. Alternatively, the T-cell costimulatory molecule described in the present specification may be obtained by deletion, insertion, and/or substitution of one or a plurality of amino acids with respect to the wild-type amino acid sequence as long as it can exhibit the function thereof. 
     The “protein which comprises a T-cell costimulatory molecule and is capable of allowing the T-cell costimulatory molecule to interact with T cells” used in the present specification means a protein which comprises at least a T-cell costimulatory molecule and is capable of interacting with a molecule present in membrane of the T cell. That is, it means that the at least a portion capable of interacting with T cells present in the T-cell costimulatory molecule is located outside the membrane of the extracellular vesicle. The “protein which comprises a T-cell costimulatory molecule and is capable of allowing the T-cell costimulatory molecule to interact with T cells” may be expressed by using a plasmid or the like so that it is expressed in the membrane of the extracellular vesicle. Alternatively, in a case where a soluble T-cell costimulatory molecule (examples thereof include, but are not limited to, a fusion protein of an extracellular domain of CD80 and an Fc portion of an antibody; and an anti-CD28 antibody or an antigen-binding fragment thereof (for example, scFv, Fab, or a nanobody)) is used, the “protein which comprises a T-cell costimulatory molecule and is capable of allowing the T-cell costimulatory molecule to interact with T cells” may be a protein in which a soluble T-cell costimulatory molecule and an extracellular vesicle are bound to membrane of the extracellular vesicle by a lipid linker, a spacer sequence, or the like, if necessary (for example, the method described in JP 2018-104341 A or the like may be referred to). Alternatively, the protein may be a mixture of a protein in which a desired tag (for example, a His tag, a FLAG tag, or a PNE tag) is added to the N-terminus or C-terminus of a soluble T-cell costimulatory molecule (the tag may be expressed as a fusion protein together with other constituent elements, for example, may be bound to an additionally prepared soluble T-cell costimulatory molecule by a linker or the like, if necessary), and an extracellular vesicle containing a protein comprising an antibody against the tag or an antigen-binding fragment thereof (for example, scFv, Fab, or a nanobody) (for example, an antibody itself against the tag or an antigen-binding fragment thereof (for example, scFv, Fab, or a nanobody) bound to the membrane of the extracellular vesicle by a linker or the like, if necessary; a fusion protein in which a nanobody for the tag is bound to the N-terminus or C-terminus of a membrane protein capable of being expressed in membrane of an extracellular vesicle or a transmembrane domain thereof) in membrane under desired conditions (for example, the method using a PNE tag and an antibody against the tag described in Raj D, et al., Gut., 2019 June; 68(6): 1052-1064, and the like, may be referred to). 
     As the “membrane protein capable of being expressed in membrane of an extracellular vesicle or the transmembrane domain thereof” used in the present specification, any membrane protein or a transmembrane domain thereof can be selected as long as it can be expressed in the membrane of the extracellular vesicle. The “membrane protein capable of being expressed in membrane of an extracellular vesicle or a transmembrane domain thereof” is preferably a membrane protein known to be capable of being expressed in an extracellular vesicle (for example, exosome or the like) (for example, a tetraspanin, CD58, ICAM-1, PTGFRN (for example, see Non Patent Literature 1, WO 2019/183578 A, and the like), and the like), or a transmembrane domain thereof. 
     As the “protein capable of binding to membrane of an extracellular vesicle or the domain thereof” used in the present specification, any protein or a domain thereof can be selected as long as it can be bound in the membrane of the extracellular vesicle. The “protein capable of binding to membrane of an extracellular vesicle or the domain thereof” is preferably a protein known to be capable of binding to membrane of an extracellular vesicle (for example, exosome or the like) (for example, MFG-E8 or a domain thereof (for example, a C1 or C2 domain of MFG-E8 described in Alain Delcayre, et al., Blood Cells, Molecules, and Diseases 35 (2005) 158-168)). 
     The “membrane protein capable of being expressed in membrane of an extracellular vesicle or the transmembrane domain thereof” or the “protein capable of binding to membrane of an extracellular vesicle or the domain thereof” described in the present specification may be derived from any animal species. Examples of the T-cell stimulatory cytokine include T-cell stimulatory cytokines derived from animals such as mammals, for example, rodents such as a mouse and a rat; lagomorph such as a rabbit, ungulates such as a pig, a cow, a goat, a horse, and a sheep; carnivora such as a dog and a cat; and primates such as a human, a monkey, a rhesus monkey, a crab-eating macaque, a marmoset, an orangutan, and a chimpanzee. The “membrane protein capable of being expressed in membrane of an extracellular vesicle or the transmembrane domain thereof” or the “protein capable of binding to membrane of an extracellular vesicle or the domain thereof” described in the present specification is preferably derived from rodents or primates, and is more preferably derived from a mouse or a human. 
     According to Non Patent Literature 2, markers of mammalian extracellular vesicles are classified as follows. 
     Examples of a membrane protein or a GPI anchor protein that can be used as a marker protein of an extracellular vesicle include: 
     1) Tissue Non-Specific 
     tetraspanins (CD63, CD9, CD81, and CD82), other multiple transmembrane type membrane proteins (CD47 and hetero trimer G proteins (guanine nucleotide-binding proteins (GNA)), 
     MHC class I (HLA-A/B/C, H2-K/D/Q), 
     integrin (ITGA/ITGB), a transferrin receptor (TFR2); 
     LAMP1/2; 
     heparan sulfate proteoglycans ((including syndecan (SDC)); 
     extracellular matrix metalloprotease inducer (EMMPRIN) (also referred to as BSG or CD147); 
     ADAM10; 
     CD73 that is a GPI anchored 5′ nucleotidase (NT5E), 
     CD55 and CD59 that are GPI anchored complement binding proteins; and 
     sonic hedgehog protein (SHH); and 
     2) Cell/Tissue Specific 
     several tetraspanins: TSPAN8 (epithelial specific), CD37, and CD53 (leukocyte-specific); 
     PECAM1 (endothelial specific); 
     ERBB2 (breast cancer specific); 
     EPCAM (epithelial specific); 
     CD90 (THY1) (mesenchymal stem cell-specific); 
     CD45 (PTPRC) (immune cell-specific), CD41 (ITGA2B), or CD42a (GP9) (platelet-specific); 
     glycophorin A (GYPA) (erythroid specific); 
     CD14 (monocyte specific), MHC class II (HLA-DR/DP/DQ, H2-A); 
     CD3 (T cell specific); 
     acetylcholinesterase/AChE-S (neuronal cell-specific), AChE-E (erythroid specific); and 
     amyloid βA4/APP (neuronal cell-specific). 
     Therefore, although not limited thereto, a protein that is a marker of an extracellular vesicle may be used as the “membrane protein capable of being expressing in membrane of an extracellular vesicle” or the “the protein capable of binding to membrane of an extracellular vesicle” in the present invention. 
     The “tetraspanin” used in the present specification means a protein belonging to a tetraspanin family (for example, but are not limited to, CD9, CD53, CD63, CD81, CD82, CD151, and the like). The tetraspanin usually contains, from an N-terminal side thereof, a transmembrane domain 1 (hereinafter, referred to as “TM1”), a small extracellular loop (hereinafter, referred to as “SEL”), a transmembrane domain 2 (hereinafter, referred to as “TM2”), a small intracellular loop (hereinafter, referred to as “SIL”), a transmembrane domain 3 (hereinafter, referred to as “TM3”), a large extracellular loop (hereinafter, referred to as “LEL”), and a transmembrane domain 4 (hereinafter, referred to as “TM4”), and thus is a quadruple transmembrane type, and both the N-terminus and the C-terminus are present on the cytoplasmic side. For example, in a case where the tetraspanin is mouse CD63 (amino acid sequences: 1 to 238, SEQ ID NO: 27), the tetraspanin may typically contain TM1, SEL, TM2, SIL, and TM3 in the amino acid sequence from about 1 to about 110, LEL in the amino acid sequence from about 111 to about 200, and TM4 in the amino acid sequence from about 201 to about 238. 
     Each domain (for example, TM1, SEL, SIL, LTL, or the like) in the “tetraspanin” described in the present specification may be derived from the same tetraspanin, or may be derived from different tetraspanins in whole or in part. 
     The tetraspanin described in the present specification may have an amino acid sequence identity of 80% or more, preferably 90% or more, more preferably 95% or more, still more preferably 98% or more, and further still more preferably 99% or more with respect to a wild-type amino acid sequence thereof (for example, in the case of CD9 with a full length, for example, SEQ ID NO: 21 or the like; in the case of CD63 with a full length, for example, SEQ ID NO: 27 or the like; and in the case of CD81 with a full length, for example, SEQ ID NO: 15 or the like), as long as it can be expressed in the membrane of the extracellular vesicle. Alternatively, the tetraspanin described in the present specification may be obtained by deletion, insertion, and/or substitution of one or a plurality of amino acids with respect to the wild-type amino acid sequence as long as it can be expressed in the membrane of the extracellular vesicle. 
     A partial sequence of the tetraspanin (for example, each domain; a partial sequence containing TM1, SEL, TM2, SIL, and TM3 (for example, in the case of CD63, SEQ ID NO: 57 or the like; and in the case of CD81, SEQ ID NO: 61 or the like); a partial sequence containing TM4 (for example, in the case of CD63, SEQ ID NO: 59 or the like; and in the case of CD81, SEQ ID NO: 63 or the like)) described in the present specification may have an amino acid sequence identity of 80% or more, preferably 90% or more, more preferably 95% or more, still more preferably 98% or more, and further still more preferably 99% or more with respect to a wild-type amino acid sequence thereof. Alternatively, the partial sequence of the tetraspanin described in the present specification may be obtained by deletion, insertion, and/or substitution of one or a plurality of amino acids with respect to the wild-type amino acid sequence. 
     MFG-E8 described in the present specification may have an amino acid sequence identity of 80% or more, preferably 90% or more, more preferably 95% or more, still more preferably 98% or more, and further still more preferably 99% or more with respect to a wild-type amino acid sequence thereof (for example, SEQ ID NO: 49 or the like), as long as it can bind to the membrane of the extracellular vesicle. Alternatively, MFG-E8 described in the present specification may be obtained by deletion, insertion, and/or substitution of one or a plurality of amino acids with respect to the wild-type amino acid sequence as long as it can bind to the membrane of the extracellular vesicle. 
     CD58, PTGFRN, or the like described in the present specification may have an amino acid sequence identity of 80% or more, preferably 90% or more, more preferably 95% or more, still more preferably 98% or more, and further still more preferably 99% or more with respect to a wild-type amino acid sequence thereof, as long as it can be expressed in the membrane of the extracellular vesicle or can bind to the membrane of the extracellular vesicle. Alternatively, CD58, PTGFRN, or the like described in the present specification may be obtained by deletion, insertion, and/or substitution of one or a plurality of amino acids with respect to the wild-type amino acid sequence as long as it can be expressed in the membrane of the extracellular vesicle or can bind to the membrane of the extracellular vesicle. 
     Spacer Sequence 
     The “spacer sequence” used in the present specification means any sequence having at least one amino acid residue that is present between two or more proteins or partial sequences or domains thereof. The spacer sequence can be used, for example, when two or more proteins or partial sequences or domains thereof are linked. The spacer sequence contains a peptide linker. A length of the amino acid residue of the spacer sequence is usually 1 to about 50, preferably about 2 to about 28, and more preferably about 4 to about 25. Examples of the spacer sequence include, but are not limited to, (GGGXS) n G m  (wherein, X is independently A or G each time it appears, n is 1 to 8, and n, and m is 0 to 3) (for example, SEQ ID NO: 5, 11, 29, 39, or the like); (GGGS) n G m  (wherein, n is 1 to 10, and m is 0 to 3); and T a S b (GGX) n G m , (wherein, X is independently S or T each time it appears, n is 1 to 8, m is 0 to 3, a is 0 or 1, and b is 0 or 1) (for example, SEQ ID NO: 77 or the like). 
     Antigen-Presenting Extracellular Vesicles Described in Present Specification 
     In an embodiment of the present invention, there is provided an extracellular vesicle presenting an antigen-presenting MHC molecule and a T-cell stimulatory cytokine outside membrane (the model is illustrated in (1) of  FIG.  2 J ). 
     Such an extracellular vesicle may present an antigen-presenting MHC molecule and a T-cell stimulatory cytokine outside membrane thereof by containing proteins specified in the following (A) and (B), or may present an antigen-presenting MHC molecule and a T-cell stimulatory cytokine outside membrane thereof by containing a protein specified in (D). 
     Alternatively, an antigen-presenting MHC molecule and a T-cell stimulatory cytokine may be attached to membrane surface of an isolated extracellular vesicle later. An attachment method is not particularly limited, an antigen-presenting MHC molecule and a T-cell stimulatory cytokine may be attached to membrane surface by binding each phospholipid to an antigen-presenting MHC molecule and a T-cell stimulatory cytokine and incorporating a new lipid moiety into membrane of an extracellular vesicle. Phosphatidylserine is present on the surface of the extracellular vesicle. Therefore, each protein obtained by fusing an antigen-presenting MHC molecule or a T-cell stimulatory cytokine desired to be presented to MFG-E8 binding to phosphatidylserine is synthesized and purified, and the fusion protein and an extracellular vesicle are mixed, such that an extracellular vesicle presenting an antigen-presenting MHC molecule and a T-cell stimulatory cytokine on membrane surface can be prepared. In addition, an antigen-presenting MHC molecule to which a PNEtag is attached and a T-cell stimulatory cytokine may be added later to an extracellular vesicle pre-expressing a peptide neoepitope (PNE) nanobody to be presented on membrane surface of the extracellular vesicle. A biotinylated antigen-presenting MHC molecule and a T-cell stimulatory cytokine may be added to the extracellular vesicle expressing streptavidin to be presented on the membrane surface of the extracellular vesicle. 
     In an embodiment of the present invention, the extracellular vesicle may present a plurality of kinds (2, 3, 4, and 5 kinds) of antigen-presenting MHC molecules and a plurality of kinds (2, 3, 4, and 5 kinds) of T-cell stimulatory cytokines (in order to identify each T-cell stimulatory cytokine, hereinafter, it may be referred to as a first T-cell stimulatory cytokine, a second T-cell stimulatory cytokine, third or higher T-cell stimulatory cytokines, and the like) outside the membrane. Alternatively, the extracellular vesicle may be an extracellular vesicle presenting one kind of an antigen-presenting MHC molecule and a plurality of kinds of cell stimulatory cytokines outside membrane (a model of an extracellular vesicle presenting one kind of an antigen-presenting MHC molecule and two kinds of T-cell stimulatory cytokines outside membrane is illustrated in (3) of  FIG.  2 J ). 
     In an embodiment of the present invention, there is provided an antigen-presenting extracellular vesicle the membrane of which contains: 
     (A) a protein which contains an antigen-presenting MHC molecule and is capable of presenting the antigen outside membrane; and 
     (B) a protein which contains a first T-cell stimulatory cytokine and is capable of presenting the first T-cell stimulatory cytokine outside membrane. 
     Constitutional Requirement (A) 
     The “protein which comprises an antigen-presenting MHC molecule and is capable of presenting the antigen outside membrane” of the (A) above may comprise another protein or a domain thereof, or the like in addition to the antigen-presenting MHC molecule as long as it is a protein capable of presenting an antigen outside membrane of an extracellular vesicle. 
     In an embodiment of the present invention, the (A) above is a fusion protein or a protein complex which comprises an antigen-presenting MHC molecule, and a membrane protein capable of being expressed in membrane of an extracellular vesicle or a transmembrane domain thereof or a protein capable of binding to membrane of an extracellular vesicle or a domain thereof, and is capable of presenting the antigen outside membrane. 
     In an embodiment of the present invention, the (A) above is a fusion protein or a protein complex which comprises an antigen-presenting MHC molecule, and a tetraspanin or a transmembrane domain thereof or MFG-E8 or a domain thereof, and is capable of presenting the antigen outside membrane. 
     In an embodiment of the present invention, the (A) above is 
     (A) a fusion protein capable of presenting an antigen peptide outside membrane, in which the fusion protein comprises an amino acid sequence consisting of, from an N-terminal side thereof,
         (A-1) an MHC molecule-restricted antigen peptide,   (A-2) a spacer sequence which may be present,   (A-3) a single chain MHC molecule,   (A-4) a spacer sequence which may be present, and   (A-5) a tetraspanin, or       

     (A) a protein complex capable of presenting an antigen peptide outside membrane, in which the protein complex contains, 
     a fusion protein comprising an amino acid sequence consisting of, from an N-terminal side thereof,
         (A-1) an MHC molecule-restricted antigen peptide,   (A-2) a spacer sequence which may be present,   (A-3) an MHC class Iα chain, β 2  microglobulin, an MHC class IIα chain, or an MHC class IIβ chain,   (A-4) a spacer sequence which may be present, and   (A-5) a tetraspanin;       

     and
         (A-6) a protein comprising an amino acid sequence off 32 microglobulin, an MHC class Iα chain, an MHC class IIβ chain, or an MHC class IIα chain.       

     In an embodiment of the present invention, the (A) above is 
     (A) a fusion protein capable of presenting an antigen peptide outside membrane, in which the fusion protein comprises an amino acid sequence consisting of, from an N-terminal side thereof,
         (A-1) an MHC class I molecule-restricted antigen peptide,   (A-2) a spacer sequence which may be present,   (A-3) a single chain MHC class I molecule,   (A-4) a spacer sequence which may be present, and   (A-5) a tetraspanin.       

     In addition, in an embodiment of the present invention, the (A) above is 
     (A) a fusion protein capable of presenting an antigen peptide outside membrane, in which the fusion protein contains an amino acid sequence consisting of, from an N-terminal side thereof,
         (A-1) an MHC class II molecule-restricted antigen peptide,   (A-2) a spacer sequence which may be present,   (A-3) a single chain MHC class II molecule,   (A-4) a spacer sequence which may be present, and   (A-5) a tetraspanin.       

     In an embodiment of the present invention, the (A) above is 
     (A) a protein complex capable of presenting an antigen peptide outside membrane, in which the protein complex contains: 
     a fusion protein comprising an amino acid sequence consisting of, from an N-terminal side thereof,
         (A-1) an MHC class I molecule-restricted antigen peptide,   (A-2) a spacer sequence which may be present,   (A-3) β 2  microglobulin,   (A-4) a spacer sequence which may be present, and   (A-5) a tetraspanin;       

     and
         (A-6) a protein comprising an amino acid sequence of an MHC class Iα chain.       

     In addition, in an embodiment of the present invention, the (A) above is 
     (A) a protein complex capable of presenting an antigen peptide outside membrane, in which the protein complex contains: 
     a fusion protein comprising an amino acid sequence consisting of, from an N-terminal side thereof,
         (A-1) an MHC class I molecule-restricted antigen peptide,   (A-2) a spacer sequence which may be present,   (A-3) an MHC class Iα chain,   (A-4) a spacer sequence which may be present, and   (A-5) a tetraspanin;       

     and
         (A-6) a protein comprising an amino acid sequence of β 2  microglobulin.       

     In addition, in an embodiment of the present invention, the (A) above is (A) a protein complex capable of presenting an antigen peptide outside membrane, in which the protein complex contains: 
     a fusion protein comprising an amino acid sequence consisting of, from an N-terminal side thereof,
         (A-1) an MHC class II molecule-restricted antigen peptide,   (A-2) a spacer sequence which may be present,   (A-3) an MHC class IIβ chain,   (A-4) a spacer sequence which may be present, and   (A-5) a tetraspanin; and   (A-6) a protein comprising an amino acid sequence of an MHC class IIα chain.       

     In addition, in an embodiment of the present invention, the (A) above is 
     (A) a protein complex capable of presenting an antigen peptide outside membrane, in which the protein complex contains: 
     a fusion protein comprising an amino acid sequence consisting of, from an N-terminal side thereof,
         (A-1) an MHC class II molecule-restricted antigen peptide,   (A-2) a spacer sequence which may be present,   (A-3) an MHC class IIα chain,   (A-4) a spacer sequence which may be present, and   (A-5) a tetraspanin;   and   (A-6) a protein comprising an amino acid sequence of an MHC class IIβ chain.       

     In an embodiment of the present invention, in a case where the (A-3) above is a “single chain MHC class I molecule”, the “single chain MHC class I molecule” consists of, from an N-terminal side thereof, β 2  microglobulin (for example, SEQ ID NO: 7 or the like, or a sequence having an amino acid sequence identity thereto of 80% or more, preferably 90% or more, more preferably 95% or more, still more preferably 98% or more, and further still more preferably 99% or more), a spacer sequence which may be present (when present, for example, SEQ ID NOS: 5, 11, 29, 39, 77, and the like), and an MHC class Iα chain (for example, SEQ ID NO: 9 or the like, or a sequence having an amino acid sequence identity thereto of 80% or more, preferably 90% or more, more preferably 95% or more, still more preferably 98% or more, and further still more preferably 99% or more). In an embodiment of the present invention, in a case where the (A-3) above is a “single chain MHC class I molecule”, the “single chain MHC class I molecule” contains SEQ ID NO: 65 or a sequence having an amino acid sequence identity thereto of 80% or more, preferably 90% or more, more preferably 95% or more, still more preferably 98% or more, and further still more preferably 99% or more. 
     In an embodiment of the present invention, in a case where the (A-3) above is a “single chain MHC class II molecule”, the “single chain MHC class II molecule” consists of, from an N-terminal side thereof, an MHC class IIβ chain, a spacer sequence which may be present, and an MHC class IIα chain. 
     In an embodiment of the present invention, in a case where the (A-3) and/or (A-6) above is “β 2  microglobulin”, the “β 2  microglobulin” comprises SEQ ID NO: 7 or a sequence having an amino acid sequence identity thereto of 80% or more, preferably 90% or more, more preferably 95% or more, still more preferably 98% or more, and further still more preferably 99% or more. 
     In an embodiment of the present invention, in a case where the (A-3) and/or (A-6) above is an “MHC class Iα chain”, the “MHC class Iα chain” comprises SEQ ID NO: 9 or a sequence having an amino acid sequence identity thereto of 80% or more, preferably 90% or more, more preferably 95% or more, still more preferably 98% or more, and further still more preferably 99% or more. 
     In an embodiment of the present invention, in a case where the (A-3) and/or (A-6) above is an “MHC class IIβ chain”, the “MHC class IIβ chain” comprises SEQ ID NO: 37 or a sequence having an amino acid sequence identity thereto of 80% or more, preferably 90% or more, more preferably 95% or more, still more preferably 98% or more, and further still more preferably 99% or more. 
     In an embodiment of the present invention, in a case where the (A-3) and/or (A-6) above is an “MHC class IIα chain”, the “MHC class IIα chain” comprises SEQ ID NO: 71 or a sequence having an amino acid sequence identity thereto of 80% or more, preferably 90% or more, more preferably 95% or more, still more preferably 98% or more, and further still more preferably 99% or more. 
     The “spacer sequence which may be present” of (A-2) and (A-4) in each of the embodiments may be independently selected when present. When (A-2) is present, for example, the spacer sequence may be, for example, a spacer sequence of SEQ ID NO: 5, 11, 29, 39, 77, or the like. When (A-4) is present, for example, the spacer sequence may be, for example, a spacer sequence of SEQ ID NO: 5, 11, 29, 39, 77, or the like. 
     In an embodiment of the present invention, the tetraspanin of (A-5) in each of the embodiments is selected from the group consisting of CD9, CD63, and CD81. In an embodiment of the present invention, the tetraspanin of (A-5) in each of the embodiments is CD81 (preferably, SEQ ID NO: 15 or the like or a sequence having an amino acid sequence identity thereto of 80% or more, preferably 90% or more, more preferably 95% or more, still more preferably 98% or more, and further still more preferably 99% or more). 
     In an embodiment of the present invention, the (A) above is 
     (A) a fusion protein capable of presenting an antigen peptide outside membrane, in which an amino acid sequence consists of, from an N-terminal side thereof,
         (A-1) an MHC class I molecule-restricted antigen peptide,   (A-2) a spacer sequence of SEQ ID NO: 5,   (A-3) a single chain MHC class I molecule of SEQ ID NO: 65 (or a sequence having an amino acid sequence identity thereto of 80% or more, preferably 90% or more, more preferably 95% or more, still more preferably 98% or more, and further still more preferably 99% or more), and   (A-5) a tetraspanin of SEQ ID NO: 15 (or a sequence having an amino acid sequence identity thereto of 80% or more, preferably 90% or more, more preferably 95% or more, still more preferably 98% or more, and further still more preferably 99% or more).       

     In an embodiment of the present invention, the (A) above is 
     (A) a protein complex capable of presenting an antigen peptide outside membrane, in which the protein complex contains: 
     a fusion protein of which an amino acid sequence consists of, from an N-terminal side thereof,
         (A-1) an MHC class II molecule-restricted antigen peptide,   (A-2) a spacer sequence of SEQ ID NO: 39,   (A-3) an MHC class IIβ chain of SEQ ID NO: 37 (or a sequence having an amino acid sequence identity thereto of 80% or more, preferably 90% or more, more preferably 95% or more, still more preferably 98% or more, and further still more preferably 99% or more), and   (A-5) a tetraspanin of SEQ ID NO: 15 (or a sequence having an amino acid sequence identity thereto of 80% or more, preferably 90% or more, more preferably 95% or more, still more preferably 98% or more, and further still more preferably 99% or more);       

     and 
     (A-6) an MHC class IIα chain of SEQ ID NO: 71 (or a sequence having an amino acid sequence identity thereto of 80% or more, preferably 90% or more, more preferably 95% or more, still more preferably 98% or more, and further still more preferably 99% or more). 
     Constitutional Requirement (B) 
     The “protein which comprises a first T-cell stimulatory cytokine and is capable of presenting the first T-cell stimulatory cytokine outside membrane” of the (B) above may comprise another protein or a domain thereof, or the like in addition to the first T-cell stimulatory cytokine as long as it is a protein capable of presenting the first T-cell stimulatory cytokine outside membrane. 
     In an embodiment of the present invention, the (B) above is a fusion protein which comprises a first T-cell stimulatory cytokine, and a membrane protein capable of being expressed in membrane of an extracellular vesicle or a transmembrane domain thereof or a protein capable of binding to membrane of an extracellular vesicle or a domain thereof, and is capable of presenting the first T-cell stimulatory cytokine outside membrane. 
     In an embodiment of the present invention, the (B) above is 
     (B) a fusion protein which comprises a first T-cell stimulatory cytokine and a partial sequence of a tetraspanin and is capable of presenting the first T-cell stimulatory cytokine outside membrane, in which the partial sequence of the tetraspanin contains at least two transmembrane domains and the first T-cell stimulatory cytokine is disposed between the two transmembrane domains, or 
     (B) a fusion protein which comprises a first T-cell stimulatory cytokine and MFG-E8 or a domain thereof and is capable of presenting the first T-cell stimulatory cytokine. 
     Examples of the expression “the partial sequence of the tetraspanin contains at least two transmembrane domains and the first T-cell stimulatory cytokine is disposed between the two transmembrane domains” used in the present specification include a case where the partial sequence of the tetraspanin contains at least TM1 and TM2 of the tetraspanin, and the first T-cell stimulatory cytokine is disposed between TM1 and TM2, and a case where the partial sequence of the tetraspanin contains at least TM3 and TM4 of the tetraspanin, and the first T-cell stimulatory cytokine is disposed between TM3 and TM4. 
     In an embodiment of the present invention, the (B) above is 
     (B) a fusion protein comprising an amino acid sequence consisting of, from an N-terminal side thereof,
         (B-1) a partial sequence of a tetraspanin containing, from an N-terminal side thereof, a transmembrane domain 1, a small extracellular loop, a transmembrane domain 2, a small intracellular loop, and a transmembrane domain 3,   (B-2) a spacer sequence which may be present,   (B-3) a first T-cell stimulatory cytokine,   (B-4) a spacer sequence which may be present, and   (B-5) a partial sequence of a tetraspanin containing a transmembrane domain 4,       

     the fusion protein being capable of presenting the first T-cell stimulatory cytokine outside membrane, or 
     (B) a fusion protein comprising an amino acid sequence consisting of, from an N-terminal side thereof;
         (B-3) a first T-cell stimulatory cytokine,   (B-4) a spacer sequence which may be present, and   (B-5) MFG-E8,       

     the fusion protein being capable of presenting the first T-cell stimulatory cytokine outside membrane. 
     As disclosed in WO 2016/139354 A, it has been reported that the tetraspanin can be expressed in membranes even when a large extracellular loop (LEL) thereof is entirely or partially replaced by a different amino acid sequence. Therefore, the first T-cell stimulatory cytokine of (B-3) may be inserted in place of the LEL of the tetraspanin or may be inserted at any site in the LEL of the tetraspanin or a partial sequence thereof, by a spacer sequence which may be present. 
     The “partial sequence of the tetraspanin containing a transmembrane domain 1, a small extracellular loop, a transmembrane domain 2, a small intracellular loop, and a transmembrane domain 3” of (B-1) usually does not contain a transmembrane domain 4 of the tetraspanin. The “partial sequence of the tetraspanin containing a transmembrane domain 1, a small extracellular loop, a transmembrane domain 2, a small intracellular loop, and a transmembrane domain 3” of (B-1) may contain a large extracellular loop or a partial sequence thereof. In (B-1), the transmembrane domain 1, the small extracellular loop, the transmembrane domain 2, the small intracellular loop, and the transmembrane domain 3 may be sequences derived from different tetraspanins, respectively, or all the domains may be sequences derived from the same tetraspanin. Preferably, in (B-1), all the transmembrane domain 1, the small extracellular loop, the transmembrane domain 2, the small intracellular loop, and the transmembrane domain 3 may be sequences derived from the same tetraspanin. 
     In an embodiment of the present invention, in (B-1), all the partial sequences of the tetraspanin containing a transmembrane domain 1, a small extracellular loop, a transmembrane domain 2, a small intracellular loop, and a transmembrane domain 3 are partial sequences derived from CD9, CD63, or CD81. In an embodiment of the present invention, all the partial sequences of the tetraspanin containing a transmembrane domain 1, a small extracellular loop, a transmembrane domain 2, a small intracellular loop, and a transmembrane domain 3 of (B-1) are preferably partial sequences derived from CD63 or CD81 (preferably, SEQ ID NO: 57, SEQ ID NO: 61, or the like, or a sequence having an amino acid sequence identity thereto of 80% or more, preferably 90% or more, more preferably 95% or more, still more preferably 98% or more, and further still more preferably 99% or more). 
     The “partial sequence of the tetraspanin containing a transmembrane domain 4” of (B-5) usually does not contain a transmembrane domain 1, a small extracellular loop, a transmembrane domain 2, a small intracellular loop, and a transmembrane domain 3 of the tetraspanin. The “partial sequence of the tetraspanin containing a transmembrane domain 4” of (B-5) may contain a large extracellular loop or a partial sequence thereof. The transmembrane domain 4 in (B-5) may be a sequence derived from a tetraspanin different from that in (B-1), or may be a sequence derived from the same tetraspanin as that in (B-1). Preferably, the transmembrane domain 4 in (B-5) is a sequence derived from the same tetraspanin as that in (B-1). In an embodiment of the present invention, in (B-5), the partial sequence of the tetraspanin containing a transmembrane domain 4 is a partial sequence derived from CD9, CD63, or CD81. In an embodiment of the present invention, the partial sequence of the tetraspanin containing a transmembrane domain 4 of (B-5) is a partial sequence derived from CD63 or CD81 (preferably, SEQ ID NO: 59, SEQ ID NO: 63, or the like, or a sequence having an amino acid sequence identity thereto of 80% or more, preferably 90% or more, more preferably 95% or more, still more preferably 98% or more, and further still more preferably 99% or more). 
     In an embodiment of the present invention, the “partial sequence of the tetraspanin containing a transmembrane domain 1, a small extracellular loop, a transmembrane domain 2, a small intracellular loop, and a transmembrane domain 3” of (B-1) is a partial sequence derived from CD63 (preferably, SEQ ID NO: 57 or the like or a sequence having an amino acid sequence identity thereto of 80% or more, preferably 90% or more, more preferably 95% or more, still more preferably 98% or more, and further still more preferably 99% or more), and the “partial sequence of the tetraspanin containing a transmembrane domain 4” of (B-5) is a partial sequence derived from CD63 (preferably, SEQ ID NO: 59 or the like or a sequence having an amino acid sequence identity thereto of 80% or more, preferably 90% or more, more preferably 95% or more, still more preferably 98% or more, and further still more preferably 99% or more). In an embodiment of the present invention, the “partial sequence of the tetraspanin containing a transmembrane domain 1, a small extracellular loop, a transmembrane domain 2, a small intracellular loop, and a transmembrane domain 3” of (B-1) is a partial sequence derived from CD81 (preferably, SEQ ID NO: 61 or the like or a sequence having an amino acid sequence identity thereto of 80% or more, preferably 90% or more, more preferably 95% or more, still more preferably 98% or more, and further still more preferably 99% or more), and the “partial sequence of the tetraspanin containing a transmembrane domain 4” of (B-5) is a partial sequence derived from CD81 (preferably, SEQ ID NO: 63 or the like or a sequence having an amino acid sequence identity thereto of 80% or more, preferably 90% or more, more preferably 95% or more, still more preferably 98% or more, and further still more preferably 99% or more). 
     The fusion protein of the (B) above is a fusion protein comprising a partial sequence of a tetraspanin, and in a case where one or more of the (A) above and (C) present in some cases described below contain a fusion protein comprising an amino acid sequence of a tetraspanin, the fusion protein of the (B) above may be a fusion protein different from the fusion protein of the (A) above and/or (C) present in some cases described below, or may constitute a part of the fusion protein of the (A) above and/or (C) present in some cases described below. The expression that the fusion protein of the (B) above “constitutes a part of the fusion protein of the (A) above and/or (C) present in some cases described below” includes, for example, a case where the tetraspanin of (A-5) constitutes the fusion protein of (B), and/or a case where a tetraspanin of (C-3) present in some cases described below is the fusion protein of (B). 
     The “MFG-E8” of the (B-5) above is preferably SEQ ID NO: 49 or the like or a sequence having an amino acid sequence identity thereto of 80% or more, preferably 90% or more, more preferably 95% or more, still more preferably 98% or more, and further still more preferably 99% or more. 
     In an embodiment of the present invention, in (B-3) of each of the embodiments, the first T-cell stimulatory cytokine is IL-2, IL-4, IL-6, IL-12, or TGF-β. In an embodiment of the present invention, the first T-cell stimulatory cytokine in (B-3) in each of the embodiments is IL-2 (preferably, SEQ ID NO: 25 or the like or a sequence having an amino acid sequence identity thereto of 80% or more, preferably 90% or more, more preferably 95% or more, still more preferably 98% or more, and further still more preferably 99% or more), IL-4 (preferably, SEQ ID NO: 53 or the like or a sequence having an amino acid sequence identity thereto of 80% or more, preferably 90% or more, more preferably 95% or more, still more preferably 98% or more, and further still more preferably 99% or more), or TGF-β (preferably, SEQ ID NO: 73 or the like or a sequence having an amino acid sequence identity thereto of 80% or more, preferably 90% or more, more preferably 95% or more, still more preferably 98% or more, and further still more preferably 99% or more). 
     The “spacer sequence which may be present” in (B-2) and (B-4) in each of the embodiments may be independently selected when present. When (B-2) is present, for example, the spacer sequence may be, for example, a spacer sequence of SEQ ID NO: 5, 11, 29, 39, 77, or the like. When (B-4) is present, for example, the spacer sequence may be, for example, a spacer sequence of SEQ ID NO: 5, 11, 29, 39, 77, or the like. 
     In an embodiment of the present invention, the (B) above is 
     (B) a fusion protein of which an amino acid sequence consists of, from an N-terminal side thereof,
         (B-1) a partial sequence of a tetraspanin of SEQ ID NO: 57 (or a sequence having an amino acid sequence identity thereto of 80% or more, preferably 90% or more, more preferably 95% or more, still more preferably 98% or more, and further still more preferably 99% or more),   (B-2) a spacer sequence of SEQ ID NO: 29,   (B-3) a first T-cell stimulatory cytokine that is IL-2 of SEQ ID NO: 25 (or a sequence having an amino acid sequence identity thereto of 80% or more, preferably 90% or more, more preferably 95% or more, still more preferably 98% or more, and further still more preferably 99% or more),   (B-4) a spacer sequence of SEQ ID NO: 29, and   (B-5) a partial sequence of a tetraspanin of SEQ ID NO: 59 (or a sequence having an amino acid sequence identity thereto of 80% or more, preferably 90% or more, more preferably 95% or more, still more preferably 98% or more, and further still more preferably 99% or more),       

     the fusion protein being capable of presenting the first T-cell stimulatory cytokine outside membrane. 
     In an embodiment of the present invention, the (B) above is a fusion protein capable of presenting the first T-cell stimulatory cytokine of SEQ ID NO: 31 (or a sequence having an amino acid sequence identity thereto of 80% or more, preferably 90% or more, more preferably 95% or more, still more preferably 98% or more, and further still more preferably 99% or more), outside membrane. 
     In an embodiment of the present invention, the (B) above is 
     (B) a fusion protein of which an amino acid sequence consists of, from an N-terminal side thereof,
         (B-1) a partial sequence of a tetraspanin of SEQ ID NO: 61 (or a sequence having an amino acid sequence identity thereto of 80% or more, preferably 90% or more, more preferably 95% or more, still more preferably 98% or more, and further still more preferably 99% or more),   (B-2) a spacer sequence of SEQ ID NO: 29,   (B-3) a first T-cell stimulatory cytokine that is IL-4 of SEQ ID NO: 53 (or a sequence having an amino acid sequence identity thereto of 80% or more, preferably 90% or more, more preferably 95% or more, still more preferably 98% or more, and further still more preferably 99% or more),   (B-4) a spacer sequence of SEQ ID NO: 29, and   (B-5) a partial sequence of a tetraspanin of SEQ ID NO: 63 (or a sequence having an amino acid sequence identity thereto of 80% or more, preferably 90% or more, more preferably 95% or more, still more preferably 98% or more, and further still more preferably 99% or more),       

     the fusion protein being capable of presenting the first T-cell stimulatory cytokine outside membrane. 
     In an embodiment of the present invention, the (B) above is a fusion protein capable of presenting the first T-cell stimulatory cytokine of SEQ ID NO: 55 (or a sequence having an amino acid sequence identity thereto of 80% or more, preferably 90% or more, more preferably 95% or more, still more preferably 98% or more, and further still more preferably 99% or more), outside membrane. 
     In an embodiment of the present invention, the above (B) is 
     (B) a fusion protein of which an amino acid sequence consists of, from an N-terminal side thereof,
         (B-3) a first T-cell stimulatory cytokine that is TGF-β of SEQ ID NO: 73 (or a sequence having an amino acid sequence identity thereto of 80% or more, preferably 90% or more, more preferably 95% or more, still more preferably 98% or more, and further still more preferably 99% or more),   (B-4) a spacer sequence of SEQ ID NO: 29, and   (B-5) MFG-E8 of SEQ ID NO: 49 (or a sequence having an amino acid sequence identity thereto of 80% or more, preferably 90% or more, more preferably 95% or more, still more preferably 98% or more, and further still more preferably 99% or more),       

     the fusion protein being capable of presenting the first T-cell stimulatory cytokine outside membrane. 
     In an embodiment of the present invention, the (B) above is a fusion protein capable of presenting the first T-cell stimulatory cytokine of SEQ ID NO: 75 (or a sequence having an amino acid sequence identity thereto of 80% or more, preferably 90% or more, more preferably 95% or more, still more preferably 98% or more, and further still more preferably 99% or more), outside membrane. 
     Second (or Higher) T-Cell Stimulatory Cytokines 
     The antigen-presenting extracellular vesicle described in the present specification may further contain second (or higher) T-cell stimulatory cytokines in addition to the first T-cell stimulatory cytokine. Therefore, in an embodiment of the present invention, the antigen-presenting extracellular vesicle described in the present specification may further contain a second T-cell stimulatory cytokine. In particular, in a case where the MHC molecule capable of presenting an antigen is an MHC class II molecule capable of presenting an antigen, it is preferable that the antigen-presenting extracellular vesicle described in the present specification contains a second T-cell stimulatory cytokine. 
     The second (or higher) T-cell stimulatory cytokines may be inserted into, for example, the (B) above (for example, the second (or higher) T-cell stimulatory cytokines may be linked to the N-terminus and/or the C-terminus of the “first T-cell stimulatory cytokine” of (B-3) by a spacer sequence or the like, if necessary). Alternatively, similar to the first T-cell stimulatory cytokine, the second (or higher) T-cell stimulatory cytokines may be contained in the membrane of the antigen-presenting extracellular vesicle described in the present specification as a protein (or a fusion protein) different from the protein (or the fusion protein) of the constitutional requirement (B) described in the present specification by having the same configuration as that of the constitutional requirement (B) described in the present specification. 
     In an embodiment of the present invention, the second T-cell stimulatory cytokine is IL-2, IL-4, IL-6, IL-12, or TGF-β. In an embodiment of the present invention, the second T-cell stimulatory cytokine is TGF-β (preferably, SEQ ID NO: 73 or the like or a sequence having an amino acid sequence identity thereto of 80% or more, preferably 90% or more, more preferably 95% or more, still more preferably 98% or more, and further still more preferably 99% or more). 
     In an embodiment of the present invention, the first T-cell stimulatory cytokine is IL-2 or IL-4 (preferably, SEQ ID NO: 25, SEQ ID NO: 53, or the like or a sequence having an amino acid sequence identity thereto of 80% or more, preferably 90% or more, more preferably 95% or more, still more preferably 98% or more, and further still more preferably 99% or more), and the second T-cell stimulatory cytokine is TGF-β (preferably, SEQ ID NO: 73 or a sequence having an amino acid sequence identity thereto of 80% or more, preferably 90% or more, more preferably 95% or more, still more preferably 98% or more, and further still more preferably 99% or more). 
     In an embodiment of the present invention, the antigen-presenting extracellular vesicle described in the present specification is an antigen-presenting extracellular vesicle the membrane of which contains: 
     (A) a fusion protein or a protein complex which contains an antigen-presenting MHC molecule, and a membrane protein capable of being expressed in membrane of an extracellular vesicle or a transmembrane domain thereof or a protein capable of binding to membrane of an extracellular vesicle or a domain thereof, and is capable of presenting the antigen outside membrane; and 
     (B) a fusion protein which contains a first T-cell stimulatory cytokine, and a membrane protein capable of being expressed in membrane of an extracellular vesicle or a transmembrane domain thereof or a protein capable of binding to membrane of an extracellular vesicle or a domain thereof, and is capable of presenting the first T-cell stimulatory cytokine outside membrane. 
     In an embodiment of the present invention, the antigen-presenting extracellular vesicle described in the present specification is an antigen-presenting extracellular vesicle the membrane of which contains: 
     (A) a fusion protein or a protein complex which contains an antigen-presenting MHC molecule and a tetraspanin or a transmembrane domain thereof or MFG-E8 or a domain thereof, and is capable of presenting the antigen outside membrane; and 
     (B) a fusion protein which contains a first T-cell stimulatory cytokine and a partial sequence of a tetraspanin, and is capable of presenting the first T-cell stimulatory cytokine outside membrane, in which the partial sequence of the tetraspanin contains at least two transmembrane domains, and the first T-cell stimulatory cytokine is disposed between the two transmembrane domains, or 
     (B) a fusion protein which contains a first T-cell stimulatory cytokine and MFG-E8 or a domain thereof, and is capable of presenting the first T-cell stimulatory cytokine outside membrane. 
     In an embodiment of the present invention, the antigen-presenting extracellular vesicle described in the present specification is an antigen-presenting extracellular vesicle the membrane of which contains: 
     (A) a fusion protein capable of presenting an antigen peptide outside membrane, in which the fusion protein contains an amino acid sequence consisting of, from an N-terminal side thereof,
         (A-1) an MHC molecule-restricted antigen peptide,   (A-2) a spacer sequence which may be present,   (A-3) a single chain MHC molecule,   (A-4) a spacer sequence which may be present, and   (A-5) a tetraspanin, or       

     (A) a protein complex capable of presenting an antigen peptide outside membrane, in which the protein complex contains, 
     a fusion protein comprising an amino acid sequence consisting of, from an N-terminal side thereof,
         (A-1) an MHC molecule-restricted antigen peptide,   (A-2) a spacer sequence which may be present,   (A-3) an MHC class Iα chain, β 2  microglobulin, an MHC class IIα chain, or an MHC class IIβ chain,   (A-4) a spacer sequence which may be present, and   (A-5) a tetraspanin, and   (A-6) a protein comprising an amino acid sequence of β 2  microglobulin, an MHC class Iα chain, an MHC class IIβ chain, or an MHC class IIα chain; and       

     (B) a fusion protein comprising an amino acid sequence consisting of, from an N-terminal side thereof,
         (B-1) a partial sequence of a tetraspanin containing, from an N-terminal side thereof, a transmembrane domain 1, a small extracellular loop, a transmembrane domain 2, a small intracellular loop, and a transmembrane domain 3,   (B-2) a spacer sequence which may be present,   (B-3) a first T-cell stimulatory cytokine,   (B-4) a spacer sequence which may be present, and   (B-5) a partial sequence of a tetraspanin containing a transmembrane domain 4,       

     the fusion protein being capable of presenting the first T-cell stimulatory cytokine outside membrane, or 
     (B) a fusion protein comprising an amino acid sequence consisting of, from an N-terminal side thereof,
         (B-3) a first T-cell stimulatory cytokine,   (B-4) a spacer sequence which may be present, and   (B-5) MFG-E8,       

     the fusion protein being capable of presenting the first T-cell stimulatory cytokine outside membrane. 
     In an embodiment of the present invention, the antigen-presenting extracellular vesicle described in the present specification is an antigen-presenting extracellular vesicle the membrane of which contains: 
     (A) a fusion protein capable of presenting an antigen peptide outside membrane, in which the fusion protein contains an amino acid sequence consisting of, from an N-terminal side thereof,
         (A-1) an MHC class I molecule-restricted antigen peptide,   (A-2) a spacer sequence which may be present,   (A-3) a single chain MHC class I molecule,   (A-4) a spacer sequence which may be present, and   (A-5) a tetraspanin.       

     In an embodiment of the present invention, the antigen-presenting extracellular vesicle described in the present specification is an antigen-presenting extracellular vesicle the membrane of which contains: 
     (A) a protein complex capable of presenting an antigen peptide outside membrane, in which the protein complex contains: 
     a fusion protein comprising an amino acid sequence consisting of, from an N-terminal side thereof,
         (A-1) an MHC class II molecule-restricted antigen peptide,   (A-2) a spacer sequence which may be present,   (A-3) an MHC class IIβ chain,   (A-4) a spacer sequence which may be present, and   (A-5) a tetraspanin;       

     and
         (A-6) a protein comprising an amino acid sequence of an MHC class IIα chain.       

     In an embodiment of the present invention, the first T-cell stimulatory cytokine is IL-2, IL-4, IL-6, IL-12, or TGF-β, and provides the antigen-presenting extracellular vesicle described in the present specification. 
     In an embodiment of the present invention, the antigen-presenting extracellular vesicle is the extracellular vesicle described in the present specification that further presents a T-cell costimulatory molecule outside membrane (exemplifying a model thereof in (2) of  FIG.  2 J ). 
     Such an extracellular vesicle may present a T-cell costimulatory molecule outside membrane by containing a protein specified in the following (C) in membrane thereof. 
     Alternatively, a T-cell costimulatory molecule may be attached to membrane surface of an isolated extracellular vesicle later. An attachment method is not particularly limited, an antigen-presenting MHC molecule and a T-cell stimulatory cytokine may be attached to membrane surface by binding each phospholipid to a T-cell costimulatory molecule and incorporating a new lipid moiety into membrane of an extracellular vesicle. 
     In an embodiment of the present invention, the antigen-presenting extracellular vesicle described in the present specification is an antigen-presenting extracellular vesicle the membrane of which contains: 
     (C) a protein which comprises a T-cell costimulatory molecule and is capable of allowing the T-cell costimulatory molecule to interact with T cells. 
     Constitutional Requirement (C) 
     The “protein which comprises a T-cell costimulatory molecule and is capable of allowing the T-cell costimulatory molecule to interact with T cells” of the (C) above may contain another protein or a domain thereof, or the like in addition to the T-cell costimulatory molecule as long as it is a protein capable of allowing a T-cell costimulatory molecule to interact with T cells. 
     In an embodiment of the present invention, the (C) above is a fusion protein which comprises a T-cell costimulatory molecule, and a membrane protein capable of being expressed in membrane of an extracellular vesicle or a transmembrane domain thereof or a protein capable of binding to membrane of an extracellular vesicle or a domain thereof, and is capable of allowing the T-cell costimulatory molecule to interact with T cells. 
     In an embodiment of the present invention, the (C) above is a fusion protein which comprises a T-cell costimulatory molecule, and a tetraspanin or a transmembrane domain thereof or MFG-E8 or a domain thereof, and is capable of allowing the T-cell costimulatory molecule to interact with T cells. 
     In an embodiment of the present invention, the above (C) is 
     (C) a fusion protein comprising an amino acid sequence consisting of, from an N-terminal side thereof,
         (C-1) a T-cell costimulatory molecule,   (C-2) a spacer sequence which may be present, and   (C-3) a tetraspanin,       

     the fusion protein being capable of allowing the T-cell costimulatory molecule to interact with T cells. 
     In an embodiment of the present invention, the T-cell costimulatory molecule of (C-1) is CD80 or CD86. In an embodiment of the present invention, the T-cell costimulatory molecule in (C-1) is CD80 (preferably, SEQ ID NO: 67 or the like or a sequence having an amino acid sequence identity thereto of 80% or more, preferably 90% or more, more preferably 95% or more, still more preferably 98% or more, and further still more preferably 99% or more). 
     The “spacer sequence which may be present” of (C-2) may be, for example, a spacer sequence of SEQ ID NO: 5, 11, 29, 39, 77, or the like when present. 
     In an embodiment of the present invention, the tetraspanin of (C-3) is selected from the group consisting of CD9, CD63, and CD81. In an embodiment of the present invention, the tetraspanin in (C-3) is CD9 (preferably, SEQ ID NO: 21 or the like or a sequence having an amino acid sequence identity thereto of 80% or more, preferably 90% or more, more preferably 95% or more, still more preferably 98% or more, and further still more preferably 99% or more). 
     In an embodiment of the present invention, the above (C) is 
     (C) a fusion protein of which an amino acid sequence consists of, from an N-terminal side thereof,
         (C-1) a T-cell costimulatory molecule that is CD80 of SEQ ID NO: 67 (or a sequence having an amino acid sequence identity thereto of 80% or more, preferably 90% or more, more preferably 95% or more, still more preferably 98% or more, and further still more preferably 99% or more), and   (C-3) a tetraspanin of SEQ ID NO: 21 (or a sequence having an amino acid sequence identity thereto of 80% or more, preferably 90% or more, more preferably 95% or more, still more preferably 98% or more, and further still more preferably 99% or more),       

     the fusion protein being capable of allowing the T-cell costimulatory molecule to interact with T cells. 
     In an embodiment of the present invention, the (C) above is a fusion protein capable of allowing the T-cell costimulatory molecule of SEQ ID NO: 69 (or a sequence having an amino acid sequence identity thereto of 80% or more, preferably 90% or more, more preferably 95% or more, still more preferably 98% or more, and further still more preferably 99% or more), to interact with T cells. 
     In an embodiment of the present invention, the antigen-presenting extracellular vesicle described in the present specification is an antigen-presenting extracellular vesicle the membrane of which contains: 
     (A) a fusion protein of which an amino acid sequence consists of, from an N-terminal side thereof,
         (A-1) an MHC class I molecule-restricted antigen peptide,   (A-2) a spacer sequence of SEQ ID NO: 5,   (A-3) a single chain MHC class I molecule of SEQ ID NO: 65 (or a sequence having an amino acid sequence identity thereto of 80% or more, preferably 90% or more, more preferably 95% or more, still more preferably 98% or more, and further still more preferably 99% or more), and   (A-5) a tetraspanin of SEQ ID NO: 15 (or a sequence having an amino acid sequence identity thereto of 80% or more, preferably 90% or more, more preferably 95% or more, still more preferably 98% or more, and further still more preferably 99% or more),       

     the fusion protein being capable of presenting an antigen peptide outside membrane; and 
     (B) a fusion protein of which an amino acid sequence consists of, from an N-terminal side thereof,
         (B-1) a partial sequence of a tetraspanin of SEQ ID NO: 57 (or a sequence having an amino acid sequence identity thereto of 80% or more, preferably 90% or more, more preferably 95% or more, still more preferably 98% or more, and further still more preferably 99% or more),   (B-2) a spacer sequence of SEQ ID NO: 29,   (B-3) a first T-cell stimulatory cytokine that is IL-2 of SEQ ID NO: 25 (or a sequence having an amino acid sequence identity thereto of 80% or more, preferably 90% or more, more preferably 95% or more, still more preferably 98% or more, and further still more preferably 99% or more),   (B-4) a spacer sequence of SEQ ID NO: 29, and   (B-5) a partial sequence of a tetraspanin of SEQ ID NO: 59 (or a sequence having an amino acid sequence identity thereto of 80% or more, preferably 90% or more, more preferably 95% or more, still more preferably 98% or more, and further still more preferably 99% or more),       

     the fusion protein being capable of presenting the first T-cell stimulatory cytokine outside membrane. 
     In an embodiment of the present invention, the antigen-presenting extracellular vesicle described in the present specification is an antigen-presenting extracellular vesicle the membrane of which contains: 
     (A) a fusion protein of which an amino acid sequence consists of, from an N-terminal side thereof,
         (A-1) an MHC class I molecule-restricted antigen peptide,   (A-2) a spacer sequence of SEQ ID NO: 5,   (A-3) a single chain MHC class I molecule of SEQ ID NO: 65 (or a sequence having an amino acid sequence identity thereto of 80% or more, preferably 90% or more, more preferably 95% or more, still more preferably 98% or more, and further still more preferably 99% or more), and   (A-5) a tetraspanin of SEQ ID NO: 15 (or a sequence having an amino acid sequence identity thereto of 80% or more, preferably 90% or more, more preferably 95% or more, still more preferably 98% or more, and further still more preferably 99% or more),       

     the fusion protein being capable of presenting an antigen peptide outside membrane; and 
     (B) a fusion protein capable of presenting the first T-cell stimulatory cytokine of SEQ ID NO: 31 (or a sequence having an amino acid sequence identity thereto of 80% or more, preferably 90% or more, more preferably 95% or more, still more preferably 98% or more, and further still more preferably 99% or more), outside membrane. 
     In an embodiment of the present invention, the antigen-presenting extracellular vesicle described in the present specification is an antigen-presenting extracellular vesicle the membrane of which contains: 
     (A) a fusion protein of which an amino acid sequence consists of, from an N-terminal side thereof,
         (A-1) an MHC class I molecule-restricted antigen peptide,   (A-2) a spacer sequence of SEQ ID NO: 5,   (A-3) a single chain MHC class I molecule of SEQ ID NO: 65 (or a sequence having an amino acid sequence identity thereto of 80% or more, preferably 90% or more, more preferably 95% or more, still more preferably 98% or more, and further still more preferably 99% or more), and   (A-5) a tetraspanin of SEQ ID NO: 15 (or a sequence having an amino acid sequence identity thereto of 80% or more, preferably 90% or more, more preferably 95% or more, still more preferably 98% or more, and further still more preferably 99% or more), the fusion protein capable of presenting an antigen peptide outside membrane;       

     (B) a fusion protein of which an amino acid sequence consists of, from an N-terminal side thereof,
         (B-1) a partial sequence of a tetraspanin of SEQ ID NO: 57 (or a sequence having an amino acid sequence identity thereto of 80% or more, preferably 90% or more, more preferably 95% or more, still more preferably 98% or more, and further still more preferably 99% or more),   (B-2) a spacer sequence of SEQ ID NO: 29,   (B-3) a first T-cell stimulatory cytokine that is IL-2 of SEQ ID NO: 25 (or a sequence having an amino acid sequence identity thereto of 80% or more, preferably 90% or more, more preferably 95% or more, still more preferably 98% or more, and further still more preferably 99% or more),   (B-4) a spacer sequence of SEQ ID NO: 29, and   (B-5) a partial sequence of a tetraspanin of SEQ ID NO: 59 (or a sequence having an amino acid sequence identity thereto of 80% or more, preferably 90% or more, more preferably 95% or more, still more preferably 98% or more, and further still more preferably 99% or more),       

     the fusion protein being capable of presenting the first T-cell stimulatory cytokine outside membrane; and 
     (C) a fusion protein of which an amino acid sequence consists of, from an N-terminal side thereof,
         (C-1) a T-cell costimulatory molecule that is CD80 of SEQ ID NO: 67 (or a sequence having an amino acid sequence identity thereto of 80% or more, preferably 90% or more, more preferably 95% or more, still more preferably 98% or more, and further still more preferably 99% or more), and   (C-3) a tetraspanin of SEQ ID NO: 21 (or a sequence having an amino acid sequence identity thereto of 80% or more, preferably 90% or more, more preferably 95% or more, still more preferably 98% or more, and further still more preferably 99% or more),       

     the fusion protein being capable of allowing the T-cell costimulatory molecule to interact with T cells. 
     In an embodiment of the present invention, the antigen-presenting extracellular vesicle described in the present specification is an antigen-presenting extracellular vesicle the membrane of which contains: 
     (A) a fusion protein of which an amino acid sequence consists of, from an N-terminal side thereof,
         (A-1) an MHC class I molecule-restricted antigen peptide,   (A-2) a spacer sequence of SEQ ID NO: 5,   (A-3) a single chain MHC class I molecule of SEQ ID NO: 65 (or a sequence having an amino acid sequence identity thereto of 80% or more, preferably 90% or more, more preferably 95% or more, still more preferably 98% or more, and further still more preferably 99% or more), and   (A-5) a tetraspanin of SEQ ID NO: 15 (or a sequence having an amino acid sequence identity thereto of 80% or more, preferably 90% or more, more preferably 95% or more, still more preferably 98% or more, and further still more preferably 99% or more),       

     the fusion protein capable of presenting an antigen peptide outside membrane; 
     (B) a fusion protein capable of presenting the first T-cell stimulatory cytokine of SEQ ID NO: 31 (or a sequence having an amino acid sequence identity thereto of 80% or more, preferably 90% or more, more preferably 95% or more, still more preferably 98% or more, and further still more preferably 99% or more), outside membrane; and 
     (C) a fusion protein capable of allowing the T-cell costimulatory molecule of SEQ ID NO: 69 (or a sequence having an amino acid sequence identity thereto of 80% or more, preferably 90% or more, more preferably 95% or more, still more preferably 98% or more, and further still more preferably 99% or more), to interact with T cells. 
     In an embodiment of the present invention, the antigen-presenting extracellular vesicle described in the present specification is an antigen-presenting extracellular vesicle the membrane of which contains: 
     (A) a protein complex capable of presenting an antigen peptide outside membrane, in which the protein complex contains: 
     a fusion protein of which an amino acid sequence consists of, from an N-terminal side thereof,
         (A-1) an MHC class II molecule-restricted antigen peptide,   (A-2) a spacer sequence of SEQ ID NO: 39,   (A-3) an MHC class IIβ chain of SEQ ID NO: 37 (or a sequence having an amino acid sequence identity thereto of 80% or more, preferably 90% or more, more preferably 95% or more, still more preferably 98% or more, and further still more preferably 99% or more), and   (A-5) a tetraspanin of SEQ ID NO: 15 (or a sequence having an amino acid sequence identity thereto of 80% or more, preferably 90% or more, more preferably 95% or more, still more preferably 98% or more, and further still more preferably 99% or more);       

     and
         (A-6) an MHC class IIα chain of SEQ ID NO: 71 (or a sequence having an amino acid sequence identity thereto of 80% or more, preferably 90% or more, more preferably 95% or more, still more preferably 98% or more, and further still more preferably 99% or more);       

     (B) a fusion protein of which an amino acid sequence consists of, from an N-terminal side thereof,
         (B-1) a partial sequence of a tetraspanin of SEQ ID NO: 57 (or a sequence having an amino acid sequence identity thereto of 80% or more, preferably 90% or more, more preferably 95% or more, still more preferably 98% or more, and further still more preferably 99% or more),   (B-2) a spacer sequence of SEQ ID NO: 29,   (B-3) a first T-cell stimulatory cytokine that is IL-2 of SEQ ID NO: 25 (or a sequence having an amino acid sequence identity thereto of 80% or more, preferably 90% or more, more preferably 95% or more, still more preferably 98% or more, and further still more preferably 99% or more),   (B-4) a spacer sequence of SEQ ID NO: 29, and   (B-5) a partial sequence of a tetraspanin of SEQ ID NO: 59 (or a sequence having an amino acid sequence identity thereto of 80% or more, preferably 90% or more, more preferably 95% or more, still more preferably 98% or more, and further still more preferably 99% or more),       

     the fusion protein being capable of presenting the first T-cell stimulatory cytokine outside membrane; and 
     (C) a fusion protein of which an amino acid sequence consists of, from an N-terminal side thereof,
         (C-1) a T-cell costimulatory molecule that is CD80 of SEQ ID NO: 67 (or a sequence having an amino acid sequence identity thereto of 80% or more, preferably 90% or more, more preferably 95% or more, still more preferably 98% or more, and further still more preferably 99% or more), and   (C-3) a tetraspanin of SEQ ID NO: 21 (or a sequence having an amino acid sequence identity thereto of 80% or more, preferably 90% or more, more preferably 95% or more, still more preferably 98% or more, and further still more preferably 99% or more),       

     the fusion protein being capable of allowing the T-cell costimulatory molecule to interact with T cells. 
     In an embodiment of the present invention, the antigen-presenting extracellular vesicle described in the present specification is an antigen-presenting extracellular vesicle the membrane of which contains: 
     (A) a protein complex capable of presenting an antigen peptide outside membrane, in which the protein complex contains: 
     a fusion protein of which an amino acid sequence consists of, from an N-terminal side thereof,
         (A-1) an MHC class II molecule-restricted antigen peptide,   (A-2) a spacer sequence of SEQ ID NO: 39,   (A-3) an MHC class HP chain of SEQ ID NO: 37 (or a sequence having an amino acid sequence identity thereto of 80% or more, preferably 90% or more, more preferably 95% or more, still more preferably 98% or more, and further still more preferably 99% or more), and   (A-5) a tetraspanin of SEQ ID NO: 15 (or a sequence having an amino acid sequence identity thereto of 80% or more, preferably 90% or more, more preferably 95% or more, still more preferably 98% or more, and further still more preferably 99% or more);       

     and
         (A-6) an MHC class IIα chain of SEQ ID NO: 71 (or a sequence having an amino acid sequence identity thereto of 80% or more, preferably 90% or more, more preferably 95% or more, still more preferably 98% or more, and further still more preferably 99% or more);       

     (B) a fusion protein capable of presenting the first T-cell stimulatory cytokine of SEQ ID NO: 31 (or a sequence having an amino acid sequence identity thereto of 80% or more, preferably 90% or more, more preferably 95% or more, still more preferably 98% or more, and further still more preferably 99% or more), outside membrane; and 
     (C) a fusion protein capable of allowing the T-cell costimulatory molecule of SEQ ID NO: 69 (or a sequence having an amino acid sequence identity thereto of 80% or more, preferably 90% or more, more preferably 95% or more, still more preferably 98% or more, and further still more preferably 99% or more), to interact with T cells. 
     In an embodiment of the present invention, the antigen-presenting extracellular vesicle described in the present specification is an antigen-presenting extracellular vesicle the membrane of which contains: 
     (A) a protein complex capable of presenting an antigen peptide outside membrane, in which the protein complex contains: 
     a fusion protein of which an amino acid sequence consists of, from an N-terminal side thereof,
         (A-1) an MHC class II molecule-restricted antigen peptide,   (A-2) a spacer sequence of SEQ ID NO: 39,   (A-3) an MHC class IIβ chain of SEQ ID NO: 37 (or a sequence having an amino acid sequence identity thereto of 80% or more, preferably 90% or more, more preferably 95% or more, still more preferably 98% or more, and further still more preferably 99% or more), and   (A-5) a tetraspanin of SEQ ID NO: 15 (or a sequence having an amino acid sequence identity thereto of 80% or more, preferably 90% or more, more preferably 95% or more, still more preferably 98% or more, and further still more preferably 99% or more);       

     and
         (A-6) an MHC class IIα chain of SEQ ID NO: 71 (or a sequence having an amino acid sequence identity thereto of 80% or more, preferably 90% or more, more preferably 95% or more, still more preferably 98% or more, and further still more preferably 99% or more);       

     (B) a fusion protein of which an amino acid sequence consists of, from an N-terminal side thereof,
         (B-1) a partial sequence of a tetraspanin of SEQ ID NO: 57 (or a sequence having an amino acid sequence identity thereto of 80% or more, preferably 90% or more, more preferably 95% or more, still more preferably 98% or more, and further still more preferably 99% or more),   (B-2) a spacer sequence of SEQ ID NO: 29,   (B-3) a first T-cell stimulatory cytokine that is IL-2 of SEQ ID NO: 25 (or a sequence having an amino acid sequence identity thereto of 80% or more, preferably 90% or more, more preferably 95% or more, still more preferably 98% or more, and further still more preferably 99% or more),   (B-4) a spacer sequence of SEQ ID NO: 29, and   (B-5) a partial sequence of a tetraspanin of SEQ ID NO: 59 (or a sequence having an amino acid sequence identity thereto of 80% or more, preferably 90% or more, more preferably 95% or more, still more preferably 98% or more, and further still more preferably 99% or more),       

     the fusion protein being capable of presenting the first T-cell stimulatory cytokine outside membrane; 
     (B′) a fusion protein of which an amino acid sequence consists of, from an N-terminal side thereof,
         (B-3) a second T-cell stimulatory cytokine that is TGF-β of SEQ ID NO: 73 (or a sequence having an amino acid sequence identity thereto of 80% or more, preferably 90% or more, more preferably 95% or more, still more preferably 98% or more, and further still more preferably 99% or more),   (B-4) a spacer sequence of SEQ ID NO: 29, and   (B-5) MFG-E8 of SEQ ID NO: 49 (or a sequence having an amino acid sequence identity thereto of 80% or more, preferably 90% or more, more preferably 95% or more, still more preferably 98% or more, and further still more preferably 99% or more),       

     the fusion protein being capable of presenting the second T-cell stimulatory cytokine outside membrane; and 
     (C) a fusion protein of which an amino acid sequence consists of, from an N-terminal side thereof,
         (C-1) a T-cell costimulatory molecule that is CD80 of SEQ ID NO: 67 (or a sequence having an amino acid sequence identity thereto of 80% or more, preferably 90% or more, more preferably 95% or more, still more preferably 98% or more, and further still more preferably 99% or more), and   (C-3) a tetraspanin of SEQ ID NO: 21 (or a sequence having an amino acid sequence identity thereto of 80% or more, preferably 90% or more, more preferably 95% or more, still more preferably 98% or more, and further still more preferably 99% or more),       

     the fusion protein being capable of allowing the T-cell costimulatory molecule to interact with T cells. 
     In an embodiment of the present invention, the antigen-presenting extracellular vesicle described in the present specification is an antigen-presenting extracellular vesicle the membrane of which contains: 
     (A) a protein complex capable of presenting an antigen peptide outside membrane, in which the protein complex contains: 
     a fusion protein of which an amino acid sequence consists of, from an N-terminal side thereof,
         (A-1) an MHC class II molecule-restricted antigen peptide,   (A-2) a spacer sequence of SEQ ID NO: 39,   (A-3) an MHC class IIβ chain of SEQ ID NO: 37 (or a sequence having an amino acid sequence identity thereto of 80% or more, preferably 90% or more, more preferably 95% or more, still more preferably 98% or more, and further still more preferably 99% or more),   (A-5) a tetraspanin of SEQ ID NO: 15 (or a sequence having an amino acid sequence identity thereto of 80% or more, preferably 90% or more, more preferably 95% or more, still more preferably 98% or more, and further still more preferably 99% or more);       

     and
         (A-6) an MHC class IIα chain of SEQ ID NO: 71 (or a sequence having an amino acid sequence identity thereto of 80% or more, preferably 90% or more, more preferably 95% or more, still more preferably 98% or more, and further still more preferably 99% or more);       

     (B) a fusion protein capable of presenting the first T-cell stimulatory cytokine of SEQ ID NO: 31 (or a sequence having an amino acid sequence identity thereto of 80% or more, preferably 90% or more, more preferably 95% or more, still more preferably 98% or more, and further still more preferably 99% or more), outside membrane; 
     (B′) a fusion protein capable of presenting the second T-cell stimulatory cytokine of SEQ ID NO: 75 (or a sequence having an amino acid sequence identity thereto of 80% or more, preferably 90% or more, more preferably 95% or more, still more preferably 98% or more, and further still more preferably 99% or more), outside membrane; and 
     (C) a fusion protein capable of allowing the T-cell costimulatory molecule of SEQ ID NO: 69 (or a sequence having an amino acid sequence identity thereto of 80% or more, preferably 90% or more, more preferably 95% or more, still more preferably 98% or more, and further still more preferably 99% or more), to interact with T cells. 
     In an embodiment of the present invention, the antigen-presenting extracellular vesicle described in the present specification is an antigen-presenting extracellular vesicle the membrane of which contains: 
     (A) a protein complex capable of presenting an antigen peptide outside membrane, in which the protein complex contains: 
     a fusion protein of which an amino acid sequence consists of, from an N-terminal side thereof,
         (A-1) an MHC class II molecule-restricted antigen peptide,   (A-2) a spacer sequence of SEQ ID NO: 39,   (A-3) an MHC class IIβ chain of SEQ ID NO: 37 (or a sequence having an amino acid sequence identity thereto of 80% or more, preferably 90% or more, more preferably 95% or more, still more preferably 98% or more, and further still more   (A-5) a tetraspanin of SEQ ID NO: 15 (or a sequence having an amino acid sequence identity thereto of 80% or more, preferably 90% or more, more preferably 95% or more, still more preferably 98% or more, and further still more preferably 99% or more);       

     and
         (A-6) an MHC class IIα chain of SEQ ID NO: 71 (or a sequence having an amino acid sequence identity thereto of 80% or more, preferably 90% or more, more preferably 95% or more, still more preferably 98% or more, and further still more preferably 99% or more);       

     (B) a fusion protein of which an amino acid sequence consists of, from an N-terminal side thereof,
         (B-1) a partial sequence of a tetraspanin of SEQ ID NO: 61 (or a sequence having an amino acid sequence identity thereto of 80% or more, preferably 90% or more, more preferably 95% or more, still more preferably 98% or more, and further still more preferably 99% or more),   (B-2) a spacer sequence of SEQ ID NO: 29,   (B-3) a first T-cell stimulatory cytokine that is IL-4 of SEQ ID NO: 53 (or a sequence having an amino acid sequence identity thereto of 80% or more, preferably 90% or more, more preferably 95% or more, still more preferably 98% or more, and further still more preferably 99% or more),   (B-4) a spacer sequence of SEQ ID NO: 29, and   (B-5) a partial sequence of a tetraspanin of SEQ ID NO: 63 (or a sequence having an amino acid sequence identity thereto of 80% or more, preferably 90% or more, more preferably 95% or more, still more preferably 98% or more, and further still more preferably 99% or more),       

     the fusion protein being capable of presenting the first T-cell stimulatory cytokine outside membrane; and 
     (C) a fusion protein of which an amino acid sequence consists of, from an N-terminal side thereof,
         (C-1) a T-cell costimulatory molecule that is CD80 of SEQ ID NO: 67 (or a sequence having an amino acid sequence identity thereto of 80% or more, preferably 90% or more, more preferably 95% or more, still more preferably 98% or more, and further still more preferably 99% or more), and   (C-3) a tetraspanin of SEQ ID NO: 21 (or a sequence having an amino acid sequence identity thereto of 80% or more, preferably 90% or more, more preferably 95% or more, still more preferably 98% or more, and further still more preferably 99% or more),       

     the fusion protein being capable of allowing the T-cell costimulatory molecule to interact with T cells. 
     In an embodiment of the present invention, the antigen-presenting extracellular vesicle described in the present specification is an antigen-presenting extracellular vesicle the membrane of which contains: 
     (A) a protein complex capable of presenting an antigen peptide outside membrane, in which the protein complex contains: 
     a fusion protein of which an amino acid sequence consists of, from an N-terminal side thereof,
         (A-1) an MHC class II molecule-restricted antigen peptide,   (A-2) a spacer sequence of SEQ ID NO: 39,   (A-3) an MHC class IIβ chain of SEQ ID NO: 37 (or a sequence having an amino acid sequence identity thereto of 80% or more, preferably 90% or more, more preferably 95% or more, still more preferably 98% or more, and further still more preferably 99% or more), and   (A-5) a tetraspanin of SEQ ID NO: 15 (or a sequence having an amino acid sequence identity thereto of 80% or more, preferably 90% or more, more preferably 95% or more, still more preferably 98% or more, and further still more preferably 99% or more);       

     and
         (A-6) an MHC class IIα chain of SEQ ID NO: 71 (or a sequence having an amino acid sequence identity thereto of 80% or more, preferably 90% or more, more preferably 95% or more, still more preferably 98% or more, and further still more preferably 99% or more);       

     (B) a fusion protein capable of presenting the first T-cell stimulatory cytokine of SEQ ID NO: 55 (or a sequence having an amino acid sequence identity thereto of 80% or more, preferably 90% or more, more preferably 95% or more, still more preferably 98% or more, and further still more preferably 99% or more), outside membrane; and 
     (C) a fusion protein capable of allowing the T-cell costimulatory molecule of SEQ ID NO: 69 (or a sequence having an amino acid sequence identity thereto of 80% or more, preferably 90% or more, more preferably 95% or more, still more preferably 98% or more, and further still more preferably 99% or more), to interact with T cells. 
     In an embodiment of the present invention, as for the (A), (B), and (C) above, (A) and (B) may be fused to form one molecule, (B) and (C) may be fused to form one molecule, and (A), (B), and (C) are fused to form one molecule. Such a fusion molecule may be translated as one protein molecule with or without a spacer sequence between (A), (B), and (C), or the proteins of (A), (B), and (C) may be fused by chemical crosslinking (for example, a disulfide bond between cysteine residues) to form one molecule. 
     Alternatively, the (A), (B), and (C) above may be functionally fused by sharing an element for localizing the proteins thereof in the extracellular vesicle, that is, a site of a “membrane protein capable of being expressed in membrane of an extracellular vesicle or a transmembrane domain thereof” or a “protein capable of binding to membrane of an extracellular vesicle or a domain thereof”. 
     For example, in an embodiment of the present invention, 
     the antigen-presenting extracellular vesicle may also contain (D) a fusion protein comprising: 
     (1) an antigen-presenting MHC molecule; 
     (2) at least one T-cell stimulatory cytokine; and 
     (3) a “membrane protein capable of being expressed in membrane of an extracellular vesicle or a transmembrane domain thereof” or a “protein capable of binding to membrane of an extracellular vesicle or a domain thereof”, 
     the fusion protein being fused in a form of sharing the site of the “membrane protein capable of being expressed in membrane of an extracellular vesicle or the transmembrane domain thereof” or the “protein capable of binding to membrane of an extracellular vesicle or the domain thereof” in (A) and (B); 
     a fusion protein (F) comprising: 
     (1) an antigen-presenting MHC molecule; 
     (2) a T-cell costimulatory molecule; and 
     (3) a “membrane protein capable of being expressed in membrane of an extracellular vesicle or a transmembrane domain thereof” or a “protein capable of binding to membrane of an extracellular vesicle or a domain thereof”, 
     the fusion protein being fused in a form of sharing the site of the “membrane protein capable of being expressed in membrane of an extracellular vesicle or the transmembrane domain thereof” or the “protein capable of binding to membrane of an extracellular vesicle or the domain thereof” in (A) and (C); 
     a fusion protein (G) comprising: 
     (1) at least one T-cell stimulatory cytokine; 
     (2) a T-cell costimulatory molecule; and 
     (3) a “membrane protein capable of being expressed in membrane of an extracellular vesicle or a transmembrane domain thereof” or a “protein capable of binding to membrane of an extracellular vesicle or a domain thereof”, 
     the fusion protein being fused in a form of sharing the site of the “membrane protein capable of being expressed in membrane of an extracellular vesicle or the transmembrane domain thereof” or the “protein capable of binding to membrane of an extracellular vesicle or the domain thereof” in (B) and (C); 
     Or, 
     a fusion protein (E) comprising: 
     (1) an antigen-presenting MHC molecule; 
     (2) at least one T-cell stimulatory cytokine; 
     (3) a T-cell costimulatory molecule; and 
     (4) a “membrane protein capable of being expressed in membrane of an extracellular vesicle or a transmembrane domain thereof” or a “protein capable of binding to membrane of an extracellular vesicle or a domain thereof”, 
     the fusion protein being fused in a form of sharing the site of the “membrane protein capable of being expressed in membrane of an extracellular vesicle or the transmembrane domain thereof” or the “protein capable of binding to membrane of an extracellular vesicle or the domain thereof” in (A) to (C). 
     In an embodiment of the present invention, the antigen-presenting extracellular vesicle may be an antigen-presenting extracellular vesicle containing a fusion protein (D) having the functions of the constitutional requirement (A) and the constitutional requirement (B) using the “protein which contains a first T-cell stimulatory cytokine and is capable of presenting the first T-cell stimulatory cytokine outside membrane” of the constitutional requirement (B), instead of the “membrane protein capable of being expressed in membrane of an extracellular vesicle or the transmembrane domain thereof or the protein capable of binding to membrane of an extracellular vesicle” of the constitutional requirement (A). 
     Such a fusion protein (D) having the functions of the constitutional requirement (A) and the constitutional requirement (B) may be 
     (D) a fusion protein which contains an antigen-presenting MHC molecule and at least one T-cell stimulatory cytokine and is capable of presenting the antigen and the T-cell stimulatory cytokine outside membrane. 
     The fusion protein may contain the antigen-presenting MHC molecule, the at least one T-cell stimulatory cytokine, and a membrane protein capable of being localized to membrane of an extracellular vesicle or a transmembrane domain thereof or a protein capable of binding to membrane of an extracellular vesicle or a membrane-binding domain thereof. 
     In the fusion protein (D) having the functions of the constitutional requirement (A) and the constitutional requirement (B), the membrane protein capable of being localized to membrane of an extracellular vesicle or the protein capable of binding to membrane of an extracellular vesicle may be a tetraspanin or MFG-E8. 
     The fusion protein may also comprise an amino acid sequence encoding, from an N-terminal side thereof,
         (D-1) an MHC molecule-restricted antigen peptide,   (D-2) a spacer sequence which may be present,   (D-3) a single chain MHC molecule,   (D-4) a spacer sequence which may be present, and   (D-5) a fusion peptide comprising a tetraspanin or a transmembrane domain thereof or MFG-E8 or a transmembrane domain thereof, and the at least one T-cell stimulatory cytokine, in this order.       

     The fusion protein may also comprise an amino acid sequence encoding, from an N-terminal side thereof,
         (D-1) a fusion peptide comprising a tetraspanin or a transmembrane domain thereof or MFG-E8 or a transmembrane domain thereof, and the at least one T-cell stimulatory cytokine,   (D-2) a spacer sequence which may be optionally present,   (D-3) a single chain MHC molecule,   (D-4) a spacer sequence which may be optionally present, and   (D-5) an MHC molecule-restricted antigen peptide, in this order.       

     Here, the fusion peptide may also comprise an amino acid sequence encoding, from an N-terminal side thereof,
         (1) a partial sequence of a tetraspanin containing a transmembrane domain 1, a small intracellular loop, a transmembrane domain 2, a small extracellular loop, and a transmembrane domain 3,   (2) a spacer sequence which may be optionally present,   (3) the at least one T-cell stimulatory cytokine,   (4) a spacer sequence which may be optionally present, and   (5) a partial sequence of a tetraspanin containing a transmembrane domain 4, in this order.       

     The fusion peptide may also comprise an amino acid sequence encoding, from an N-terminal side thereof,
         (1) the at least one of T-cell stimulatory cytokine,   (2) a spacer sequence which may be optionally present, and   (3) MFG-E8, in this order.       

     In an embodiment of the present invention, the MHC molecule-restricted antigen peptide is an MHC class I molecule-restricted antigen peptide, the single chain MHC molecule may contain an extracellular domain of an MHC class Iα chain, the MHC molecule-restricted antigen peptide is an MHC class II molecule-restricted antigen peptide, and the single chain MHC molecule may contain an extracellular domain of an MHC class IIα chain and/or an extracellular domain of an MHC class IIβ chain. 
     In the aspect containing the fusion protein (D) having the functions of the constitutional requirement (A) and the constitutional requirement (B): 
     (C) a protein which comprises at least one T-cell costimulatory molecule and is capable of allowing the T-cell costimulatory molecule to interact with T cells may be further contained in the membrane; 
     the protein capable of interacting with T cells may also comprises the at least one T-cell costimulatory molecule, and a membrane protein capable of being expressed in membrane of an extracellular vesicle or a transmembrane domain thereof or a protein capable of binding to membrane of an extracellular vesicle or a domain thereof; and 
     the protein capable of interacting with T cells may also comprises the at least one T-cell costimulatory molecule, and a tetraspanin or a transmembrane domain thereof or MFG-E8 or a domain thereof. 
     In an embodiment of the present invention, the extracellular vesicle is an exosome. 
     The antigen-presenting extracellular vesicle in the present specification may contain or be bound to a substance that may be therapeutically beneficial (for example, a low-molecular compound, a nucleic acid, or the like) inside the membrane thereof or in the membrane. Examples of a method for encapsulating the substance inside the membrane of the extracellular vesicle include, but are not limited to, a method in which the substance and the extracellular vesicle described in the present specification are mixed in a suitable solvent. 
     In an embodiment of the present invention, the antigen-presenting extracellular vesicle may contain any protein preparation. The protein preparation is not particularly limited, but may be a protein that can also exist in nature such as erythropoietin, a synthetic protein that does not exist in nature such as an immunoglobulin-CTLA4 fusion protein, or a monoclonal antibody or an active fragment thereof. These protein preparations are fusion proteins with a membrane protein capable of being localized to membrane of an extracellular vesicle or a transmembrane domain thereof or a protein capable of binding to membrane of an extracellular vesicle or a membrane-binding domain thereof, and may be localized on the surface of the antigen-presenting extracellular vesicle. Such an antigen-presenting extracellular vesicle can be prepared by transfecting cells that produce antigen-presenting extracellular vesicles with a vector for expressing a fusion protein. 
     Each fusion protein or protein complex or a protein preparation contained in the membrane of the antigen-presenting extracellular vesicle described in the present specification may comprise one or a plurality of detectable labels. For example, the fusion protein or the protein complex or the protein preparation may be labeled with a specific lipoprotein molecule, a fluorophore, a radioactive material, or an enzyme (for example, peroxidase or phosphatase), or the like by a conventional method. These labels may be linked to the N-terminus or the C-terminus of the fusion protein or the protein complex or the protein preparation, for example, as a constituent element of the fusion protein or the protein complex or the protein preparation. 
     Polynucleotide 
     In an embodiment of the present invention, there is provided a polynucleotide encoding each fusion protein or protein complex in (A) and (B), and (C) present in some cases that are contained in the membrane of the antigen-presenting extracellular vesicle described in the present specification. In an embodiment of the present invention, there is provided a polynucleotide encoding each fusion protein or protein complex in (A) to (G) defined in the present specification. 
     The “polynucleotide” used in the present specification means a single-stranded or double-stranded DNA molecule or RNA molecule, or the like. The polynucleotide includes genomic DNA, cDNA, hnRNA, mRNA, and the like, and all naturally occurring or artificially modified derivatives thereof. The polynucleotide may be linear or cyclic. 
     The polynucleotide encoding each fusion protein or protein complex in (A) to (G) described above can be appropriately determined by those skilled in the art with reference to the amino acid sequence of the fusion protein or protein complex. Note that the amino acid sequence of each fusion protein or protein complex in (A) to (G) can be appropriately determined with reference to the amino acid sequence of each constituent element (for example, in the case of (A), (A-1) to (A-5), and (A-6) in some cases) in each fusion protein or protein complex. Any type of codon can be selected for use in determining a polynucleotide. For example, a polynucleotide may be determined in consideration of a frequency or the like of codons of cells to be transformed using a vector comprising the polynucleotide. 
     To the N-terminus of the polynucleotide encoding each fusion protein or protein complex in (A) to (G) described above, a polynucleotide encoding a signal peptide (signal sequence) may be added, if necessary. 
     As an amino acid sequence of the signal peptide, any amino acid sequence can be used, and for example, the amino acid sequence of the signal peptide may be determined in consideration of an amino acid sequence of a fusion protein to be expressed, and the like. Examples of the polynucleotide encoding a signal peptide include a polynucleotide (for example, SEQ ID NO: 2) encoding a signal peptide (for example, SEQ ID NO: 1) of β 2  microglobulin, a polynucleotide encoding a signal peptide of an MHC class Iα chain, a polynucleotide encoding a signal peptide of an MHC class IIα chain, and a polynucleotide (for example, SEQ ID NO: 34) encoding a signal peptide (for example, SEQ ID NO: 33) of an MHC class IIβ chain. 
     Information on each constituent element (for example, in the case of (A), (A-1) to (A-5), and (A-6) in some cases) of each fusion protein or protein complex in (A) to (G) described above, the amino acid sequence such as a signal peptide, and the polynucleotide encoding them may be appropriately obtained by searching, for example, a database of known literatures, NCBI (http://www.ncbi.nlm.nih.gov/guide/), and the like. In addition, for the amino acid sequence in the partial sequence of the tetraspanin (for example, the partial sequences in (C-1) and (C-5)) and the polynucleotide encoding the amino acid sequence, WO 2016/139354 A may be referred to. 
     In an embodiment of the present invention, there is provided a polynucleotide encoding any one of: 
     (A) a fusion protein capable of presenting an antigen peptide outside membrane, in which the fusion protein comprises an amino acid sequence consisting of, from an N-terminal side thereof,
         (A-1) an MHC molecule-restricted antigen peptide,   (A-2) a spacer sequence which may be optionally present,   (A-3) a single chain MHC molecule,   (A-4) a spacer sequence which may be optionally present, and   (A-5) a tetraspanin, or       

     (A) a fusion protein constituting a protein complex capable of presenting an antigen peptide outside membrane, 
     in which the fusion protein comprises an amino acid sequence consisting of, from an N-terminal side thereof,
         (A-1) an MHC molecule-restricted antigen peptide,   (A-2) a spacer sequence which may be optionally present,   (A-3) an MHC class Iα chain, β 2  microglobulin, an MHC class IIα chain, or an MHC class IIβ chain,   (A-4) a spacer sequence which may be optionally present, and   (A-5) a tetraspanin;       

     (B) a fusion protein comprising an amino acid sequence consisting of, from an N-terminal side thereof,
         (B-1) a partial sequence of a tetraspanin containing, from an N-terminal side thereof, a transmembrane domain 1, a small extracellular loop, a transmembrane domain 2, a small intracellular loop, and a transmembrane domain 3,   (B-2) a spacer sequence which may be optionally present,   (B-3) a first T-cell stimulatory cytokine,   (B-4) a spacer sequence which may be optionally present, and   (B-5) a partial sequence of a tetraspanin containing a transmembrane domain 4,       

     the fusion protein being capable of presenting the first T-cell stimulatory cytokine outside membrane, or 
     (B) a fusion protein comprising an amino acid sequence consisting of, from an N-terminal side thereof,
         (B-3) a first T-cell stimulatory cytokine,   (B-4) a spacer sequence which may be present, and   (B-5) MFG-E8,       

     the fusion protein being capable of presenting the first T-cell stimulatory cytokine outside membrane; and 
     (C) a fusion protein comprising an amino acid sequence consisting of, from an N-terminal side thereof,
         (C-1) a T-cell costimulatory molecule,   (C-2) a spacer sequence which may be present, and   (C-3) a tetraspanin,       

     the fusion protein being capable of allowing the T-cell costimulatory molecule to interact with T cells. 
     In an embodiment of the present invention, there provided a polynucleotide encoding any one of: 
     (A) a fusion protein of which an amino acid sequence consists of, from an N-terminal side thereof,
         (A-1) an MHC class I molecule-restricted antigen peptide,   (A-2) a spacer sequence of SEQ ID NO: 5,   (A-3) a single chain MHC class I molecule of SEQ ID NO: 65 (or a sequence having an amino acid sequence identity thereto of 80% or more, preferably 90% or more, more preferably 95% or more, still more preferably 98% or more, and further still more preferably 99% or more), and   (A-5) a tetraspanin of SEQ ID NO: 15 (or a sequence having an amino acid sequence identity thereto of 80% or more, preferably 90% or more, more preferably 95% or more, still more preferably 98% or more, and further still more preferably 99% or more),       

     the fusion protein being capable of presenting an antigen peptide outside membrane, or 
     (A) a fusion protein of which an amino acid sequence consists of, from an N-terminal side thereof,
         (A-1) an MHC class II molecule-restricted antigen peptide,   (A-2) a spacer sequence of SEQ ID NO: 39,   (A-3) an MHC class IIβ chain of SEQ ID NO: 37 (or a sequence having an amino acid sequence identity thereto of 80% or more, preferably 90% or more, more preferably 95% or more, still more preferably 98% or more, and further still more preferably 99% or more), and   (A-5) a tetraspanin of SEQ ID NO: 15 (or a sequence having an amino acid sequence identity thereto of 80% or more, preferably 90% or more, more preferably 95% or more, still more preferably 98% or more, and further still more preferably 99% or more), the fusion protein constituting a protein complex capable of presenting an antigen peptide outside membrane;       

     (B) a fusion protein of which an amino acid sequence consists of, from an N-terminal side thereof,
         (B-1) a partial sequence of a tetraspanin of SEQ ID NO: 57 (or a sequence having an amino acid sequence identity thereto of 80% or more, preferably 90% or more, more preferably 95% or more, still more preferably 98% or more, and further still more preferably 99% or more),   (B-2) a spacer sequence of SEQ ID NO: 29,   (B-3) a first T-cell stimulatory cytokine that is IL-2 of SEQ ID NO: 25 (or a sequence having an amino acid sequence identity thereto of 80% or more, preferably 90% or more, more preferably 95% or more, still more preferably 98% or more, and further still more preferably 99% or more),   (B-4) a spacer sequence of SEQ ID NO: 29, and   (B-5) a partial sequence of a tetraspanin of SEQ ID NO: 59 (or a sequence having an amino acid sequence identity thereto of 80% or more, preferably 90% or more, more preferably 95% or more, still more preferably 98% or more, and further still more preferably 99% or more),       

     the fusion protein being capable of presenting the first T-cell stimulatory cytokine outside membrane, 
     (B) a fusion protein of which an amino acid sequence consists of, from an N-terminal side thereof,
         (B-1) a partial sequence of a tetraspanin of SEQ ID NO: 61 (or a sequence having an amino acid sequence identity thereto of 80% or more, preferably 90% or more, more preferably 95% or more, still more preferably 98% or more, and further still more preferably 99% or more),   (B-2) a spacer sequence of SEQ ID NO: 29,   (B-3) a first T-cell stimulatory cytokine that is IL-4 of SEQ ID NO: 53 (or a sequence having an amino acid sequence identity thereto of 80% or more, preferably 90% or more, more preferably 95% or more, still more preferably 98% or more, and further still more preferably 99% or more),   (B-4) a spacer sequence of SEQ ID NO: 29, and   (B-5) a partial sequence of a tetraspanin of SEQ ID NO: 63 (or a sequence having an amino acid sequence identity thereto of 80% or more, preferably 90% or more, more preferably 95% or more, still more preferably 98% or more, and further still more preferably 99% or more),       

     the fusion protein being capable of presenting the first T-cell stimulatory cytokine outside membrane, or 
     (B′) a fusion protein of which an amino acid sequence consists of, from an N-terminal side thereof,
         (B-3) a second T-cell stimulatory cytokine that is TGF-β of SEQ ID NO: 73 (or a sequence having an amino acid sequence identity thereto of 80% or more, preferably 90% or more, more preferably 95% or more, still more preferably 98% or more, and further still more preferably 99% or more),   (B-4) a spacer sequence of SEQ ID NO: 29, and   (B-5) MFG-E8 of SEQ ID NO: 49 (or a sequence having an amino acid sequence identity thereto of 80% or more, preferably 90% or more, more preferably 95% or more, still more preferably 98% or more, and further still more preferably 99% or more),       

     the fusion protein being capable of presenting the second (or first) T-cell stimulatory cytokine outside membrane; and 
     (C) a fusion protein of which an amino acid sequence consists of, from an N-terminal side thereof,
         (C-1) a T-cell costimulatory molecule that is CD80 of SEQ ID NO: 67 (or a sequence having an amino acid sequence identity thereto of 80% or more, preferably 90% or more, more preferably 95% or more, still more preferably 98% or more, and further still more preferably 99% or more), and   (C-3) a tetraspanin of SEQ ID NO: 21 (or a sequence having an amino acid sequence identity thereto of 80% or more, preferably 90% or more, more preferably 95% or more, still more preferably 98% or more, and further still more preferably 99% or more),       

     the fusion protein being capable of allowing the T-cell costimulatory molecule to interact with T cells. 
     In an embodiment of the present invention, a polynucleotide encoding any one of: 
     (A) a fusion protein of which an amino acid sequence consists of, from an N-terminal side thereof,
         (A-1) an MHC class I molecule-restricted antigen peptide,   (A-2) a spacer sequence of SEQ ID NO: 5,   (A-3) a single chain MHC class I molecule of SEQ ID NO: 65 (or a sequence having an amino acid sequence identity thereto of 80% or more, preferably 90% or more, more preferably 95% or more, still more preferably 98% or more, and further still more preferably 99% or more), and   (A-5) a tetraspanin of SEQ ID NO: 15 (or a sequence having an amino acid sequence identity thereto of 80% or more, preferably 90% or more, more preferably 95% or more, still more preferably 98% or more, and further still more preferably 99% or more),       

     the fusion protein being capable of presenting an antigen peptide outside membrane, or 
     (A) a fusion protein of which an amino acid sequence consists of, from an N-terminal side thereof,
         (A-1) an MHC class II molecule-restricted antigen peptide,   (A-2) a spacer sequence of SEQ ID NO: 39,   (A-3) an MHC class IIβ chain of SEQ ID NO: 37 (or a sequence having an amino acid sequence identity thereto of 80% or more, preferably 90% or more, more preferably 95% or more, still more preferably 98% or more, and further still more preferably 99% or more), and   (A-5) a tetraspanin of SEQ ID NO: 15 (or a sequence having an amino acid sequence identity thereto of 80% or more, preferably 90% or more, more preferably 95% or more, still more preferably 98% or more, and further still more preferably 99% or more), the fusion protein constituting a protein complex capable of presenting an antigen peptide outside membrane;       

     (B) a fusion protein capable of presenting the first (or second) T-cell stimulatory cytokine of SEQ ID NO: 31, 75, or 55 (or a sequence having an amino acid sequence identity thereto of 80% or more, preferably 90% or more, more preferably 95% or more, still more preferably 98% or more, and further still more preferably 99% or more), outside membrane; and 
     (C) a fusion protein capable of allowing the T-cell costimulatory molecule of SEQ ID NO: 23 (or a sequence having an amino acid sequence identity thereto of 80% or more, preferably 90% or more, more preferably 95% or more, still more preferably 98% or more, and further still more preferably 99% or more), to interact with T cells. 
     In an embodiment of the present invention, there are provided polynucleotides including: 
     (A) a polynucleotide encoding a fusion protein capable of presenting an antigen peptide outside membrane, in which the polynucleotide comprises a sequence consisting of,
         (A-1) a polynucleotide encoding an MHC class I molecule-restricted antigen peptide,   (A-2) a spacer sequence of SEQ ID NO: 6,   (A-3) a single chain MHC class I molecule of SEQ ID NO: 66 (or a sequence having a sequence identity thereto of 80% or more, preferably 90% or more, more preferably 95% or more, still more preferably 98% or more, and further still more preferably 99% or more), and   (A-5) a tetraspanin of SEQ ID NO: 16 (or a sequence having a sequence identity thereto of 80% or more, preferably 90% or more, more preferably 95% or more, still more preferably 98% or more, and further still more preferably 99% or more), or       

     (A) a polynucleotide encoding a fusion protein constituting a protein complex capable of presenting an antigen peptide outside membrane, in which the polynucleotide comprises a sequence consisting of,
         (A-1) a polynucleotide encoding an MHC class II molecule-restricted antigen peptide,   (A-2) a spacer sequence of SEQ ID NO: 40,   (A-3) an MHC class IIβ chain of SEQ ID NO: 38 (or a sequence having a sequence identity thereto of 80% or more, preferably 90% or more, more preferably 95% or more, still more preferably 98% or more, and further still more preferably 99% or more), and   (A-5) a tetraspanin of SEQ ID NO: 16 (or a sequence having a sequence identity thereto of 80% or more, preferably 90% or more, more preferably 95% or more, still more preferably 98% or more, and further still more preferably 99% or more);       

     (B) a polynucleotide encoding a fusion protein capable of presenting a first T-cell stimulatory cytokine outside membrane, in which the polynucleotide comprises a sequence consisting of,
         (B-1) a partial sequence of a tetraspanin of SEQ ID NO: 58 (or a sequence having a sequence identity thereto of 80% or more, preferably 90% or more, more preferably 95% or more, still more preferably 98% or more, and further still more preferably 99% or more),   (B-2) a spacer sequence of SEQ ID NO: 30,   (B-3) a first T-cell stimulatory cytokine that is IL-2 of SEQ ID NO: 26 (or a sequence having a sequence identity thereto of 80% or more, preferably 90% or more, more preferably 95% or more, still more preferably 98% or more, and further still more preferably 99% or more),   (B-4) a spacer sequence of SEQ ID NO: 30, and   (B-5) a partial sequence of a tetraspanin of SEQ ID NO: 60 (or a sequence having a sequence identity thereto of 80% or more, preferably 90% or more, more preferably 95% or more, still more preferably 98% or more, and further still more preferably 99% or more),       

     (B) a polynucleotide encoding a fusion protein capable of presenting a first T-cell stimulatory cytokine outside membrane, in which the polynucleotide comprises a sequence consisting of,
         (B-1) a partial sequence of a tetraspanin of SEQ ID NO: 62 (or a sequence having a sequence identity thereto of 80% or more, preferably 90% or more, more preferably 95% or more, still more preferably 98% or more, and further still more preferably 99% or more),   (B-2) a spacer sequence of SEQ ID NO: 30,   (B-3) a first T-cell stimulatory cytokine that is IL-4 of SEQ ID NO: 54 (or a sequence having a sequence identity thereto of 80% or more, preferably 90% or more, more preferably 95% or more, still more preferably 98% or more, and further still more preferably 99% or more),   (B-4) a spacer sequence of SEQ ID NO: 30, and   (B-5) a partial sequence of a tetraspanin of SEQ ID NO: 64 (or a sequence having a sequence identity thereto of 80% or more, preferably 90% or more, more preferably 95% or more, still more preferably 98% or more, and further still more preferably 99% or more), or       

     (B′) a polynucleotide encoding a fusion protein capable of presenting a second (or first) T-cell stimulatory cytokine outside membrane, in which the polynucleotide comprises a sequence consisting of,
         (B-3) a second (or first) T-cell stimulatory cytokine that is TGF-β of SEQ ID NO: 74 (or a sequence having a sequence identity thereto of 80% or more, preferably 90% or more, more preferably 95% or more, still more preferably 98% or more, and further still more preferably 99% or more),   (B-4) a spacer sequence of SEQ ID NO: 30, and   (B-5) MFG-E8 of SEQ ID NO: 50 (or a sequence having a sequence identity thereto of 80% or more, preferably 90% or more, more preferably 95% or more, still more preferably 98% or more, and further still more preferably 99% or more); and       

     (C) a polynucleotide encoding a fusion protein capable of allowing the T-cell costimulatory molecule to interact with T cells, in which the polynucleotide comprises a sequence consisting of,
         (C-1) a T-cell costimulatory molecule that is CD80 of SEQ ID NO: 68 (or a sequence having a sequence identity thereto of 80% or more, preferably 90% or more, more preferably 95% or more, still more preferably 98% or more, and further still more preferably 99% or more), and   (C-3) a tetraspanin of SEQ ID NO: 22 (or a sequence having a sequence identity thereto of 80% or more, preferably 90% or more, more preferably 95% or more, still more preferably 98% or more, and further still more preferably 99% or more).       

     In an embodiment of the present invention, there is provided a polynucleotide encoding: 
     (A) a polynucleotide encoding a fusion protein capable of presenting an antigen peptide outside membrane, in which the polynucleotide comprises a sequence consisting of,
         (A-1) a polynucleotide encoding an MHC class I molecule-restricted antigen peptide,   (A-2) a spacer sequence of SEQ ID NO: 6,   (A-3) a single chain MHC class I molecule of SEQ ID NO: 66 (or a sequence having a sequence identity thereto of 80% or more, preferably 90% or more, more preferably 95% or more, still more preferably 98% or more, and further still more preferably 99% or more), and   (A-5) a tetraspanin of SEQ ID NO: 16 (or a sequence having a sequence identity thereto of 80% or more, preferably 90% or more, more preferably 95% or more, still more preferably 98% or more, and further still more preferably 99% or more), or       

     (A) a polynucleotide encoding a fusion protein constituting a protein complex capable of presenting an antigen peptide outside membrane, in which the polynucleotide comprises a sequence consisting of,
         (A-1) a polynucleotide encoding an MHC class II molecule-restricted antigen peptide,   (A-2) a spacer sequence of SEQ ID NO: 40,   (A-3) an MHC class IIβ chain of SEQ ID NO: 38 (or a sequence having a sequence identity thereto of 80% or more, preferably 90% or more, more preferably 95% or more, still more preferably 98% or more, and further still more preferably 99% or more), and   (A-5) a tetraspanin of SEQ ID NO: 16 (or a sequence having a sequence identity thereto of 80% or more, preferably 90% or more, more preferably 95% or more, still more preferably 98% or more, and further still more preferably 99% or more);       

     (B) a polynucleotide encoding a fusion protein capable of presenting the first (or second) T-cell stimulatory cytokine of SEQ ID NO: 32, 76, or 56 (or a sequence having a sequence identity thereto of 80% or more, preferably 90% or more, more preferably 95% or more, still more preferably 98% or more, and further still more preferably 99% or more), outside membrane; or 
     (C) a polynucleotide encoding a fusion protein capable of allowing the T-cell costimulatory molecule of SEQ ID NO: 24 (or a sequence having a sequence identity thereto of 80% or more, preferably 90% or more, more preferably 95% or more, still more preferably 98% or more, and further still more preferably 99% or more), to interact with T cells. 
     In an embodiment of the present invention, as for the (A), (B), and (C) above, (A) and (B) may be fused to form a polynucleotide encoding fusion proteins to be one molecule, (B) and (C) may be fused to form a polynucleotide encoding fusion proteins to be one molecule, and (A), (B), and (C) may be fused to form a polynucleotide encoding fusion proteins to be one molecule. Such a polynucleotide may encode one fusion protein with or without a spacer sequence between (A), (B), and (C). 
     Alternatively, the polynucleotide in an embodiment of the present invention may encode a fusion protein obtained by functionally fusing the (A), (B), and (C) above by sharing an element for localizing the proteins thereof in the extracellular vesicle, that is, a site of a “membrane protein capable of being expressed in membrane of an extracellular vesicle or a transmembrane domain thereof” or a “protein capable of binding to membrane of an extracellular vesicle or a domain thereof”. 
     For example, in an embodiment of the present invention, the polynucleotide may be a polynucleotide encoding (D) a fusion protein comprising: 
     (1) an antigen-presenting MHC molecule; 
     (2) at least one T-cell stimulatory cytokine; and 
     (3) a “membrane protein capable of being expressed in membrane of an extracellular vesicle or a transmembrane domain thereof” or a “protein capable of binding to membrane of an extracellular vesicle or a domain thereof”, 
     the fusion protein being fused in a form of sharing the site of the “membrane protein capable of being expressed in membrane of an extracellular vesicle or the transmembrane domain thereof” or the “protein capable of binding to membrane of an extracellular vesicle or the domain thereof” in (A) and (B); 
     a polynucleotide encoding a fusion protein (F) containing: 
     (1) an antigen-presenting MHC molecule; 
     (2) a T-cell costimulatory molecule; and 
     (3) a “membrane protein capable of being expressed in membrane of an extracellular vesicle or a transmembrane domain thereof” or a “protein capable of binding to membrane of an extracellular vesicle or a domain thereof”, 
     the fusion protein being fused in a form of sharing the site of the “membrane protein capable of being expressed in membrane of an extracellular vesicle or the transmembrane domain thereof” or the “protein capable of binding to membrane of an extracellular vesicle or the domain thereof” in (A) and (C); 
     a polynucleotide encoding a fusion protein (G) containing: 
     (1) at least one T-cell stimulatory cytokine; 
     (2) a T-cell costimulatory molecule; and 
     (3) a “membrane protein capable of being expressed in membrane of an extracellular vesicle or a transmembrane domain thereof” or a “protein capable of binding to membrane of an extracellular vesicle or a domain thereof”, 
     the fusion protein being fused in a form of sharing the site of the “membrane protein capable of being expressed in membrane of an extracellular vesicle or the transmembrane domain thereof” or the “protein capable of binding to membrane of an extracellular vesicle or the domain thereof” in (B) and (C); 
     or, 
     a polynucleotide encoding a fusion protein (E) containing: 
     (1) an antigen-presenting MHC molecule; 
     (2) at least one T-cell stimulatory cytokine; 
     (2) a T-cell costimulatory molecule; and 
     (4) a “membrane protein capable of being expressed in membrane of an extracellular vesicle or a transmembrane domain thereof” or a “protein capable of binding to membrane of an extracellular vesicle or a domain thereof”, 
     the fusion protein being fused in a form of sharing the site of the “membrane protein capable of being expressed in membrane of an extracellular vesicle or the transmembrane domain thereof” or the “protein capable of binding to membrane of an extracellular vesicle or the domain thereof” in (A) to (C). 
     In an embodiment of the present invention, the polynucleotide may be a polynucleotide encoding a fusion protein which contains an antigen-presenting MHC molecule and at least one T-cell stimulatory cytokine and is capable of presenting the antigen and the T-cell stimulatory cytokine, the fusion protein being the fusion protein (D) having the functions of the constitutional requirement (A) and the constitutional requirement (B) using the protein of the constitutional requirement (B) which contains a first T-cell stimulatory cytokine and is capable of presenting the first T-cell stimulatory cytokine outside membrane, instead of the membrane protein capable of being expressed in membrane of an extracellular vesicle or the transmembrane domain thereof or the protein capable of binding to membrane of an extracellular vesicle of the constitutional requirement (A). 
     Such a fusion protein (D) having the functions of the constitutional requirement (A) and the constitutional requirement (B) may be a fusion protein which contains an antigen-presenting MHC molecule and at least one T-cell stimulatory cytokine and is capable of presenting the antigen and the T-cell stimulatory cytokine outside membrane. 
     The fusion protein may comprise the antigen-presenting MHC molecule, the at least one T-cell stimulatory cytokine, and a membrane protein capable of being localized to membrane of an extracellular vesicle or a transmembrane domain thereof or a protein capable of binding to membrane of an extracellular vesicle or a membrane-binding domain thereof. 
     In the fusion protein (D) having the functions of the constitutional requirement (A) and the constitutional requirement (B), the membrane protein capable of being localized to membrane of an extracellular vesicle or the protein capable of binding to membrane of an extracellular vesicle may be a tetraspanin or MFG-E8. 
     The fusion protein may also comprise an amino acid sequence encoding, from an N-terminal side thereof,
         (D-1) an MHC molecule-restricted antigen peptide,   (D-2) a spacer sequence which may be optionally present,   (D-3) a single chain MHC molecule,   (D-4) a spacer sequence which may be optionally present, and   (D-5) a fusion peptide comprising a tetraspanin or a transmembrane domain thereof or MFG-E8 or a transmembrane domain thereof, and the at least one T-cell stimulatory cytokine, in this order.       

     The fusion protein may also contain an amino acid sequence encoding, from an N-terminal side thereof,
         (D-1) a fusion peptide comprising a tetraspanin or a transmembrane domain thereof or MFG-E8 or a transmembrane domain thereof, and the at least one T-cell stimulatory cytokine,   (D-2) a spacer sequence which may be optionally present,   (D-3) a single chain MHC molecule,   (D-4) a spacer sequence which may be optionally present, and   (D-5) an MHC molecule-restricted antigen peptide, in this order.       

     Here, the fusion peptide may also comprise an amino acid sequence encoding, from an N-terminal side thereof, 
     (1) a partial sequence of a tetraspanin containing a transmembrane domain 1, a small intracellular loop, a transmembrane domain 2, a small extracellular loop, and a transmembrane domain 3, 
     (2) a spacer sequence which may be present, 
     (3) the at least one T-cell stimulatory cytokine, 
     (4) a spacer sequence which may be present, and 
     (5) a partial sequence of a tetraspanin containing a transmembrane domain 4, in this order. 
     The fusion peptide may also comprise an amino acid sequence encoding, from an N-terminal side thereof, 
     (1) the at least one of T-cell stimulatory cytokine,
         (2) a spacer sequence which may be present, and   (3) MFG-E8, in this order.       

     In an embodiment of the present invention, the MHC molecule-restricted antigen peptide is an MHC class I molecule-restricted antigen peptide, the single chain MHC molecule may contain an extracellular domain of an MHC class Iα chain, the MHC molecule-restricted antigen peptide is an MHC class II molecule-restricted antigen peptide, and the single chain MHC molecule may contain an extracellular domain of an MHC class IIα chain and/or an extracellular domain of an MHC class IIβ chain. 
     In the aspect containing the fusion protein (D) having the functions of the constitutional requirement (A) and the constitutional requirement (B): 
     (C) a protein which contains at least one T-cell costimulatory molecule and is capable of allowing the T-cell costimulatory molecule to interact with T cells may be further contained in the membrane; 
     the protein capable of interacting with T cells may also contain the at least one T-cell costimulatory molecule, and a membrane protein capable of being expressed in membrane of an extracellular vesicle or a transmembrane domain thereof or a protein capable of binding to membrane of an extracellular vesicle or a domain thereof; and 
     the protein capable of interacting with T cells may also contain the at least one T-cell costimulatory molecule, and a tetraspanin or a transmembrane domain thereof or MFG-E8 or a domain thereof. 
     Vector and Kit 
     In an embodiment of the present invention, there is provided a vector comprising at least one polynucleotide selected from the polynucleotides described in the present specification. 
     The “vector” used in the present specification means any vector (examples thereof include, but are not limited to, a plasmid vector, a cosmid vectors a phage vector such as a phage, a viral vector such as an adenovirus vector or a baculovirus vector, and an artificial chromosome vector). The vector includes an expression vector, a cloning vector, and the like. The expression vector may generally contain a desired coding sequence and an appropriate polynucleotide required for expression of an operably linked coding sequence in a host organism (for example, a plant, an insect, an animal, or the like) or in an in vitro expression system. The cloning vector may be used to manipulate and/or amplify a desired polynucleotide fragment. The cloning vector may delete functional sequences required for expression of a desired polynucleotide fragment. 
     In an embodiment of the invention, all the polynucleotides described in the present specification may be inserted into the same vector, or two or more polynucleotides may be inserted into different vectors, as long as they can be operably inserted. In an embodiment of the present invention, there is provided a kit containing a combination of two or more vectors containing at least one polynucleotide selected from the polynucleotides described in the present specification. 
     Transformed Cells 
     In an embodiment of the present invention, there is provided a cell transformed with a vector comprising, 
     (i) a polynucleotide encoding the fusion protein or the protein complex of (A) described in the present specification, 
     (ii) a polynucleotide encoding the fusion protein of (B) described in the present specification, and 
     (iii) a polynucleotide encoding the fusion protein of (C) described in the present specification. 
     In an embodiment of the present invention, there is provided a cell transformed with a single vector or a combination of two or more vectors, the vector comprising, 
     (i) a polynucleotide encoding the fusion protein or the protein complex of (A) described in the present specification, 
     (ii) a polynucleotide encoding the fusion protein of (B) described in the present specification, and optionally, 
     (iii) a polynucleotide encoding the fusion protein of (C) described in the present specification. 
     In the cell of an embodiment of the present invention, as for the (A), (B), and (C) above, the cell may be transformed with a vector comprising a polynucleotide encoding fusion proteins to be one molecule obtained by fusing (A) and (B), a vector comprising a polynucleotide encoding fusion proteins to be one molecule obtained by fusing (B) and (C), or a vector comprising a polynucleotide encoding fusion proteins to be one molecule obtained by fusing (A), (B), and (C). Such a polynucleotide may encode one fusion protein with or without a spacer sequence between (A), (B), and (C). 
     Alternatively, the polynucleotide may encode a fusion protein obtained by functionally fusing the (A), (B), and (C) above by sharing an element for localizing the proteins thereof in the extracellular vesicle, that is, a site of a “membrane protein capable of being expressed in membrane of an extracellular vesicle or a transmembrane domain thereof” or a “protein capable of binding to membrane of an extracellular vesicle or a domain thereof”. 
     For example, in an embodiment of the present invention, 
     the cell may be transformed with a vector comprising a polynucleotide encoding a fusion protein (D) comprising: 
     (1) an antigen-presenting MHC molecule; 
     (2) at least one T-cell stimulatory cytokine; and 
     (3) a “membrane protein capable of being expressed in membrane of an extracellular vesicle or a transmembrane domain thereof” or a “protein capable of binding to membrane of an extracellular vesicle or a domain thereof”, 
     the fusion protein being fused in a form of sharing the site of the “membrane protein capable of being expressed in membrane of an extracellular vesicle or the transmembrane domain thereof” or the “protein capable of binding to membrane of an extracellular vesicle or the domain thereof” in (A) and (B); 
     a vector comprising a polynucleotide encoding a fusion protein (F) comprising: 
     (1) an antigen-presenting MHC molecule; 
     (2) a T-cell costimulatory molecule; and 
     (3) a “membrane protein capable of being expressed in membrane of an extracellular vesicle or a transmembrane domain thereof” or a “protein capable of binding to membrane of an extracellular vesicle or a domain thereof”, 
     the fusion protein being fused in a form of sharing the site of the “membrane protein capable of being expressed in membrane of an extracellular vesicle or the transmembrane domain thereof” or the “protein capable of binding to membrane of an extracellular vesicle or the domain thereof” in (A) and (C); 
     a vector comprising a polynucleotide encoding a fusion protein (G) comprising: 
     (1) at least one T-cell stimulatory cytokine; 
     (2) a T-cell costimulatory molecule; and 
     (3) a “membrane protein capable of being expressed in membrane of an extracellular vesicle or a transmembrane domain thereof” or a “protein capable of binding to membrane of an extracellular vesicle or a domain thereof”, 
     the fusion protein being fused in a form of sharing the site of the “membrane protein capable of being expressed in membrane of an extracellular vesicle or the transmembrane domain thereof” or the “protein capable of binding to membrane of an extracellular vesicle or the domain thereof” in (B) and (C); 
     or, 
     a vector comprising a polynucleotide encoding a fusion protein (E) comprising: 
     (1) an antigen-presenting MHC molecule; 
     (2) at least one T-cell stimulatory cytokine; 
     (3) a T-cell costimulatory molecule; and 
     (4) a “membrane protein capable of being expressed in membrane of an extracellular vesicle or a transmembrane domain thereof” or a “protein capable of binding to membrane of an extracellular vesicle or a domain thereof”, 
     the fusion protein being fused in a form of sharing the site of the “membrane protein capable of being expressed in membrane of an extracellular vesicle or the transmembrane domain thereof” or the “protein capable of binding to membrane of an extracellular vesicle or the domain thereof” in (A) to (C). 
     Alternatively, in an embodiment of the present invention, 
     there is provided a cell transformed with a vector comprising, 
     (iv) a polynucleotide encoding the fusion protein of (D) described in the present specification, in which the fusion protein contains an antigen-presenting MHC molecule and at least one T-cell stimulatory cytokine and is capable of presenting the antigen and the T-cell stimulatory cytokine outside membrane, the fusion protein being the fusion protein having the functions of the constitutional requirement (A) and the constitutional requirement (B) using the protein of the constitutional requirement (B) which contains a first T-cell stimulatory cytokine and is capable of presenting the first T-cell stimulatory cytokine outside membrane, instead of the membrane protein capable of being expressed in membrane of an extracellular vesicle or the transmembrane domain thereof or the protein capable of binding to membrane of an extracellular vesicle of the constitutional requirement (A). 
     The expression “transformed with a single vector or a combination of two or more vectors” means that, for example, the cell may be transformed with a single vector in which all the polynucleotides (i) to (iv) are inserted into the same vector, or may be transformed with a combination of two or more vectors in which two or more of the polynucleotides (i) to (iv) are inserted into different vectors. 
     In a case where (A) is a fusion protein, examples of “a single vector or a combination of two or more vectors” include the followings:
         a vector comprising a polynucleotide encoding the fusion protein of (A) and a polynucleotide encoding the fusion protein of (B);   a combination of a vector comprising a polynucleotide encoding the fusion protein of (A) and a vector comprising a polynucleotide encoding the fusion protein of (B);   a vector comprising a polynucleotide encoding the fusion protein of (A), a polynucleotide encoding the fusion protein of (B), and a polynucleotide encoding the fusion protein of (C);   a combination of a vector comprising a polynucleotide encoding the fusion protein of (A) and a polynucleotide encoding the fusion protein of (B), and a vector comprising a polynucleotide encoding the fusion protein of (C);   a combination of a vector comprising a polynucleotide encoding the fusion protein of (A) and a polynucleotide encoding the fusion protein of (C), and a vector comprising a polynucleotide encoding the fusion protein of (B);   a combination of a vector comprising a polynucleotide encoding the fusion protein of (B) and a polynucleotide encoding the fusion protein of (C), and a vector comprising a polynucleotide encoding the fusion protein of (A); and   a combination of a vector comprising a polynucleotide encoding the fusion protein of (A), a vector comprising a polynucleotide encoding the fusion protein of (B), and a vector comprising a polynucleotide encoding the fusion protein of (C).       

     Alternatively, in a case where (A) is a protein complex, examples of “a single vector or a combination of two or more vectors” include the followings:
         a vector comprising a polynucleotide encoding a fusion protein comprising an amino acid sequence consisting of (A-1) to (A-5), a polynucleotide encoding a protein comprising (A-6), and a polynucleotide encoding the fusion protein of (B);   a combination of a vector comprising a polynucleotide encoding a fusion protein comprising an amino acid sequence consisting of (A-1) to (A-5) and a polynucleotide encoding a protein comprising (A-6), and a vector comprising a polynucleotide encoding the fusion protein of (B);   a combination of a vector comprising a polynucleotide encoding a fusion protein comprising an amino acid sequence consisting of (A-1) to (A-5) and a polynucleotide encoding the fusion protein of (B), and a vector comprising a polynucleotide encoding a protein comprising (A-6);   a combination of a vector comprising a polynucleotide encoding a fusion protein comprising an amino acid sequence consisting of (A-1) to (A-5) and a vector comprising a polynucleotide encoding a protein comprising (A-6) and a polynucleotide encoding the fusion protein of (B);   a combination of a vector comprising a polynucleotide encoding a fusion protein comprising an amino acid sequence consisting of (A-1) to (A-5), a vector comprising a polynucleotide encoding a protein comprising (A-6), and a vector comprising a polynucleotide encoding the fusion protein of (B);   a vector comprising a polynucleotide encoding a fusion protein comprising an amino acid sequence consisting of (A-1) to (A-5), a polynucleotide encoding a protein comprising (A-6), a polynucleotide encoding the fusion protein of (B), and a polynucleotide encoding the fusion protein of (C);   a combination of a vector comprising a polynucleotide encoding a fusion protein comprising an amino acid sequence consisting of (A-1) to (A-5), a polynucleotide encoding a protein comprising (A-6), and a polynucleotide encoding the fusion protein of (B), and a vector comprising a polynucleotide encoding the fusion protein of (C);   a combination of a vector comprising a polynucleotide encoding a fusion protein comprising an amino acid sequence consisting of (A-1) to (A-5), a polynucleotide encoding the fusion protein of (B), and a polynucleotide encoding the fusion protein of (C), and a vector comprising a polynucleotide encoding a protein comprising (A-6);   a combination of a vector comprising a polynucleotide encoding a protein comprising (A-6), a polynucleotide encoding the fusion protein of (B), and a polynucleotide encoding the fusion protein of (C), and a vector comprising a polynucleotide encoding a fusion protein comprising an amino acid sequence consisting of (A-1) to (A-5);   a combination of a vector comprising a polynucleotide encoding a fusion protein comprising an amino acid sequence consisting of (A-1) to (A-5), a polynucleotide encoding a protein comprising (A-6), and a polynucleotide encoding the fusion protein of (C), and a vector comprising a polynucleotide encoding the fusion protein of (B);   a combination of a vector comprising a polynucleotide encoding a fusion protein comprising an amino acid sequence consisting of (A-1) to (A-5) and a polynucleotide encoding a protein comprising (A-6), and a vector comprising a polynucleotide encoding the fusion protein of (B) and a polynucleotide encoding the fusion protein of (C);   a combination of a vector comprising a polynucleotide encoding a fusion protein comprising an amino acid sequence consisting of (A-1) to (A-5) and a polynucleotide encoding the fusion protein of (B), and a vector comprising a polynucleotide encoding a protein comprising (A-6) and a polynucleotide encoding the fusion protein of (C);   a combination of a vector comprising a polynucleotide encoding a fusion protein comprising an amino acid sequence consisting of (A-1) to (A-5) and a polynucleotide encoding the fusion protein of (C), and a vector comprising a polynucleotide encoding a protein comprising (A-6) and a polynucleotide encoding the fusion protein of (B);   a combination of a vector comprising a polynucleotide encoding a fusion protein comprising an amino acid sequence consisting of (A-1) to (A-5), a vector comprising a polynucleotide encoding a protein comprising (A-6), and a vector comprising a polynucleotide encoding the fusion protein of (B) and a polynucleotide encoding the fusion protein of (C);   a combination of a vector comprising a polynucleotide encoding a fusion protein comprising an amino acid sequence consisting of (A-1) to (A-5), a vector comprising a polynucleotide encoding the fusion protein of (B), and a vector comprising a polynucleotide encoding a protein comprising (A-6) and a polynucleotide encoding the fusion protein of (C);   a combination of a vector comprising a polynucleotide encoding a fusion protein comprising an amino acid sequence consisting of (A-1) to (A-5), a vector comprising a polynucleotide encoding the fusion protein of (C), and a vector comprising a polynucleotide encoding a protein comprising (A-6) and a polynucleotide encoding the fusion protein of (B);   a combination of a vector comprising a polynucleotide encoding a protein comprising (A-6), a vector comprising a polynucleotide encoding the fusion protein of (B), and a vector comprising a polynucleotide encoding a fusion protein comprising an amino acid sequence consisting of (A-1) to (A-5) and a polynucleotide encoding the fusion protein of (C);   a combination of a vector comprising a polynucleotide encoding a protein comprising (A-6), a vector comprising a polynucleotide encoding the fusion protein of (C), and a vector comprising a polynucleotide encoding a fusion protein comprising an amino acid sequence consisting of (A-1) to (A-5) and a polynucleotide encoding the fusion protein of (B);   a combination of a vector comprising a polynucleotide encoding the fusion protein of (B), a vector comprising a polynucleotide encoding the fusion protein of (C), and a vector comprising a polynucleotide encoding a fusion protein comprising an amino acid sequence consisting of (A-1) to (A-5) and a polynucleotide encoding a protein comprising (A-6); and   a combination of a vector comprising a polynucleotide encoding a fusion protein comprising an amino acid sequence consisting of (A-1) to (A-5), a vector comprising a polynucleotide encoding a protein comprising (A-6), a vector comprising a polynucleotide encoding the fusion protein of (B), and a vector comprising a polynucleotide encoding the fusion protein of (C).       

     The cell to be transformed is not particularly limited as long as the antigen-presenting extracellular vesicle described in the present specification can be obtained after the transformation, and may be a primary cultured cell or an established cell, which may be a normal cell or a lesion cell containing cancerous or tumorigenic cells. In addition, the origin of the cell to be transformed is not particularly limited, and examples thereof include cells derived from animals such as mammals, for example, rodents such as a mouse, a rat, a hamster, and a guinea pig; lagomorph such as a rabbit; ungulates such as a pig, a cow, a goat, a horse, and a sheep; carnivora such as a dog and a cat; and primates such as a human, a monkey, a rhesus monkey, a crab-eating macaque, a marmoset, an orangutan, and a chimpanzee, plant-derived cells, and insect-derived cells. The cell to be transformed is preferably an animal-derived cell. Examples of the animal-derived cells include, but are not limited to, human embryonic kidney cells (including HEK293T cells and the like), human FL cells, Chinese hamster ovary cells (CHO cells), COS-7, Vero, mouse L cells, and rat GH3. 
     A method for transforming the cell is not particularly limited as long as it is a method capable of introducing a target polynucleotide into a cell. For example, the method for transforming the cell may be an electroporation method, a microinjection method, a calcium phosphate method, a cationic lipid method, a method using a liposome, a method using a non-liposomal material such as polyethyleneimine, a viral infection method, or the like. 
     The transformed cell may be a transformed cell transiently expressing the fusion protein or protein complex of (A), (B), (C), (D), (E), (F), and/or (G), or a transformed cell (stable cell strain) stably expressing the fusion protein or protein complex of (A), (B), (C), (D), (E), (F), and/or (G). 
     The culture conditions of the cell to be transformed are not particularly limited. For example, when the transformed cell is an animal-derived cell, for example, a medium generally used for cell culture or the like (for example, an RPMI1640 medium, an Eagle&#39;s MEM medium, a Dulbecco&#39;s modified Eagle medium (DMEM medium), a Ham F12 medium, or any combination thereof), a medium obtained by adding other components such as fetal bovine serum, antibiotics, and amino acids, or the like may be used, and the cell may be cultured (for example, under being left or shaking), for example, in the presence of about 1 to about 10% (preferably about 2 to about 5%) of CO 2  at about 30 to about 40° C. (preferably about 37° C.) for a predetermined time (for example, about 0.5 hours to about 240 hours (preferably about 5 to about 120 hours, and more preferably about 12 to about 72 hours)). 
     A culture supernatant obtained by culturing the transformed cell may comprise the antigen-presenting extracellular vesicles described in the present specification. Therefore, when the transformed cell is cultured to obtain the antigen-presenting extracellular vesicles described in the present specification, a medium (for example, a Dulbecco&#39;s modified Eagle medium or the like containing about 1 to about 5% fetal bovine serum from which exosomes are removed) from which extracellular vesicles such as exosomes are removed may be used, if necessary. 
     Culture Supernatant 
     In an embodiment of the present invention, a culture supernatant obtained by culturing the transformed cell described in the present specification is provided. 
     The antigen-presenting extracellular vesicles contained in the culture supernatant described in the present specification can be further collected, for example, by purifying (for example, centrifugation, chromatography, and the like), concentrating, and isolating the culture supernatant. 
     In an embodiment of the present invention, antigen-presenting extracellular vesicles obtained from the culture supernatant described in the present specification are provided. 
     Method for Preparing Antigen-Presenting Extracellular Vesicles Described in Present Specification 
     The antigen-presenting extracellular vesicles described in the present specification may be obtained by, for example, means such as genetic recombination techniques known to those skilled in the art (for example, by the method described below or by the method described in Examples), but the present invention is not limited to. 
     A polynucleotide encoding the proteins of (A) and (B) described above (or (D) instead of (A) and (B)), and if necessary, (C), respectively, is obtained by normal genetic recombination techniques, and can be operably inserted into the same or different vectors. In a case where two or more polynucleotides encoding the proteins of (A) and (B) (or (D) instead of (A) and (B)), and if necessary, (C), respectively, are inserted into the same vector, each of the polynucleotides may be operably linked to the same or different promoters. The obtained single or two or more vectors can be transformed into cells simultaneously or sequentially to obtain transformed cells (may be transformed cells that transiently express these fusion proteins, or may be transformed cells (stable strains) that stably express these fusion proteins). The obtained transformed cells are cultured under desired conditions to obtain a culture supernatant, and the obtained culture supernatant is purified (for example, purification using centrifugation, antibodies (for example, antibodies recognizing a protein or the like contained in membrane of an extracellular vesicle), chromatography, flow cytometry, or the like), concentrated (for example, ultrafiltration or the like), and dried, such that the antigen-presenting extracellular vesicles described in the present specification can be obtained. 
     Alternatively, in a case where soluble proteins are used as the proteins of (A) and (B) (or (D) instead of (A) and (B)) described above, and if necessary, (C), for example, the antigen-presenting extracellular vesicles described in the present specification may be obtained by the following method. 
     As soluble proteins, the (A) and (B) (or (D) instead of (A) and (B)) described above, and if necessary, (C) obtained by normal genetic recombination techniques are used, or commercially available products thereof may be used. Next, extracellular vesicles are obtained from desired cells, for example, by a known method, the method described in the present specification, or a method similar thereto. Next, the obtained extracellular vesicles and one or more the soluble proteins described above are reacted in a desired solvent under desired conditions (for example, the method described in JP 2018-104341 A and the like may be referred to). The antigen-presenting extracellular vesicles described in the present specification can be obtained by carrying out this operation under appropriately changed conditions until the soluble proteins of (A) and (B) (or (D) instead of (A) and (B)), and if necessary, (C), are contained in the membrane of the extracellular vesicle. 
     Alternatively, in a case where soluble proteins are used as the proteins of (A) and (B) (or (D) instead of (A) and (B)) described above, and if necessary, (C), for example, the antigen-presenting extracellular vesicles described in the present specification may be obtained by the following method. 
     As the soluble proteins of (A) and (B) (or (D) instead of (A) and (B)), and if necessary, (C), proteins containing a desired tag added to the N-terminus or C-terminus thereof (examples thereof include a His tag, a FLAG tag, and a PNE tag of SEQ ID NO: 79, and all the tags may be the same tag or different types of tags) are obtained by normal genetic recombination techniques. Next, extracellular vesicles are obtained from the desired cells, for example, by known methods, the methods described in the present specification, or methods similar thereto, and antibodies against these tags or antigen-binding fragments thereof (for example, scFv, Fab, or a nanobody, such as an anti-PNE tag nanobody of SEQ ID NO: 83) and the like are bound to the extracellular vesicles via a peptide linker or the like, if necessary; alternatively, polynucleotides (for example, SEQ ID NO: 88, 90, and the like) are obtained by normal genetic recombination techniques, the polynucleotides encoding a fusion protein (for example, a fusion protein of SEQ ID NO: 89 of an anti-PNE nanobody (SEQ ID NO: 83), CD8a (SEQ ID NO: 85), and CD81 (SEQ ID NO: 15)) to which an antibody or an antigen-binding fragment thereof (for example, scFv, Fab, or a nanobody) at the N-terminus or C-terminus of a membrane protein capable of being expressed in membrane of an extracellular vesicle or a transmembrane domain thereof, or the like is bonded, transformed cells (the fusion protein may be a transformed cell that is transiently expressed or a transformed cell (stable strain) that is stably expressed) are obtained by transforming cells using the polynucleotides operably inserted into a vector, the obtained transformed cell are cultured or the like, and extracellular vesicles are recovered by the method described above and the like. The antigen-presenting extracellular vesicles described in the present specification may be obtained by mixing the soluble proteins (A) and (B), and if necessary, (C) to which a tag is added, and extracellular vesicles containing, in membranes thereof, proteins containing antibodies against to the tag or antigen-binding fragments thereof (for example, scFv, Fab, and a nanobody) under predetermined conditions. 
     Alternatively, the antigen-presenting extracellular vesicles described in the specification may be obtained from the transformed cells obtained by performing transformation using a combination of polynucleotides encoding the fusion proteins of (A) to (G). 
     Alternatively, the antigen-presenting extracellular vesicles described in the present specification may be obtained by a combination of two or more of the methods described above. 
     The antigen-presenting extracellular vesicles described in the present specification may recognize that the proteins of (A) and (B) (or (D) instead of (A) and (B)), and if necessary, (C) are contained in the membrane by, for example, methods such as flow cytometry, ELISA, and Western blotting. 
     In an embodiment of the present invention, there is provided a method for preparing the antigen-presenting extracellular vesicles described in the present specification, the method comprising collecting a culture supernatant obtained by culturing the transformed cells described in the present specification. 
     In an embodiment of the present invention, there is provided a method for preparing the antigen-presenting extracellular vesicles described in the present specification, the method comprising: 
     simultaneously or sequentially (preferably simultaneously) transforming cells with a single vector or a combination of two or more vectors, the vector comprising, 
     (i) a polynucleotide encoding the fusion protein or the protein complex of (A) described in the present specification, 
     (ii) a polynucleotide encoding the fusion protein of (B) described in the present specification, and optionally, 
     (iii) a polynucleotide encoding the fusion protein of (C) described in the present specification; and 
     collecting a culture supernatant obtained by culturing the obtained transformed cells. 
     Alternatively, in an embodiment of the present invention, there is provided a method for preparing the antigen-presenting extracellular vesicles described in the present specification, the method comprising: 
     simultaneously or sequentially (preferably simultaneously) transforming cells with a single vector or a combination of two or more vectors, the vector comprising, 
     (iv) a polynucleotide encoding the fusion protein of (D) described in the present specification, in which the fusion protein comprises an antigen-presenting MHC molecule and at least one T-cell stimulatory cytokine and is capable of the antigen and the T-cell stimulatory cytokine outside membrane, and optionally, 
     (iii) a polynucleotide encoding the fusion protein of (C) described in the present specification; and 
     collecting a culture supernatant obtained by culturing the obtained transformed cells. 
     Alternatively, in an embodiment of the present invention, there is provided a method for preparing the antigen-presenting extracellular vesicles described in the present specification, the method comprising: 
     transforming cells with a vector comprising, 
     (v) a polynucleotide encoding the fusion protein of (E) described in the present specification, in which the fusion protein contains an antigen-presenting MHC molecule, at least one T-cell stimulatory cytokine, and a T-cell costimulatory molecule, and is capable of the antigen and the T-cell stimulatory cytokine outside membrane; and 
     collecting a culture supernatant obtained by culturing the obtained transformed cells. 
     In an embodiment of the present invention, antigen-presenting extracellular vesicles obtained from the culture supernatant described in the present specification are provided. 
     In an embodiment of the present invention, there is provided an antigen-presenting extracellular vesicle obtained by a method comprising: 
     simultaneously or sequentially (preferably simultaneously) transforming cells with a single vector or a combination of two or more vectors, the vector comprising, 
     (i) a polynucleotide encoding the fusion protein or the protein complex of (A) described in the present specification, 
     (ii) a polynucleotide encoding the fusion protein of (B) described in the present specification, and optionally, 
     (iii) a polynucleotide encoding the fusion protein of (C) described in the present specification; and collecting a culture supernatant obtained by culturing the obtained transformed cells. 
     Alternatively, in an embodiment of the present invention, there is provided an antigen-presenting extracellular vesicle obtained by a method comprising: 
     simultaneously or sequentially (preferably simultaneously) transforming cells with a single vector or a combination of two or more vectors, the vector comprising, 
     (iv) a polynucleotide encoding the fusion protein of (D) described in the present specification, in which the fusion protein comprises an antigen-presenting MHC molecule and at least one T-cell stimulatory cytokine and is capable of the antigen and the T-cell stimulatory cytokine outside membrane, and optionally, 
     (iii) a polynucleotide encoding the fusion protein of (C) described in the present specification; and 
     collecting a culture supernatant obtained by culturing the obtained transformed cells. 
     Alternatively, in an embodiment of the present invention, there is provided an antigen-presenting extracellular vesicle obtained by a method comprising: 
     transforming cells with, 
     (v) a polynucleotide encoding the fusion protein of (E) described in the present specification, in which the fusion protein comprises an antigen-presenting MHC molecule, at least one T-cell stimulatory cytokine, and a T-cell costimulatory molecule, and is capable of the antigen and the T-cell stimulatory cytokine outside membrane; and 
     collecting a culture supernatant obtained by culturing the obtained transformed cells. 
     Composition and Use 
     In an embodiment of the present invention, there is provided a composition (for example, a pharmaceutical composition) containing the antigen-presenting extracellular vesicle described in the present specification, a polynucleotide and/or a vector comprising the same, and/or a transformed cell and/or a culture supernatant thereof. In an embodiment of the present invention, there is provided a pharmaceutical composition containing the antigen-presenting extracellular vesicle described in the present specification or the culture supernatant described in the present specification. 
     Examples of the composition (for example, the pharmaceutical composition) described in the present specification comprise, but are not limited to, additives such as an excipient, a lubricant, a binder, a disintegrant, a pH regulator, a solvent, a solubilizing aid, a suspending agent, an isotonicifier, a buffer, an analgesic, a preservative, an antioxidant, a colorant, a sweetener, and a surfactant. Those skilled in the art can appropriately select the types of these additives, the amount of these additives used, and the like depending on the purpose. In a case where the pharmaceutical composition is used, these additives are preferably pharmacologically acceptable carriers. Furthermore, in a case where the composition described in the present specification contains a polynucleotide, it is preferable to contain carriers suitable for a drug delivery (DD) of nucleic acids, although not required, and examples of these carriers include lipid nanoparticles (LNP) and polymers (for example, PEI). 
     The composition (for example, the pharmaceutical composition) described in the present specification can be formulated into, for example, a tablet, a coated tablet, an orally disintegrating tablet, a chewable agent, a pill, granules, fine granules, a powder, a hard capsule, a soft capsule, a solution (examples thereof include a syrup, an injection, and a lotion), a suspension, an emulsion, a jelly, a patch, an ointment, a cream, an inhalant, a suppository, and the like by a method known per se together with the additives described above. The composition may be an oral agent or a parenteral agent. The formulated composition may further contain other beneficial components (for example, other therapeutically beneficial components) depending on the purpose thereof. 
     The composition according to an embodiment of the present invention can enhance acquired immunity (cellular immunity and/or humoral immunity) to a specific antigen as shown in test examples, and can be used as a pharmaceutical composition for treating or preventing an infectious disease caused by an infectious pathogen when a peptide derived from an infectious pathogen (pathogenic bacteria, viruses, or the like) is used as an antigen. 
     In addition, as shown in the test examples, the composition according to an embodiment of the present invention can eliminate infectious pathogens by allowing induction of inflammatory cytokines and activating innate immunity (including mobilizing and activating neutrophils, monocytes, macrophages, and the like to phagocytize pathogenic bacteria), and can be used as a pharmaceutical composition for treating or preventing an infectious disease caused by infectious pathogens. 
     The antigen-presenting extracellular vesicle (preferably the antigen-presenting extracellular vesicle containing an MHC class I-restricted antigen peptide and an MHC class I molecule in the membrane), the polynucleotide and/or the vector comprising the same, and/or the transformed cell and/or the culture supernatant thereof described in the present specification, or the composition comprising them (for example, the pharmaceutical composition) may be useful for treating or preventing cancer. 
     Therefore, in an embodiment of the present invention, there are provided, for treating or preventing cancer, the antigen-presenting extracellular vesicle, the polynucleotide and/or the vector comprising the polynucleotide, and/or the transformed cell and/or the culture supernatant thereof described in the present specification, or the composition (for example, a pharmaceutical composition) comprising them. As shown in the test examples, the antigen-presenting extracellular vesicles and the like according to an embodiment of the present invention can proliferate and activate antigen-specific cytotoxic T cells to be used, and when a tumor-associated antigen peptide is used as an antigen to be used, the proliferated and activated cytotoxic T cells recognize and attack cancer cells, such that the cancer cells can be killed. 
     In another embodiment of the present invention, there is provided a use of the antigen-presenting extracellular vesicle, the polynucleotide and/or the vector comprising the polynucleotide, and/or the transformed cell and/or the culture supernatant thereof described in the present specification, or the composition (for example, a pharmaceutical composition) comprising them, in the manufacture of a medicament for treating or preventing cancer. 
     In still another embodiment of the present invention, there is provided a method for treating or preventing cancer, the method including administering an effective amount of the antigen-presenting extracellular vesicle, the polynucleotide and/or the vector comprising the polynucleotide, and/or the transformed cell and/or the culture supernatant thereof described in the present specification, or the composition comprising them to a subject in need thereof. 
     The cancer includes any solid cancer or blood cancer, and examples thereof include, but are not limited to, small cell lung cancer, non-small cell lung cancer, breast cancer, esophageal cancer, stomach cancer, small intestine cancer, large intestine cancer, colon cancer, rectal cancer, pancreatic cancer, prostate cancer, bone marrow cancer, kidney cancer (including kidney cell cancer), parathyroid cancer, adrenal cancer, ureteral cancer, liver cancer, bile duct cancer, cervical cancer, ovarian cancer (for example, the tissue type thereof is serous gland cancer, mucous gland cancer, clear cell adenocarcinoma cancer, and the like), testicular cancer, bladder cancer, external pudendal cancer, penis cancer, thyroid cancer, head and neck cancer, craniopharyngeal cancer, pharyngeal cancer, tongue cancer, skin cancer, Merkel cell cancer, melanoma (malignant melanoma and the like), epithelial cancer, squamous cell carcinoma, basal cell cancer, childhood cancer, unknown primary cancer, fibrosarcoma, mucosal sarcoma, liposarcoma, chondrosarcoma, osteogenic sarcoma, spinal cord tumor, angiosarcoma, lymphangiosarcoma, lymphangiosarcoma, Kaposi&#39;s sarcoma, leiomyosarcoma, rhabdomyosarcoma, synovial tumor, mesothelioma, ewing tumor, seminoma, Wilms tumor, brain tumor, glioma, glioblastoma, astrocytoma, myeloblastoma, meningioma, neuroblastoma, medulloblastoma, retinoblastoma, spinal tumor, malignant lymphoma (for example, non-Hodgkin&#39;s lymphoma, Hodgkin&#39;s lymphoma, and the like), chronic or acute lymphocytic leukemia, and adult T-cell leukemia. 
     In an embodiment of the present invention, immune checkpoint inhibitors can be used in combination to treat or prevent cancer. The immune checkpoint inhibitors may be administered simultaneously or sequentially to a patient, or may be contained in the pharmaceutical according to the present invention. 
     Examples of the immune checkpoint inhibitor include, but are not limited to, a PD-1 inhibitor (for example, an anti-PD-1 antibody such as nivolumab or pembrolizumab), a CTLA-4 inhibitor (for example, an anti-CTLA-4 antibody such as ipilimumab), and a PD-L1 inhibitor (for example, an anti-PD-L1 antibody such as durvalumab, atezolizumab, or avelumab). In a case where the immune checkpoint inhibitor is an antibody or an active fragment thereof, the antibody or the active fragment thereof may be bound to a membrane protein capable of being localized onto membrane of an extracellular vesicle or a transmembrane domain thereof or a protein capable of binding to membrane of an extracellular vesicle or a membrane-binding domain thereof to be present on the membrane of the extracellular vesicle according to the present invention. 
     A combination of these immune checkpoint inhibitors enhances cytotoxicity against cancer cells. 
     The antigen-presenting extracellular vesicle (preferably the antigen-presenting extracellular vesicle containing an MHC class II-restricted antigen peptide and an MHC class II molecule in the membrane), the polynucleotide and/or the vector comprising the same, and/or the transformed cell and/or the culture supernatant thereof described in the present specification, or the composition comprising them may be useful for treating or preventing an autoimmune disease. As exemplified in the test examples, the antigen-presenting extracellular vesicles according to an embodiment of the present invention can proliferate and activate antigen-specific regulatory T cells (Treg) to be used, and when an auto-antigen peptide is used as an antigen to be used, the proliferated and activated Treg induces tolerance to the auto-antigen, such that the autoimmune disease can be treated or prevented. 
     Therefore, in an embodiment of the present invention, there are provided, for treating or preventing an autoimmune disease, the antigen-presenting extracellular vesicle, the polynucleotide and/or the vector comprising the polynucleotide, and/or the transformed cell and/or the culture supernatant thereof described in the present specification, or the composition (for example, a pharmaceutical composition) comprising them. 
     In another embodiment of the present invention, there is provided a use of the antigen-presenting extracellular vesicle, the polynucleotide and/or the vector comprising the polynucleotide, and/or the transformed cell and/or the culture supernatant thereof described in the present specification, or the composition (for example, a pharmaceutical composition) containing them, for producing a pharmaceutical for treating or preventing an autoimmune disease. 
     In still another embodiment of the present invention, there is provided a method for treating or preventing an autoimmune disease, the method including administering an effective amount of the antigen-presenting extracellular vesicle, the polynucleotide and/or the vector comprising the polynucleotide, and/or the transformed cell and/or the culture supernatant thereof described in the present specification, or the composition containing them to a subject who requires them. 
     Examples of the autoimmune disease include, but are not limited to, asthma, psoriasis, systemic erythematosus, Guillain-Barre syndrome, Sjogren&#39;s syndrome, multiple sclerosis, myasthenia gravis, malignant anemia, Basedow&#39;s disease, Hashimoto thyroiditis, type I diabetes, Crohn&#39;s disease, inflammatory bowel disease, and rheumatoid arthritis. 
     The antigen-presenting extracellular vesicle (preferably the antigen-presenting extracellular vesicle containing an MHC class II-restricted antigen peptide and an MHC class II molecule in the membrane), the polynucleotide and/or the vector comprising the same, and/or the transformed cell and/or the culture supernatant thereof described in the present specification, or the composition comprising them (for example, the pharmaceutical composition) may be useful for treating or preventing an allergic disease. As shown in the test examples, the antigen-presenting extracellular vesicles according to an embodiment of the present invention can proliferate and activate antigen-specific regulatory T cells (Treg) to be used, and when an allergen is used as an antigen to be used, the proliferated and activated Treg induces tolerance to the allergen, such that the allergic disease can be treated or prevented. 
     Therefore, in an embodiment of the present invention, there are provided, for treating or preventing an allergic disease, the antigen-presenting extracellular vesicle, the polynucleotide and/or the vector comprising the polynucleotide, and/or the transformed cell and/or the culture supernatant thereof described in the present specification, or the composition (for example, a pharmaceutical composition) containing them. 
     In another embodiment of the present invention, there is provided a use of the antigen-presenting extracellular vesicle, the polynucleotide and/or the vector comprising the polynucleotide, and/or the transformed cell and/or the culture supernatant thereof described in the present specification, or the composition (for example, a pharmaceutical composition) comprising them, for producing a pharmaceutical for treating or preventing an allergic disease. 
     In still another embodiment of the present invention, there is provided a method for treating or preventing an allergic disease, the method including administering an effective amount of the antigen-presenting extracellular vesicle, the polynucleotide and/or the vector comprising the polynucleotide, and/or the transformed cell and/or the culture supernatant thereof described in the present specification, or the composition containing them to a subject who requires them. 
     Examples of the allergic disease include, but are not limited to, allergic rhinitis, atopic dermatitis, allergic asthma, allergic conjunctivitis, allergic gastro-enteritis, food allergies, drug allergies, and urticaria. 
     Examples of the subject to be treated or prevented from the various diseases described above include, but are not limited to, animals such as mammals, for example, rodents such as a mouse, a rat, a hamster, and a guinea pig; lagomorph such as a rabbit; ungulates such as a pig, a cow, a goat, a horse, and a sheep; carnivora such as a dog and a cat; and primates such as a human, a monkey, a rhesus monkey, a crab-eating macaque, a marmoset, an orangutan, and a chimpanzee; and plants. The subject is preferably an animal, more preferably a rodent or a primate, and sill more preferably a mouse or a human. 
     A dosage of a formulation obtained by formulating the antigen-presenting extracellular vesicle, the polynucleotide and/or the vector comprising the polynucleotide, and/or the transformed cell and/or the culture supernatant thereof described in the present specification, or the composition containing them can be appropriately determined in consideration of a gender, an age, a weight, a health status, a degree of medical condition, or a diet of a subject to be administered, an administration time, an administration method, a combination with other drugs, and other factors. 
     Method for Activating, Proliferating, and/or Differentiating T cells against Specific Antigen 
     The antigen-presenting extracellular vesicles described in the present specification can activate, proliferate, and differentiate T cells against a specific antigen by contacting with the T cells (although not limited thereto, for example, T cells or T cell populations obtained from peripheral blood, spleen, and the like) in vitro, ex vivo, and/or in vivo. 
     In an embodiment of the present invention, there is provided a method for activating, proliferating, and/or differentiating T cells against a specific antigen, the method comprising bringing the antigen-presenting extracellular vesicles described in the present specification into contact with T cells in vitro or ex vivo. 
     In an embodiment of the present invention, there are provided T cells obtained by the method described above. 
     The T cells obtained by the method described above may be administered to a subject in order to treat and/or prevent a disease (for example, cancer, an autoimmune disease, an allergic disease, or the like). 
     EXAMPLES 
     Hereinafter, the present invention will be described in more detail with reference to examples, and these examples do not limit the scope of the present invention at all. 
     Preparation 1 of Plasmid 
     A vector for expressing, on membrane of an extracellular vesicle, an MHC class I molecule capable of presenting an antigen outside membrane was prepared using a pCAG-puro vector. 
     With established cloning techniques, a single chain trimer (sc-Trimer) consisting of a polynucleotide (SEQ ID NO: 2) encoding a signal peptide (amino acids 1 to 20; SEQ ID NO: 1) of β 2  microglobulin, a polynucleotide (SEQ ID NO: 4) encoding an OVA peptide (SEQ ID NO: 3) as a model antigen peptide, a peptide linker (amino acid sequence: SEQ ID NO: 5, polynucleotide: SEQ ID NO: 6), a polynucleotide (SEQ ID NO: 8) encoding a full-length sequence (amino acids 21 to 119; SEQ ID NO: 7) of β 2  microglobulin from which a signal peptide was removed, a polynucleotide (SEQ ID NO: 12) encoding a peptide linker (SEQ ID NO: 11), and a polynucleotide (SEQ ID NO: 10) encoding a full-length sequence (amino acids 22 to 369; SEQ ID NO: 9) of an MHC class Iα chain from which a signal peptide was removed was prepared (amino acid sequence: SEQ ID NO: 13; polynucleotide: SEQ ID NO: 14). Next, a polynucleotide (SEQ ID NO: 18; corresponding amino acid sequence: SEQ ID NO: 17) in which a sc-Trimer was linked to a polynucleotide (SEQ ID NO: 16) encoding a full-length sequence (amino acids 1 to 236; SEQ ID NO: 15) of CD81 as a tetraspanin was inserted into the pCAG-puro vector ( FIGS.  1 A and  1 B : hereinafter, sc-Trimer-CD81). 
     With the same method, in order to express CD80 as one of T-cell costimulatory molecules on membrane of an extracellular vesicle, a polynucleotide (SEQ ID NO: 24; corresponding amino acid sequence: SEQ ID NO: 23) in which a polynucleotide (SEQ ID NO: 20) encoding a full-length sequence (amino acids 1 to 306; SEQ ID NO: 19) of CD80 was linked to a polynucleotide (SEQ ID NO: 22) encoding a full-length sequence (amino acids 1 to 306; SEQ ID NO: 21) of CD9 as a tetraspanin was inserted into a pCAG-puro or pMX vector ( FIGS.  1 C and  1 D : hereinafter, CD80-CD9). 
     With the same method, in order to express IL-2 as one of T-cell stimulatory cytokines on membrane of an extracellular vesicle, a polynucleotide (SEQ ID NO: 26) encoding a full-length sequence (amino acids 21 to 169; SEQ ID NO: 25) from which a single peptide of IL-2 was removed was inserted between the amino acids 170C and 1711 in a large extracellular loop of a mouse CD63 (amino acids 1 to 238; SEQ ID NO: 27; polynucleotide: SEQ ID NO: 28) as a tetraspanin (that is, a sequence of IL-2 was inserted between a polynucleotide (SEQ ID NO: 58) encoding a partial sequence of CD63 of SEQ ID NO: 57 and a polynucleotide (SEQ ID NO: 60) encoding a partial sequence of CD63 of SEQ ID NO: 59). Note that polynucleotides (SEQ ID NO: 30) encoding a peptide linker (amino acid sequence GGGGS: SEQ ID NO: 29) were added to the N-terminus and the C-terminus of IL-2, respectively. The polynucleotide (SEQ ID NO: 32; corresponding amino acid sequence: SEQ ID NO: 31) was inserted into the pCAG-puro vector ( FIGS.  1 E and  1 F : hereinafter, CD63-IL-2). 
     Preparation 2 of Plasmid 
     A vector for expressing, on membrane of an extracellular vesicle, an MHC class II molecule capable of presenting an antigen outside membrane was prepared using a pCAG-puro vector. 
     With established cloning techniques, a single chain dimer (sc-Dimer) in which a polynucleotide (SEQ ID NO: 34) encoding a signal peptide (amino acids 1 to 27; SEQ ID NO: 33) of an MHC class III chain, a polynucleotide (SEQ ID NO: 36) encoding an OVA peptide (SEQ ID NO: 35) as a model antigen peptide, and a polynucleotide (SEQ ID NO: 38) encoding a full-length sequence (amino acids 28 to 265; SEQ ID NO: 37) of an MHC class IIβ chain from which a signal peptide was removed were linked by a polynucleotide (SEQ ID NO: 40) encoding a peptide linker (SEQ ID NO: 39) was prepared (amino acid sequence: SEQ ID NO: 41; polynucleotide: SEQ ID NO: 42). Next, a polynucleotide (SEQ ID NO: 44; corresponding amino acid sequence: SEQ ID NO: 43) in which a sc-Dimer was linked to a polynucleotide (SEQ ID NO: 16) encoding a full-length sequence (amino acids 1 to 236; SEQ ID NO: 15) of CD81 as a tetraspanin was inserted into the pCAG-puro vector ( FIGS.  1 G and  1 H : hereinafter, sc-Dimer-CD81). 
     A polynucleotide (SEQ ID NO: 46) encoding a full-length sequence (amino acids 1 to 256; SEQ ID NO: 45) of an MHC class IIα chain as a constituent element of an MHC class II molecule was inserted into another pCAG-puro vector ( FIG.  1 I : hereinafter, an MHC class IIα chain). 
     With the same method, in order to express TGF-β1 as one of T-cell stimulatory cytokines on membrane of an extracellular vesicle, a polynucleotide (SEQ ID NO: 48) encoding a full-length sequence (amino acids 1 to 390; SEQ ID NO: 47) of TGF-β1 in which three 33 rd , 223 rd , and 225 th  C&#39;s of a LAP domain were changed to S&#39;s and a polynucleotide (SEQ ID NO: 50) encoding a full-length sequence (amino acids 23 to 463; SEQ ID NO: 49) from which a signal peptide of MFG-E8 in which 89 th  D was changed to E was removed were linked by a polynucleotide (SEQ ID NO: 30) encoding a peptide linker (SEQ ID NO: 29). The polynucleotide (SEQ ID NO: 52; corresponding amino acid sequence: SEQ ID NO: 51) was inserted into the pCAG-puro vector ( FIGS.  1 J and  1 K : hereinafter, TGF-β-MFG-E8). 
     With the same method, in order to express IL-4 as one of T-cell stimulatory cytokines on membrane of an extracellular vesicle, a polynucleotide (SEQ ID NO: 54) encoding a full-length sequence (amino acids 21 to 140; SEQ ID NO: 53) from which a single peptide of IL-4 was removed was inserted between the amino acids 177S and 178G in a large extracellular loop of a mouse CD81 (amino acids 1 to 236; SEQ ID NO: 15; polynucleotide: SEQ ID NO: 16) as a tetraspanin (that is, a sequence of IL-4 was inserted between a polynucleotide (SEQ ID NO: 62) encoding a partial sequence of CD81 of SEQ ID NO: 61 and a polynucleotide (SEQ ID NO: 64) encoding a partial sequence of CD81 of SEQ ID NO: 63). Note that polynucleotides (SEQ ID NO: 30) encoding a peptide linker (amino acid sequence GGGGS; SEQ ID NO: 29) were added to the N-terminus and the C-terminus of IL-4, respectively. The polynucleotide (SEQ ID NO: 56; corresponding amino acid sequence: SEQ ID NO: 55) was inserted into the pCAG-puro vector ( FIGS.  1 L and  1 M : hereinafter, CD81-IL-4). 
     Preparation 3 of Plasmid 
     sc-Dimer-CD81-IL-12p40 
     At the sc-Dimer, a polynucleotide (SEQ ID NO: 92) encoding a protein (SEQ ID NO: 91) obtained by fusing CD81 to IL-12p40 as a subunit of IL-12 as a T-cell stimulatory cytokine was inserted into a pCAG-puro vector, thereby preparing a vector expressing a fusion protein. 
     IL-12p35 
     A polynucleotide (SEQ ID NO: 98) encoding IL-12p35 (SEQ ID NO: 97) as one subunit of IL-12 was inserted into a pCAG-puro or pMX vector to prepare a vector expressing IL-12p35. 
     CD81-IL-6 
     In order to express IL-6 as one of T-cell stimulatory cytokines on membrane of an extracellular vesicle, a polynucleotide (SEQ ID NO: 100) encoding a full-length sequence (SEQ ID NO: 99) from which a signal peptide of IL-6 was removed was introduced into a polynucleotide encoding an extracellular loop of CD81 as a tetraspanin, and a polynucleotide (SEQ ID NO: 102) encoding a CD81-IL-6 fusion protein (SEQ ID NO: 101) was inserted into a pCAG-puro or pMX vector, thereby preparing a vector expressing a fusion protein. 
     hCD80-hCD9 
     In order to express human CD80 as one of T-cell costimulatory molecules on membrane of an extracellular vesicle, a polynucleotide (SEQ ID NO: 108) encoding a fusion protein (SEQ ID NO: 107) of human CD80 and human CD9 as a tetraspanin was inserted into a pCAG-puro or pMX vector, thereby preparing a vector expressing a fusion protein. 
     sc-Trimer-CD81-IL-2 
     In order to express IL-2 as one of T-cell stimulatory cytokines on membrane of an extracellular vesicle, similar to the CD81-IL-4, a polynucleotide encoding a fusion peptide of CD81-IL2 was prepared, a sequence of the polynucleotide was linked to a nucleotide encoding a sc-Trimer-, and a polynucleotide (SEQ ID NO: 136) encoding sc-Trimer-CD81-IL-2 (SEQ ID NO: 135) was prepared and inserted into a pCAG-puro or pMX vector, thereby preparing a vector expressing a fusion protein. 
     hsc-Trimer-hCD81 
     Using the sc-Trimer-CD81 as a human gene sequence (using HLA-A2402 as a sequence of MHC-I), a polynucleotide (SEQ ID NO: 132) encoding hsc-Trimer-hCD81 (SEQ ID NO: 131) was prepared and inserted into a pCAG-puro or pMX vector to prepare a vector expressing a fusion protein. 
     SARS-CoV2sc-Trimer-hCD81 
     Using a SARS-CoV-2 peptide (amino acid sequence: SEQ ID NO: 141; polynucleotide: SEQ ID NO: 142) as an antigen and HLA-A0201 as an MHC molecule, a polynucleotide (SEQ ID NO: 148) encoding an antigen-presenting MHC molecule (SARS-CoV2sc-Trimer; amino acid sequence: SEQ ID NO: 147) was prepared and was further linked to a polynucleotide encoding hCD81, thereby preparing a polynucleotide (SEQ ID NO: 150) encoding SARS-CoV2sc-Trimer-hCD81 (SEQ ID NO: 149). The prepared polynucleotide was inserted into a pCAG-puro or pMX vector to prepare a vector expressing a fusion protein. 
     hCD63-hIL-2 
     The CD63-IL-2 was prepared using a human gene sequence. A polynucleotide (SEQ ID NO: 116) encoding hCD63-hIL-2 (SEQ ID NO: 115) was prepared and inserted into a pCAG-puro or pMX vector to prepare a vector expressing a fusion protein. 
     CD63-Akaluc 
     As a negative control, CD63 and Akaluc luciferase were fused to prepare a polynucleotide (SEQ ID NO: 140) for localizing an AlkaLuc fusion protein (SEQ ID NO: 139) to an extracellular vesicle, and the polynucleotide was inserted into a pCAG-puro or pMX vector, thereby preparing a vector expressing a fusion protein. 
     The respective sequences used in examples are shown in Tables 1 to 13. Note that the underline portion in each sequence indicates a signal peptide. 
     
       
         
           
               
               
               
             
               
                 TABLE 1 
               
               
                   
               
               
                   
                   
                 SEQ 
               
               
                   
                   
                 ID  
               
               
                   
                 Sequence 
                 NO: 
               
               
                   
               
             
            
               
                 Signal  
                 
                   MARSVTLVFLVLVSLTGLYA 
                 
                  1 
               
               
                 peptide 
                 
                   ATGGCTCGCTCGGTGACCCTGGTCTTTCTGGTGCTTGTCTCACTGACCGGCCTGTAT 
                 
                  2 
               
               
                 of β 2   
                 
                   GCT 
                 
                   
               
               
                 micro- 
                   
                   
               
               
                 globulin 
                   
                   
               
               
                   
               
               
                 OVA 
                 SIINFEKL 
                  3 
               
               
                 peptide 
                 TCCATTATAAATTTTGAAAAGTTG 
                  4 
               
               
                 1 (for 
                   
                   
               
               
                 MHC 
                   
                   
               
               
                 class I 
                   
                   
               
               
                 molecule) 
                   
                   
               
               
                   
               
               
                 Peptide  
                 GGGASGGGGSGGGGS 
                  5 
               
               
                 linker 1 
                 GGCGGAGGTGCCTCTGGCGGTGGGGGCAGCGGTGGAGGGGGCAGT 
                  6 
               
               
                   
               
               
                 β 2   
                 IQKTPQIQVYSRHPPENGKPNILNCYVTQFHPPHIEIQMLKNGKKIPKVEMSDMSFS 
                  7 
               
               
                 Micro- 
                 KDWSFYILAHTEFTPTETDTYACRVKHASMAEPKTVYWDRDM 
                   
               
               
                 globulin 
                 ATCCAGAAAACCCCTCAAATTCAAGTATACTCACGCCACCCACCGGAGAATGGGAAG 
                   
               
               
                 (from 
                 CCGAACATACTGAACTGCTACGTAACACAGTTCCACCCGCCTCACATTGAAATCCAA 
                   
               
               
                 which 
                 ATGCTGAAGAACGGGAAAAAAATTCCTAAAGTAGAGATGTCAGATATGTCCTTCAGC 
                  8 
               
               
                 signal  
                 AAGGACTGGTCTTTCTATATCCTGGCTCACACTGAATTCACCCCCACTGAGACTGAT 
                   
               
               
                 peptide 
                 ACATACGCCTGCAGAGTTAAGCATGCCAGTATGGCCGAGCCCAAGACCGTCTACTGG 
                   
               
               
                 is 
                 GATCGAGACATG 
                   
               
               
                 removed) 
                   
                   
               
               
                   
               
               
                 MHC  
                 GPHSLRYFVTAVSRPGLGEPRYMEVGYVDDTEFVRFDSDAENPRYEPRARWMEQEGP 
                  9 
               
               
                 class Iα 
                 EYWERETQKAKGNEQSFRVDLRTLLGYYNQSKGGSHTIQVISGCEVGSDGRLLRGYQ 
                   
               
               
                 chain 
                 QYAYDGCDYIALNEDLKTWTAADMAALITKHKWEQAGEAERLRAYLEGTCVEWLRRY 
                   
               
               
                 (from  
                 LKNGNATLLRTDSPKAHVTHHSRPEDKVTLRCWALGFYPADITLTWQLNGEELIQDM 
                   
               
               
                 which 
                 ELYETRPAGDGTFQKWASVVVPLGKEQYYTCHVYHQGLPEPLTLRWEPPPSTVSNMA 
                   
               
               
                 signal  
                 TVAVLVVLGAAIVTGAVVAFVMKMRRRNTGGKGGDYALAPGSQTSDLSLPDCKVMVH 
                   
               
               
                 peptide 
                 DPHSLA 
                   
               
               
                 is  
                 GGCCCACACTCGCTGAGGTATTTCGTCACCGCCGTGTCCCGGCCCGGCCTCGGGGAG 
                 10 
               
               
                 removed) 
                 CCCCGGTACATGGAAGTCGGCTACGTGGACGACACGGAGTTCGTGCGCTTCGACAGC 
                   
               
               
                   
                 GACGCGGAGAATCCGAGATATGAGCCGCGGGCGCGGTGGATGGAGCAGGAGGGGCCC 
                   
               
               
                   
                 GAGTATTGGGAGCGGGAGACACAGAAAGCCAAGGGCAATGAGCAGAGTTTCCGAGTG 
                   
               
               
                   
                 GACCTGAGGACCCTGCTCGGCTACTACAACCAGAGCAAGGGCGGCTCTCACACTATT 
                   
               
               
                   
                 CAGGTGATCTCTGGCTGTGAAGTGGGGTCCGACGGGCGACTCCTCCGCGGGTACCAG 
                   
               
               
                   
                 CAGTACGCCTACGACGGCTGCGATTACATCGCCCTGAACGAAGACCTGAAAACGTGG 
                   
               
               
                   
                 ACGGCGGCGGACATGGCGGCGCTGATCACCAAACACAAGTGGGAGCAGGCTGGTGAA 
                   
               
               
                   
                 GCAGAGAGACTCAGGGCCTACCTGGAGGGCACGTGCGTGGAGTGGCTCCGCAGATAC 
                   
               
               
                   
                 CTGAAGAACGGGAACGCGACGCTGCTGCGCACAGATTCCCCAAAGGCCCATGTGACC 
                   
               
               
                   
                 CATCACAGCAGACCTGAAGATAAAGTCACCCTGAGGTGCTGGGCCCTGGGCTTCTAC 
                   
               
               
                   
                 CCTGCTGACATCACCCTGACCTGGCAGTTGAATGGGGAGGAGCTGATCCAGGACATG 
                   
               
               
                   
                 GAGCTTGTGGAGACCAGGCCTGCAGGGGATGGAACCTTCCAGAAGTGGGCATCTGTG 
                   
               
               
                   
                 GTGGTGCCTCTTGGGAAGGAGCAGTATTACACATGCCATGTGTACCATCAGGGGCTG 
                   
               
               
                   
                 CCTGAGCCCCTCACCCTGAGATGGGAGCCTCCTCCATCCACTGTCTCCAACATGGCG 
                   
               
               
                   
                 ACCGTTGCTGTTCTGGTTGTCCTTGGAGCTGCAATAGTCACTGGAGCTGTGGTGGCT 
                   
               
               
                   
                 TTTGTGATGAAGATGAGAAGGAGAAACACAGGTGGAAAAGGAGGGGACTATGCTCTG 
                   
               
               
                   
                 GCTCCAGGCTCCCAGACCTCTGATCTGTCTCTCCCAGATTGTAAAGTGATGGTTCAT 
                   
               
               
                   
                 GACCCTCATTCTCTAGCG 
                   
               
               
                   
               
               
                 Peptide  
                 GGGGSGGGGSGGGGSGGGGS 
                 11 
               
               
                 linker 2 
                 GGGGGGGGAGGCTCCGGTGGAGGGGGGTCTGGAGGGGGGGGGTCTGGTGGAGGCGGA 
                 12 
               
               
                   
                 AGT 
                   
               
               
                   
               
               
                 Single  
                 IQKTPQIQVYSRHPPENGKPNILNCYVTQFHPPHIEIQMLKNGKKIPKVEMSDMSFS 
                 65 
               
               
                 chain 
                 KDWSFYILAHTEFTPTETDTYACRVKHASMAEPKTVYWDRDMGGGGSGGGGSGGGGS 
                   
               
               
                 MHC  
                 GGGGSGPHSLRYFVTAVSRPGLGEPRYMEVGYVDDTEFVRFDSDAENPRYEPRARWM 
                   
               
               
                 class I 
                 EQEGPEYWERETQKAKGNEQSFRVDLRTLLGYYNQSKGGSHTIQVISGCEVGSDGRL 
                   
               
               
                 molecule 
                 LRGYQQYAYDGCDYIALNEDLKTWTAADMAALITKHKWEQAGEAERLRAYLEGTCVE 
                   
               
               
                 (β 2   
                 WLRRYLKNGNATLLRTDSPKAHVTHHSRPEDKVTLRCWALGFYPADITLTWQLNGEE 
                   
               
               
                 micro- 
                 LIQDMELVETRPAGDGTFQKWASVVVPLGKEQYYTCHVYHQGLPEPLTLRWEPPPST 
                   
               
               
                 globulin 
                 VSNMATVAVLVVLGAAIVTGAVVAFVMKMRRRNTGGKGGDYALAPGSQTSDLSLPDC 
                   
               
               
                 (from  
                 KVMVHDPHSLA 
                   
               
               
                 which 
                 ATCCAGAAAACCCCTCAAATTCAAGTATACTCACGCCACCCACCGGAGAATGGGAAG 
                 66 
               
               
                 signal  
                 CCGAACATACTGAACTGCTACGTAACACAGTTCCACCCGCCTCACATTGAAATCCAA 
                   
               
               
                 peptide 
                 ATGCTGAAGAACGGGAAAAAAATTCCTAAAGTAGAGATGTCAGATATGTCCTTCAGC 
                   
               
               
                 is re- 
                 AAGGACTGGTCTTTCTATATCCTGGCTCACACTGAATTCACCCCCACTGAGACTGAT 
                   
               
               
                 moved) + 
                 ACATACGCCTGCAGAGTTAAGCATGCCAGTATGGCCGAGCCCAAGACCGTCTACTGG 
                   
               
               
                 peptide  
                 GATCGAGACATGGGGGGGGGAGGCTCCGGTGGAGGGGGGTCTGGAGGGGGGGGGTCT 
                   
               
               
                 linker 2 + 
                 GGTGGAGGCGGAAGTGGCCCACACTCGCTGAGGTATTTCGTCACCGCCGTGTCCCGG 
                   
               
               
                 MHC class 
                 CCCGGCCTCGGGGAGCCCCGGTACATGGAAGTCGGCTACGTGGACGACACGGAGTTC 
                   
               
               
                 Iα chain 
                 GTGCGCTTCGACAGCGACGCGGAGAATCCGAGATATGAGCCGCGGGCGCGGTGGATG 
                   
               
               
                 (from  
                 GAGCAGGAGGGGCCCGAGTATTGGGAGCGGGAGACACAGAAAGCCAAGGGCAATGAG 
                   
               
               
                 which 
                 CAGAGTTTCCGAGTGGACCTGAGGACCCTGCTCGGCTACTACAACCAGAGCAAGGGC 
                   
               
               
                 signal  
                 GGCTCTCACACTATTCAGGTGATCTCTGGCTGTGAAGTGGGGTCCGACGGGCGACTC 
                   
               
               
                 peptide 
                 CTCCGCGGGTACCAGCAGTACGCCTACGACGGCTGCGATTACATCGCCCTGAACGAA 
                   
               
               
                 is  
                 GACCTGAAAACGTGGACGGCGGCGGACATGGCGGCGCTGATCACCAAACACAAGTGG 
                   
               
               
                 removed)) 
                 GAGCAGGCTGGTGAAGCAGAGAGACTCAGGGCCTACCTGGAGGGCACGTGCGTGGAG 
                   
               
               
                   
                 TGGCTCCGCAGATACCTGAAGAACGGGAACGCGACGCTGCTGCGCACAGATTCCCCA 
                   
               
               
                   
                 AAGGCCCATGTGACCCATCACAGCAGACCTGAAGATAAAGTCACCCTGAGGTGCTGG 
                   
               
               
                   
                 GCCCTGGGCTTCTACCCTGCTGACATCACCCTGACCTGGCAGTTGAATGGGGAGGAG 
                   
               
               
                   
                 CTGATCCAGGACATGGAGCTTGTGGAGACCAGGCCTGCAGGGGATGGAACCTTCCAG 
                   
               
               
                   
                 AAGTGGGCATCTGTGGTGGTGCCTCTTGGGAAGGAGCAGTATTACACATGCCATGTG 
                   
               
               
                   
                 TACCATCAGGGGCTGCCTGAGCCCCTCACCCTGAGATGGGAGCCTCCTCCATCCACT 
                   
               
               
                   
                 GTCTCCAACATGGCGACCGTTGCTGTTCTGGTTGTCCTTGGAGCTGCAATAGTCACT 
                   
               
               
                   
                 GGAGCTGTGGTGGCTTTTGTGATGAAGATGAGAAGGAGAAACACAGGTGGAAAAGGA 
                   
               
               
                   
                 GGGGACTATGCTCTGGCTCCAGGCTCCCAGACCTCTGATCTGTCTCTCCCAGATTGT 
                   
               
               
                   
                 AAAGTGATGGTTCATGACCCTCATTCTCTAGCG 
                   
               
               
                   
               
               
                 sc-   
                   MARSVTLVFLVLVSLTGLYA SIINFEKLGGGASGGGGSGGGGSIQKTPQIQVYSRHP 
                 13 
               
               
                 Trimer 
                 PENGKPNILNCYVTQFHPPHIEIQMLKNGKKIPKVEMSDMSFSKDWSFYILAHTEFT 
                   
               
               
                 (OVA  
                 PTETDTYACRVKHASMAEPKTVYTDRDMGGGGSGGGGSGGGGSGGGGSGPHSLRYFV 
                   
               
               
                 peptide 1 + 
                 TAVSRPGLGEPRYMEVGYVDDTEFVRFDSDAENPRYEPRARWMEQEGPEYWERETQK 
                   
               
               
                 peptide 
                 AKGNEQSFRVDLRTLLGYYNQSKGGSHTIQVISGCEVGSDGRLLRGYQQYAYDGCDY 
                   
               
               
                 linker 1 + 
                 IALNEDLKTWTAADMAALITKHKWEQAGEAERLRAYLEGTCVEWLRRYLKNGNATLL 
                   
               
               
                 single  
                 RTDSPKAHVTHHSRPEDKVTLRCWALGFYPADITLTWQLNGEELIQDMELVETRPAG 
                   
               
               
                 chain 
                 DGTFQKWASVVVPLGKEQYYTCHVYHQGLPEPLTLRWEPPPSTVSNMATVAVLVVLG 
                   
               
               
                 MHC class 
                 AAIVTGAVVAFVMKMRRRNTGGKGGDYALAPGSQTSDLSLPDCKVMVHDPHSLA 
                   
               
               
                 1  
                 
                   ATGGCTCGCTCGGTGACCCTGGTCTTTCTGGTGCTTGTCTCACTGACCGGCCTGTAT 
                 
                 14 
               
               
                 molecule) 
                   GCT TCCATTATAAATTTTGAAAAGTTGGGCGGAGGTGCCTCTGGCGGTGGGGGCAGC 
                   
               
               
                   
                 GGTGGAGGGGGCAGTATCCAGAAAACCCCTCAAATTCAAGTATACTCACGCCACCCA 
                   
               
               
                   
                 CCGGAGAATGGGAAGCCGAACATACTGAACTGCTACGTAACACAGTTCCACCCGCCT 
                   
               
               
                   
                 CACATTGAAATCCAAATGCTGAAGAACGGGAAAAAAATTCCTAAAGTAGAGATGTCA 
                   
               
               
                   
                 GATATGTCCTTCAGCAAGGACTGGTCTTTCTATATCCTGGCTCACACTGAATTCACC 
                   
               
               
                   
                 CCCACTGAGACTGATACATACGCCTGCAGAGTTAAGCATGCCAGTATGGCCGAGCCC 
                   
               
               
                   
                 AAGACCGTCTACTGGGATCGAGACATGGGGGGGGGAGGCTCCGGTGGAGGGGGGTCT 
                   
               
               
                   
                 GGAGGGGGGGGGTCTGGTGGAGGCGGAAGTGGCCCACACTCGCTGAGGTATTTCGTC 
                   
               
               
                   
                 ACCGCCGTGTCCCGGCCCGGCCTCGGGGAGCCCCGGTACATGGAAGTCGGCTACGTG 
                   
               
               
                   
                 GACGACACGGAGTTCGTGCGCTTCGACAGCGACGCGGAGAATCCGAGATATGAGCCG 
                   
               
               
                   
                 CGGGCGCGGTGGATGGAGCAGGAGGGGCCCGAGTATTGGGAGCGGGAGACACAGAAA 
                   
               
               
                   
                 GCCAAGGGCAATGAGCAGAGTTTCCGAGTGGACCTGAGGACCCTGCTCGGCTACTAC 
                   
               
               
                   
                 AACCAGAGCAAGGGCGGCTCTCACACTATTCAGGTGATCTCTGGCTGTGAAGTGGGG 
                   
               
               
                   
                 TCCGACGGGCGACTCCTCCGCGGGTACCAGCAGTACGCCTACGACGGCTGCGATTAC 
                   
               
               
                   
                 ATCGCCCTGAACGAAGACCTGAAAACGTGGACGGCGGCGGACATGGCGGCGCTGATC 
                   
               
               
                   
                 ACCAAACACAAGTGGGAGCAGGCTGGTGAAGCAGAGAGACTCAGGGCCTACCTGGAG 
                   
               
               
                   
                 GGCACGTGCGTGGAGTGGCTCCGCAGATACCTGAAGAACGGGAACGCGACGCTGCTG 
                   
               
               
                   
                 CGCACAGATTCCCCAAAGGCCCATGTGACCCATCACAGCAGACCTGAAGATAAAGTC 
                   
               
               
                   
                 ACCCTGAGGTGCTGGGCCCTGGGCTTCTACCCTGCTGACATCACCCTGACCTGGCAG 
                   
               
               
                   
                 TTGAATGGGGAGGAGCTGATCCAGGACATGGAGCTTGTGGAGACCAGGCCTGCAGGG 
                   
               
               
                   
                 GATGGAACCTTCCAGAAGTGGGCATCTGTGGTGGTGCCTCTTGGGAAGGAGCAGTAT 
                   
               
               
                   
                 TACACATGCCATGTGTACCATCAGGGGCTGCCTGAGCCCCTCACCCTGAGATGGGAG 
                   
               
               
                   
                 CCTCCTCCATCCACTGTCTCCAACATGGCGACCGTTGCTGTTCTGGTTGTCCTTGGA 
                   
               
               
                   
                 GCTGCAATAGTCACTGGAGCTGTGGTGGCTTTTGTGATGAAGATGAGAAGGAGAAAC 
                   
               
               
                   
                 ACAGGTGGAAAAGGAGGGGACTATGCTCTGGCTCCAGGCTCCCAGACCTCTGATCTG 
                   
               
               
                   
                 TCTCTCCCAGATTGTAAAGTGATGGTTCATGACCCTCATTCTCTAGCG 
                   
               
               
                   
               
               
                 CD81 
                 MGVEGCTKCIKYLLFVFNFVFWLAGGVILGVALWLRHDPQTTSLLYLELGNKPAPNT 
                 15 
               
               
                   
                 FYVGIYILIAVGAVMMFVGFLGCYGAIQESQCLLGTFFTCLVILFACEVAAGIWGFV 
                   
               
               
                   
                 NKDQIAKDVKQFYDQALQQAVMDDDANNAKAVVKTFHETLNCCGSNALTTLTTTILR 
                   
               
               
                   
                 NSLCPSGGNILTPLLQQDCHQKIDELFSGKLYLIGIAAIVVAVIMIFEMILSMVLCC 
                   
               
               
                   
                 GIRNSSVY 
                   
               
               
                   
                 ATGGGGGTGGAGGGCTGCACCAAATGCATCAAATACCTGCTCTTCGTCTTCAATTTC 
                 16 
               
               
                   
                 GTCTTCTGGCTGGCTGGAGGCGTGATCCTAGGTGTAGCTCTGTGGTTGCGTCATGAT 
                   
               
               
                   
                 CCACAGACCACCAGCCTGCTGTACCTGGAACTGGGAAACAAACCGGCACCCAACACC 
                   
               
               
                   
                 TTCTACGTGGGCATCTACATTCTCATTGCTGTGGGAGCTGTGATGATGTTTGTAGGC 
                   
               
               
                   
                 TTCCTGGGGTGCTATGGGGCCATCCAGGAGTCCCAGTGTCTGCTGGGGACGTTCTTC 
                   
               
               
                   
                 ACCTGCCTTGTGATCCTGTTTGCCTGTGAGGTGGCTGCAGGCATCTGGGGCTTCGTA 
                   
               
               
                   
                 AACAAAGACCAGATCGCCAAGGATGTGAAGCAGTTCTATGACCAGGCCCTTCAGCAA 
                   
               
               
                   
                 GCTGTGATGGATGATGATGCCAACAATGCCAAGGCTGTGGTGAAGACTTTCCATGAG 
                   
               
               
                   
                 ACGCTCAACTGTTGTGGCTCCAACGCACTGACCACACTGACTACCACCATACTGAGG 
                   
               
               
                   
                 AACAGCCTGTGTCCCTCAGGCGGCAACATACTCACCCCCTTACTGCAGCAAGATTGT 
                   
               
               
                   
                 CATCAGAAAATCGATGAGCTCTTCTCTGGGAAGCTGTACCTCATTGGAATTGCAGCC 
                   
               
               
                   
                 ATTGTGGTAGCTGTCATTATGATCTTTGAGATGATTCTGAGCATGGTGCTGTGCTGT 
                   
               
               
                   
                 GGCATCCGGAACAGCTCCGTGTACTGA 
                   
               
               
                   
               
               
                 sc-  
                   MARSVTLVFLVLVSLTGLYA SIINFEKLGGGASGGGGSGGGGSIQKTPQIQVYSRHP 
                 17 
               
               
                 Trimer- 
                 PENGKPNILNCYVTQFHPPHIEIQMLKNGKKIPKVEMSDMSFSKDWSFYILAHTEFT 
                   
               
               
                 CD81 
                 PTETDTYACRVKHASMAEPKTVYWDRDMGGGGSGGGGSGGGGSGGGGSGPHSLRYFV 
                   
               
               
                 (sc- 
                 TAVSRPGLGEPRYMEVGYVDDTEFVRFDSDAENPRYEPRARWMEQEGPEYWERETQK 
                   
               
               
                 Trimer + 
                 AKGNEQSFRVDLRTLLGYYNQSKGGSHTIQVISGCEVGSDGRLLRGYQQYAYDGCDY 
                   
               
               
                 CD81) 
                 IALNEDLKTWTAADMAALITKHKWEQAGEAERLRAYLEGTCVEWLRRYLKNGNATLL 
                   
               
               
                   
                 RTDSPKAHVTHHSRPEDKVTLRCWALGFYPADITLTWQLNGEELIQDMELVETRPAG 
                   
               
               
                   
                 DGTFQKWASVVVPLGKEQYYTCHVYHQGLPEPLTLRWEPPPSTVSNMATVAVLVVLG 
                   
               
               
                   
                 AAIVTGAVVAFVMKMRRRNTGGKGGDYALAPGSQTSDLSLPDCKVMVHDPHSLAMGV 
                   
               
               
                   
                 EGCTKCIKYLLFVFNFVFWLAGGVILGVALWLRHDPQTTSLLYLELGNKPAPNTFYV 
                   
               
               
                   
                 GIYILIAVGAVMMFVGFLGCYGAIQESQCLLGTFFTCLVILFACEVAAGIWGFVNKD 
                   
               
               
                   
                 QIAKDVKQFYDQALQQAVMDDDANNAKAVVKTFHETLNCCGSNALTTLTTTILRNSL 
                   
               
               
                   
                 CPSGGNILTPLLQQDCHQKIDELFSGKLYLIGIAAIVVAVIMIFEMILSMVLCCGIR 
                   
               
               
                   
                 NSSVY 
                   
               
               
                   
                 
                   ATGGCTCGCTCGGTGACCCTGGTCTTTCTGGTGCTTGTCTCACTGACCGGCCTGTAT 
                 
                 18 
               
               
                   
                   GCT TCCATTATAAATTTTGAAAAGTTGGGCGGAGGTGCCTCTGGCGGTGGGGGCAGC 
                   
               
               
                   
                 GGTGGAGGGGGCAGTATCCAGAAAACCCCTCAAATTCAAGTATACTCACGCCACCCA 
                   
               
               
                   
                 CCGGAGAATGGGAAGCCGAACATACTGAACTGCTACGTAACACAGTTCCACCCGCCT 
                   
               
               
                   
                 CACATTGAAATCCAAATGCTGAAGAACGGGAAAAAAATTCCTAAAGTAGAGATGTCA 
                   
               
               
                   
                 GATATGTCCTTCAGCAAGGACTGGTCTTTCTATATCCTGGCTCACACTGAATTCACC 
                   
               
               
                   
                 CCCACTGAGACTGATACATACGCCTGCAGAGTTAAGCATGCCAGTATGGCCGAGCCC 
                   
               
               
                   
                 AAGACCGTCTACTGGGATCGAGACATGGGGGGGGGAGGCTCCGGTGGAGGGGGGTCT 
                   
               
               
                   
                 GGAGGGGGGGGGTCTGGTGGAGGCGGAAGTGGCCCACACTCGCTGAGGTATTTCGTC 
                   
               
               
                   
                 ACCGCCGTGTCCCGGCCCGGCCTCGGGGAGCCCCGGTACATGGAAGTCGGCTACGTG 
                   
               
               
                   
                 GACGACACGGAGTTCGTGCGCTTCGACAGCGACGCGGAGAATCCGAGATATGAGCCG 
                   
               
               
                   
                 CGGGCGCGGTGGATGGAGCAGGAGGGGCCCGAGTATTGGGAGCGGGAGACACAGAAA 
                   
               
               
                   
                 GCCAAGGGCAATGAGCAGAGTTTCCGAGTGGACCTGAGGACCCTGCTCGGCTACTAC 
                   
               
               
                   
                 AACCAGAGCAAGGGCGGCTCTCACACTATTCAGGTGATCTCTGGCTGTGAAGTGGGG 
                   
               
               
                   
                 TCCGACGGGCGACTCCTCCGCGGGTACCAGCAGTACGCCTACGACGGCTGCGATTAC 
                   
               
               
                   
                 ATCGCCCTGAACGAAGACCTGAAAACGTGGACGGCGGCGGACATGGCGGCGCTGATC 
                   
               
               
                   
                 ACCAAACACAAGTGGGAGCAGGCTGGTGAAGCAGAGAGACTCAGGGCCTACCTGGAG 
                   
               
               
                   
                 GGCACGTGCGTGGAGTGGCTCCGCAGATACCTGAAGAACGGGAACGCGACGCTGCTG 
                   
               
               
                   
                 CGCACAGATTCCCCAAAGGCCCATGTGACCCATCACAGCAGACCTGAAGATAAAGTC 
                   
               
               
                   
                 ACCCTGAGGTGCTGGGCCCTGGGCTTCTACCCTGCTGACATCACCCTGACCTGGCAG 
                   
               
               
                   
                 TTGAATGGGGAGGAGCTGATCCAGGACATGGAGCTTGTGGAGACCAGGCCTGCAGGG 
                   
               
               
                   
                 GATGGAACCTTCCAGAAGTGGGCATCTGTGGTGGTGCCTCTTGGGAAGGAGCAGTAT 
                   
               
               
                   
                 TACACATGCCATGTGTACCATCAGGGGCTGCCTGAGCCCCTCACCCTGAGATGGGAG 
                   
               
               
                   
                 CCTCCTCCATCCACTGTCTCCAACATGGCGACCGTTGCTGTTCTGGTTGTCCTTGGA 
                   
               
               
                   
                 GCTGCAATAGTCACTGGAGCTGTGGTGGCTTTTGTGATGAAGATGAGAAGGAGAAAC 
                   
               
               
                   
                 ACAGGTGGAAAAGGAGGGGACTATGCTCTGGCTCCAGGCTCCCAGACCTCTGATCTG 
                   
               
               
                   
                 TCTCTCCCAGATTGTAAAGTGATGGTTCATGACCCTCATTCTCTAGCGATGGGGGTG 
                   
               
               
                   
                 GAGGGCTGCACCAAATGCATCAAATACCTGCTCTTCGTCTTCAATTTCGTCTTCTGG 
                   
               
               
                   
                 CTGGCTGGAGGCGTGATCCTAGGTGTAGCTCTGTGGTTGCGTCATGATCCACAGACC 
                   
               
               
                   
                 ACCAGCCTGCTGTACCTGGAACTGGGAAACAAACCGGCACCCAACACCTTCTACGTG 
                   
               
               
                   
                 GGCATCTACATTCTCATTGCTGTGGGAGCTGTGATGATGTTTGTAGGCTTCCTGGGG 
                   
               
               
                   
                 TGCTATGGGGCCATCCAGGAGTCCCAGTGTCTGCTGGGGACGTTCTTCACCTGCCTT 
                   
               
               
                   
                 GTGATCCTGTTTGCCTGTGAGGTGGCTGCAGGCATCTGGGGCTTCGTAAACAAAGAC 
                   
               
               
                   
                 CAGATCGCCAAGGATGTGAAGCAGTTCTATGACCAGGCCCTTCAGCAAGCTGTGATG 
                   
               
               
                   
                 GATGATGATGCCAACAATGCCAAGGCTGTGGTGAAGACTTTCCATGAGACGCTCAAC 
                   
               
               
                   
                 TGTTGTGGCTCCAACGCACTGACCACACTGACTACCACCATACTGAGGAACAGCCTG 
                   
               
               
                   
                 TGTCCCTCAGGCGGCAACATACTCACCCCCTTACTGCAGCAAGATTGTCATCAGAAA 
                   
               
               
                   
                 ATCGATGAGCTCTTCTCTGGGAAGCTGTACCTCATTGGAATTGCAGCCATTGTGGTA 
                   
               
               
                   
                 GCTGTCATTATGATCTTTGAGATGATTCTGAGCATGGTGCTGTGCTGTGGCATCCGG 
                   
               
               
                   
                 AACAGCTCCGTGTACTGA 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
             
               
                 TABLE 2 
               
               
                   
               
               
                   
                   
                 SEQ 
               
               
                   
                   
                 ID 
               
               
                   
                 Sequence 
                 NO: 
               
               
                   
               
             
            
               
                 CD80 
                   MACNCQLMQDTPLLKFPCPRLILLFVLLIRLSQVSSD VDEQLSKSVKDKVLLPCRYN 
                 19 
               
               
                   
                 SPHEDESEDRIYWQKHDKVVLSVIAGKLKVWPEYKNRTLYDNTTYSLIILGLVLSDR 
                   
               
               
                   
                 GTYSCVVQKKERGTYEVKHLALVKLSIKADFSTPNITESGNPSADTKRITCFASGGF 
                   
               
               
                   
                 PKPRFSWLENGRELPGINTTISQDPESELYTISSQLDFNTTRNHTIKCLIKYGDAHV 
                   
               
               
                   
                 SEDFTWEKPPEDPPDSKNTLVLFGAGFGAVITVVVIVVIIKCFCKHRSCFRRNEASR 
                   
               
               
                   
                 ETNNSLTFGPEEALAEQTVFL 
                   
               
               
                   
                 
                   ATGGCTTGCAATTGTCAGTTGATGCAGGATACACCACTCCTCAAGTTTCCATGTCCA 
                 
                 20 
               
               
                   
                   AGGCTCATTCTTCTCTTTGTGCTGCTGATTCGTCTTTCACAAGTGTCTTCAGAT GTT 
                   
               
               
                   
                 GATGAACAACTGTCCAAGTCAGTGAAAGATAAGGTATTGCTGCCTTGCCGTTACAAC 
                   
               
               
                   
                 TCTCCTCATGAAGATGAGTCTGAAGACCGAATCTACTGGCAAAAACATGACAAAGTG 
                   
               
               
                   
                 GTGCTGTCTGTCATTGCTGGGAAACTAAAAGTGTGGCCCGAGTATAAGAACCGGACT 
                   
               
               
                   
                 TTATATGACAACACTACCTACTCTCTTATCATCCTGGGCCTGGTCCTTTCAGACCGG 
                   
               
               
                   
                 GGCACATACAGCTGTGTCGTTCAAAAGAAGGAAAGAGGAACGTATGAAGTTAAACAC 
                   
               
               
                   
                 TTGGCTTTAGTAAAGTTGTCCATCAAAGCTGACTTCTCTACCCCCAACATAACTGAG 
                   
               
               
                   
                 TCTGGAAACCCATCTGCAGACACTAAAAGGATTACCTGCTTTGCTTCCGGGGGTTTC 
                   
               
               
                   
                 CCAAAGCCTCGCTTCTCTTGGTTGGAAAATGGAAGAGAATTACCTGGCATCAATACG 
                   
               
               
                   
                 ACAATTTCCCAGGATCCTGAATCTGAATTGTACACCATTAGTAGCCAACTAGATTTC 
                   
               
               
                   
                 AATACGACTCGCAACCACACCATTAAGTGTCTCATTAAATATGGAGATGCTCACGTG 
                   
               
               
                   
                 TCAGAGGACTTCACCTGGGAAAAACCCCCAGAAGACCCTCCTGATAGCAAGAACACA 
                   
               
               
                   
                 CTTGTGCTCTTTGGGGCAGGATTCGGCGCAGTAATAACAGTCGTCGTCATCGTTGTC 
                   
               
               
                   
                 ATCATCAAATGCTTCTGTAAGCACAGAAGCTGTTTCAGAAGAAATGAGGCAAGCAGA 
                   
               
               
                   
                 GAAACAAACAACAGCCTTACCTTCGGGCCTGAAGAAGCATTAGCTGAACAGACCGTC 
                   
               
               
                   
                 TTCCTTTAG 
                   
               
               
                   
               
               
                 CD9 
                 MPVKGGSKCIKYLLFGFNFIFWLAGIAVLAIGLWLRFDSQTKSIFEQENNHSSFYTG 
                 21 
               
               
                   
                 VYILIGAGALMMLVGFLGCCGAVQESQCMLGLFFGFLLVIFAIEIAAAVWGYTHKDE 
                   
               
               
                   
                 VIKELQEFYKDTYQKLRSKDEPQRETLKAIHMALDCCGIAGPLEQFISDTCPKKQLL 
                   
               
               
                   
                 ESFQVKPCPEAISEVFNNKFHIIGAVGIGIAVVMIFGMIFSMILCCAIRRSREMV 
                   
               
               
                   
                 ATGCCGGTCAAAGGAGGTAGCAAGTGCATCAAATACCTGCTCTTCGGATTTAACTTC 
                 22 
               
               
                   
                 ATCTTCTGGCTCGCTGGCATTGCAGTGCTTGCTATTGGACTATGGCTCCGATTCGAC 
                   
               
               
                   
                 TCTCAGACCAAGAGCATCTTCGAGCAAGAGAATAACCATTCCAGTTTCTACACAGGA 
                   
               
               
                   
                 GTGTACATTCTGATTGGAGCCGGGGCCCTCATGATGCTGGTTGGTTTCCTGGGCTGC 
                   
               
               
                   
                 TGTGGAGCTGTACAAGAGTCCCAGTGCATGCTGGGATTGTTCTTCGGGTTCCTCTTG 
                   
               
               
                   
                 GTGATATTCGCCATTGAGATAGCCGCCGCCGTCTGGGGCTATACCCACAAGGATGAG 
                   
               
               
                   
                 GTGATTAAAGAACTCCAGGAGTTTTACAAGGACACCTACCAAAAGTTACGGAGCAAG 
                   
               
               
                   
                 GATGAACCCCAGCGGGAAACACTCAAAGCCATCCATATGGCGTTGGACTGCTGTGGC 
                   
               
               
                   
                 ATAGCTGGTCCTTTGGAGCAGTTTATCTCGGACACCTGCCCCAAGAAACAGCTTTTG 
                   
               
               
                   
                 GAAAGTTTCCAGGTTAAGCCCTGCCCTGAAGCCATCAGTGAGGTCTTCAACAACAAG 
                   
               
               
                   
                 TTCCACATCATTGGAGCAGTGGGTATCGGCATCGCCGTGGTGATGATCTTCGGCATG 
                   
               
               
                   
                 ATCTTCAGCATGATCCTGTGCTGCGCCATCCGCAGGAGCCGAGAAATGGTCTAG 
                   
               
               
                   
               
               
                 CD80-  
                   MACNCQLMQDTPLLKFPCPRLILLFVLLIRLSQVSSD VDEQLSKSVKDKVLLPCRYN 
                 23 
               
               
                 CD9 
                 SPHEDESEDRIYWQKHDKVVLSVIAGKLKVWPEYKNRTLYDNTTYSLIILGLVLSDR 
                   
               
               
                   
                 GTYSCVVQKKERGTYEVKHLALVKLSIKADFSTPNITESGNPSADTKRITCFASGGF 
                   
               
               
                   
                 PKPRFSWLENGRELPGINTTISQDPESELYTISSQLDFNTTRNHTIKCLIKYGDAHV 
                   
               
               
                   
                 SEDFTWEKPPEDPPDSKNTLVLFGAGFGAVITVVVIVVIIKCFCKHRSCFRRNEASR 
                   
               
               
                   
                 ETNNSLTFGPEEALAEQTVFLMPVKGGSKCIKYLLFGFNFIFWLAGIAVLAIGLWLR 
                   
               
               
                   
                 FDSQTKSIFEQENNHSSFYTGVYILIGAGALMMLVGFLGCCGAVQESQCMLGLFFGF 
                   
               
               
                   
                 LLVIFAIEIAAAVWGYTHKDEVIKELQEFYKDTYQKLRSKDEPQRETLKAIHMALDC 
                   
               
               
                   
                 CGlAGPLEQFISDTCPKKQLLESFQVKPCPEAISEVFNNKFHIIGAVGIGIAVVMIF 
                   
               
               
                   
                 GMIFSMILCCAIRRSREMV 
                   
               
               
                   
                 
                   ATGGCTTGCAATTGTCAGTTGATGCAGGATACACCACTCCTCAAGTTTCCATGTCCA 
                 
                 24 
               
               
                   
                   AGGCTCATTCTTCTCTTTGTGCTGCTGATTCGTCTTTCACAAGTGTCTTCAGAT GTT 
                   
               
               
                   
                 GATGAACAACTGTCCAAGTCAGTGAAAGATAAGGTATTGCTGCCTTGCCGTTACAAC 
                   
               
               
                   
                 TCTCCTCATGAAGATGAGTCTGAAGACCGAATCTACTGGCAAAAACATGACAAAGTG 
                   
               
               
                   
                 GTGCTGTCTGTCATTGCTGGGAAACTAAAAGTGTGGCCCGAGTATAAGAACCGGACT 
                   
               
               
                   
                 TTATATGACAACACTACCTACTCTCTTATCATCCTGGGCCTGGTCCTTTCAGACCGG 
                   
               
               
                   
                 GGCACATACAGCTGTGTCGTTCAAAAGAAGGAAAGAGGAACGTATGAAGTTAAACAC 
                   
               
               
                   
                 TTGGCTTTAGTAAAGTTGTCCATCAAAGCTGACTTCTCTACCCCCAACATAACTGAG 
                   
               
               
                   
                 TCTGGAAACCCATCTGCAGACACTAAAAGGATTACCTGCTTTGCTTCCGGGGGTTTC 
                   
               
               
                   
                 CCAAAGCCTCGCTTCTCTTGGTTGGAAAATGGAAGAGAATTACCTGGCATCAATACG 
                   
               
               
                   
                 ACAATTTCCCAGGATCCTGAATCTGAATTGTACACCATTAGTAGCCAACTAGATTTC 
                   
               
               
                   
                 AATACGACTCGCAACCACACCATTAAGTGTCTCATTAAATATGGAGATGCTCACGTG 
                   
               
               
                   
                 TCAGAGGACTTCACCTGGGAAAAACCCCCAGAAGACCCTCCTGATAGCAAGAACACA 
                   
               
               
                   
                 CTTGTGCTCTTTGGGGCAGGATTCGGCGCAGTAATAACAGTCGTCGTCATCGTTGTC 
                   
               
               
                   
                 ATCATCAAATGCTTCTGTAAGCACAGAAGCTGTTTCAGAAGAAATGAGGCAAGCAGA 
                   
               
               
                   
                 GAAACAAACAACAGCCTTACCTTCGGGCCTGAAGAAGCATTAGCTGAACAGACCGTC 
                   
               
               
                   
                 TTCCTTATGCCGGTCAAAGGAGGTAGCAAGTGCATCAAATACCTGCTCTTCGGATTT 
                   
               
               
                   
                 AACTTCATCTTCTGGCTCGCTGGCATTGCAGTGCTTGCTATTGGACTATGGCTCCGA 
                   
               
               
                   
                 TTCGACTCTCAGACCAAGAGCATCTTCGAGCAAGAGAATAACCATTCCAGTTTCTAC 
                   
               
               
                   
                 ACAGGAGTGTACATTCTGATTGGAGCCGGGGCCCTCATGATGCTGGTTGGTTTCCTG 
                   
               
               
                   
                 GGCTGCTGTGGAGCTGTACAAGAGTCCCAGTGCATGCTGGGATTGTTCTTCGGGTTC 
                   
               
               
                   
                 CTCTTGGTGATATTCGCCATTGAGATAGCCGCCGCCGTCTGGGGCTATACCCACAAG 
                   
               
               
                   
                 GATGAGGTGATTAAAGAACTCCAGGAGTTTTACAAGGACACCTACCAAAAGTTACGG 
                   
               
               
                   
                 AGCAAGGATGAACCCCAGCGGGAAACACTCAAAGCCATCCATATGGCGTTGGACTGC 
                   
               
               
                   
                 TGTGGCATAGCTGGTCCTTTGGAGCAGTTTATCTCGGACACCTGCCCCAAGAAACAG 
                   
               
               
                   
                 CTTTTGGAAAGTTTCCAGGTTAAGCCCTGCCCTGAAGCCATCAGTGAGGTCTTCAAC 
                   
               
               
                   
                 AACAAGTTCCACATCATTGGAGCAGTGGGTATCGGCATCGCCGTGGTGATGATCTTC 
                   
               
               
                   
                 GGCATGATCTTCAGCATGATCCTGTGCTGCGCCATCCGCAGGAGCCGAGAAATGGTC 
                   
               
               
                   
                 TAG 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
             
               
                 TABLE 3 
               
               
                   
               
               
                   
                   
                 SEQ 
               
               
                   
                   
                 ID  
               
               
                   
                 Sequence 
                 NO: 
               
               
                   
               
             
            
               
                 IL-2 
                 APTSSSTSSSTAEAQQQQQQQQQQQQHLEQLLMDLQELLSRMENYRNLKLPRMLTFK 
                 25 
               
               
                 (from 
                 FYLPKQATELKDLQCLEDELGPLRHVLDLTQSKSFQLEDAENFISNIRVTVVKLKGS 
                   
               
               
                 which 
                 DNTFECQFDDESATVVDFLRRWIAFCQSIISTSPQ 
                   
               
               
                 signal 
                 GCACCCACTTCAAGCTCCACTTCAAGCTCTACAGCGGAAGCACAGCAGCAGCAGCAG 
                 26 
               
               
                 peptide 
                 CAGCAGCAGCAGCAGCAGCAGCACCTGGAGCAGCTGTTGATGGACCTACAGGAGCTC 
                   
               
               
                 is  
                 CTGAGCAGGATGGAGAATTACAGGAACCTGAAACTCCCCAGGATGCTCACCTTCAAA 
                   
               
               
                 removed) 
                 TTTTACTTGCCCAAGCAGGCCACAGAATTGAAAGATCTTCAGTGCCTAGAAGATGAA 
                   
               
               
                   
                 CTTGGACCTCTGCGGCATGTTCTGGATTTGACTCAAAGCAAAAGCTTTCAATTGGAA 
                   
               
               
                   
                 GATGCTGAGAATTTCATCAGCAATATCAGAGTAACTGTTGTAAAACTAAAGGGCTCT 
                   
               
               
                   
                 GACAACACATTTGAGTGCCAATTCGATGATGAGTCAGCAACTGTGGTGGACTTTCTG 
                   
               
               
                   
                 AGGAGATGGATAGCCTTCTGTCAAAGCATCATCTCAACAAGCCCTCAA 
                   
               
               
                   
               
               
                 CD63 
                 MAVEGGMKCVKFLLYVLLLAFCACAVGLIAIGVAVQVVLKQAITHETTAGSLLPVVI 
                 27 
               
               
                   
                 IAVGAFLFLVAFVGCCGACKENYCLMITFAIFLSLIMLVEVAVAIAGYVFRDQVKSE 
                   
               
               
                   
                 FNKSFQQQMQNYLKDNKTATILDKLQKENNCCGASNYTDWENIPGMAKDRVPDSCCI 
                   
               
               
                   
                 NITVGCGNDFKESTIHTQGCVETIAIWLRKNILLVAAAALGIAFVEVLGIIFSCCLV 
                   
               
               
                   
                 KSIRSGYEVM 
                   
               
               
                   
                 ATGGCGGTGGAAGGAGGAATGAAGTGTGTCAAGTTTTTGCTCTACGTTCTCCTGCTG 
                 28 
               
               
                   
                 GCCTTCTGCGCCTGTGCAGTGGGATTGATCGCCATTGGTGTAGCGGTTCAGGTTGTC 
                   
               
               
                   
                 TTGAAGCAGGCCATTACCCATGAGACTACTGCTGGCTCGCTGTTGCCTGTGGTCATC 
                   
               
               
                   
                 ATTGCAGTGGGTGCCTTCCTCTTCCTGGTGGCCTTTGTGGGCTGCTGTGGGGCCTGC 
                   
               
               
                   
                 AAGGAGAACTACTGTCTCATGATTACATTTGCCATCTTCCTGTCTCTTATCATGCTT 
                   
               
               
                   
                 GTGGAGGTGGCTGTGGCCATTGCTGGCTATGTGTTTAGAGACCAGGTGAAGTCAGAG 
                   
               
               
                   
                 TTTAATAAAAGCTTCCAGCAGCAGATGCAGAATTACCTTAAAGACAACAAAACAGCC 
                   
               
               
                   
                 ACTATTTTGGACAAATTGCAGAAAGAAAATAACTGCTGTGGAGCTTCTAACTACACA 
                   
               
               
                   
                 GACTGGGAAAACATCCCCGGCATGGCCAAGGACAGAGTCCCCGATTCTTGCTGCATC 
                   
               
               
                   
                 AACATAACTGTGGGCTGTGGGAATGATTTCAAGGAATCCACTATCCATACCCAGGGC 
                   
               
               
                   
                 TGCGTGGAGACTATAGCAATATGGCTAAGGAAGAACATACTGCTGGTGGCTGCAGCG 
                   
               
               
                   
                 GCCCTGGGCATTGCTTTTGTGGAGGTCTTGGGAATTATCTTCTCCTGCTGTCTGGTG 
                   
               
               
                   
                 AAGAGTATTCGAAGTGGCTATGAAGTAATGTAG 
                   
               
               
                   
               
               
                 CD63 
                 MAVEGGMKCVKFLLYVLLLAFCACAVGLIAIGVAVQVVLKQAITHETTAGSLLPVVI 
                 57 
               
               
                 (amino 
                 IAVGAFLFLVAFVGCCGACKENYCLMITFAIFLSLIMLVEVAVAIAGYVFRDQVKSE 
                   
               
               
                 acids 
                 FNKSFQQQMQNYLKDNKTATILDKLQKENNCCGASNYTDWENIPGMAKDRVPDSCC 
                   
               
               
                 1 to 
                 ATGGCGGTGGAAGGAGGAATGAAGTGTGTCAAGTTTTTGCTCTACGTTCTCCTGCTG 
                 58 
               
               
                 170) 
                 GCCTTCTGCGCCTGTGCAGTGGGATTGATCGCCATTGGTGTAGCGGTTCAGGTTGTC 
                   
               
               
                   
                 TTGAAGCAGGCCATTACCCATGAGACTACTGCTGGCTCGCTGTTGCCTGTGGTCATC 
                   
               
               
                   
                 ATTGCAGTGGGTGCCTTCCTCTTCCTGGTGGCCTTTGTGGGCTGCTGTGGGGCCTGC 
                   
               
               
                   
                 AAGGAGAACTACTGTCTCATGATTACATTTGCCATCTTCCTGTCTCTTATCATGCTT 
                   
               
               
                   
                 GTGGAGGTGGCTGTGGCCATTGCTGGCTATGTGTTTAGAGACCAGGTGAAGTCAGAG 
                   
               
               
                   
                 TTTAATAAAAGCTTCCAGCAGCAGATGCAGAATTACCTTAAAGACAACAAAACAGCC 
                   
               
               
                   
                 ACTATTTTGGACAAATTGCAGAAAGAAAATAACTGCTGTGGAGCTTCTAACTACACA 
                   
               
               
                   
                 GACTGGGAAAACATCCCCGGCATGGCCAAGGACAGAGTCCCCGATTCTTGCTGC 
                   
               
               
                   
               
               
                 CD63 
                 INITVGCGNDFKESTIHTQGCVETIAIWLRKNILLVAAAALGIAFVEVLGIIFSCCL 
                 59 
               
               
                 (amino 
                 VKSIRSGYEVM 
                   
               
               
                 acids 
                 ATCAACATAACTGTGGGCTGTGGGAATGATTTCAAGGAATCCACTATCCATACCCAG 
                 60 
               
               
                 171 to 
                 GGCTGCGTGGAGACTATAGCAATATGGCTAAGGAAGAACATACTGCTGGTGGCTGCA 
                   
               
               
                 238) 
                 GCGGCCCTGGGCATTGCTTTTGTGGAGGTCTTGGGAATTATCTTCTCCTGCTGTCTG 
                   
               
               
                   
                 GTGAAGAGTATTCGAAGTGGCTATGAAGTAATGTAG 
                   
               
               
                   
               
               
                 Peptide 
                 GGGGS 
                 29 
               
               
                 linker 3 
                 GGAGGAGGAGGAAGC 
                 30 
               
               
                   
               
               
                 CD63- 
                 MAVEGGMKCVKFLLYVLLLAFCACAVGLIAIGVAVQVVLKQAITHETTAGSLLPVVI 
                 31 
               
               
                 IL-2 
                 IAVGAFLFLVAFVGCCGACKENYCLMITFAIFLSLIMLVEVAVAIAGYVFRDQVKSE 
                   
               
               
                   
                 FNKSFQQQMQNYLKDNKTATILDKLQKENNCCGASNYTDWENIPGMAKDRVPDSCCG 
                   
               
               
                   
                 GGGSAPTSSSTSSSTAEAQQQQQQQQQQQQHLEQLLMDLQELLSRMENYRNLKLPRM 
                   
               
               
                   
                 LTFKFYLPKQATELKDLQCLEDELGPLRHVLDLTQSKSFQLEDAENFISNIRVTVVK 
                   
               
               
                   
                 LKGSDNTFECQFDDESATVVDFLRRWIAFCQSIISTSPQGGGGSINITVGCGNDFKE 
                   
               
               
                   
                 STIHTQGCVETIAIWLRKNILLVAAAALGIAFVEVLGIIFSCCLVKSIRSGYEVM 
                   
               
               
                   
                 ATGGCGGTGGAAGGAGGAATGAAGTGTGTCAAGTTTTTGCTCTACGTTCTCCTGCTG 
                 32 
               
               
                   
                 GCCTTCTGCGCCTGTGCAGTGGGATTGATCGCCATTGGTGTAGCGGTTCAGGTTGTC 
                   
               
               
                   
                 TTGAAGCAGGCCATTACCCATGAGACTACTGCTGGCTCGCTGTTGCCTGTGGTCATC 
                   
               
               
                   
                 ATTGCAGTGGGTGCCTTCCTCTTCCTGGTGGCCTTTGTGGGCTGCTGTGGGGCCTGC 
                   
               
               
                   
                 AAGGAGAACTACTGTCTCATGATTACATTTGCCATCTTCCTGTCTCTTATCATGCTT 
                   
               
               
                   
                 GTGGAGGTGGCTGTGGCCATTGCTGGCTATGTGTTTAGAGACCAGGTGAAGTCAGAG 
                   
               
               
                   
                 TTTAATAAAAGCTTCCAGCAGCAGATGCAGAATTACCTTAAAGACAACAAAACAGCC 
                   
               
               
                   
                 ACTATTTTGGACAAATTGCAGAAAGAAAATAACTGCTGTGGAGCTTCTAACTACACA 
                   
               
               
                   
                 GACTGGGAAAACATCCCCGGCATGGCCAAGGACAGAGTCCCCGATTCTTGCTGCGGA 
                   
               
               
                   
                 GGAGGAGGAAGCGCACCCACTTCAAGCTCCACTTCAAGCTCTACAGCGGAAGCACAG 
                   
               
               
                   
                 CAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCACCTGGAGCAGCTGTTGATGGAC 
                   
               
               
                   
                 CTACAGGAGCTCCTGAGCAGGATGGAGAATTACAGGAACCTGAAACTCCCCAGGATG 
                   
               
               
                   
                 CTCACCTTCAAATTTTACTTGCCCAAGCAGGCCACAGAATTGAAAGATCTTCAGTGC 
                   
               
               
                   
                 CTAGAAGATGAACTTGGACCTCTGCGGCATGTTCTGGATTTGACTCAAAGCAAAAGC 
                   
               
               
                   
                 TTTCAATTGGAAGATGCTGAGAATTTCATCAGCAATATCAGAGTAACTGTTGTAAAA 
                   
               
               
                   
                 CTAAAGGGCTCTGACAACACATTTGAGTGCCAATTCGATGATGAGTCAGCAACTGTG 
                   
               
               
                   
                 GTGGACTTTCTGAGGAGATGGATAGCCTTCTGTCAAAGCATCATCTCAACAAGCCCT 
                   
               
               
                   
                 CAAGGAGGAGGAGGAAGCATCAACATAACTGTGGGCTGTGGGAATGATTTCAAGGAA 
                   
               
               
                   
                 TCCACTATCCATACCCAGGGCTGCGTGGAGACTATAGCAATATGGCTAAGGAAGAAC 
                   
               
               
                   
                 ATACTGCTGGTGGCTGCAGCGGCCCTGGGCATTGCTTTTGTGGAGGTCTTGGGAATT 
                   
               
               
                   
                 ATCTTCTCCTGCTGTCTGGTGAAGAGTATTCGAAGTGGCTATGAAGTAATGTAG 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
             
               
                 TABLE 4 
               
               
                   
               
               
                   
                   
                 SEQ 
               
               
                   
                   
                 ID 
               
               
                   
                 Sequence 
                 NO: 
               
               
                   
               
             
            
               
                 Signal 
                 
                   MALQIPSLLLSAAVVVLMVLSSPGTEG 
                 
                 33 
               
               
                 peptide 
                 
                   ATGGCTCTGCAGATCCCCAGCCTCCTCCTCTCGGCTGCTGTGGTGGTGCTGATGGTG 
                 
                 34 
               
               
                 of MHC 
                 
                   CTGAGCAGCCCAGGGACTGAGGGC 
                 
                   
               
               
                 class IIβ 
                   
                   
               
               
                 chain 
                   
                   
               
               
                   
               
               
                 OVA 
                 ISQAVHAAHAEINEAGR 
                 35 
               
               
                 peptide 2 
                 ATATCTCAAGCTGTCCATGCAGCACATGCAGAAATCAATGAAGCAGGCAGA 
                 36 
               
               
                 (for MHC 
                   
                   
               
               
                 class II 
                   
                   
               
               
                 molecule) 
                   
                   
               
               
                   
               
               
                 MHC 
                 GDSERHFVYQFMGECYFTNGTQRIRYVTRYIYNREEYVRYDSDVGEHRAVTELGRPD 
                 37 
               
               
                 class IIβ 
                 AEYWNSQPEILERTRAELDTVCRHNYEGPETHTSLRRLEQPNVVISLSRTEALNHHN 
                   
               
               
                 chain 
                 TLVCSVTDFYPAKIKVRWFRNGQEETVGVSSTQLIRNGDWTFQVLVMLEMTPRRGEV 
                   
               
               
                 (from  
                 YTCHVEHPSLKSPITVEWRAQSESAWSKMLSGIGGCVLGVIFLGLGLFIRHRSQKGP 
                   
               
               
                 which 
                 RGPPPAGLLQ 
                   
               
               
                 signal 
                 GGAGACTCCGAAAGGCATTTCGTGTACCAGTTCATGGGCGAGTGCTACTTCACCAAC 
                 38 
               
               
                 peptide 
                 GGGACGCAGCGCATACGATATGTGACCAGATACATCTACAACCGGGAGGAGTACGTG 
                   
               
               
                 is 
                 CGCTACGACAGCGACGTGGGCGAGCACCGCGCGGTGACCGAGCTGGGGCGGCCAGAC 
                   
               
               
                 removed) 
                 GCCGAGTACTGGAACAGCCAGCCGGAGATCCTGGAGCGAACGCGGGCCGAGCTGGAC 
                   
               
               
                   
                 ACGGTGTGCAGACACAACTACGAGGGGCCGGAGACCCACACCTCCCTGCGGCGGCTT 
                   
               
               
                   
                 GAACAGCCCAATGTCGTCATCTCCCTGTCCAGGACAGAGGCCCTCAACCACCACAAC 
                   
               
               
                   
                 ACTCTGGTCTGCTCAGTGACAGATTTCTACCCAGCCAAGATCAAAGTGCGCTGGTTC 
                   
               
               
                   
                 CGGAATGGCCAGGAGGAGACGGTGGGGGTCTCATCCACACAGCTTATTAGGAATGGG 
                   
               
               
                   
                 GACTGGACCTTCCAGGTCCTGGTCATGCTGGAGATGACCCCTCGGCGGGGAGAGGTC 
                   
               
               
                   
                 TACACCTGTCACGTGGAGCATCCCAGCCTGAAGAGCCCCATCACTGTGGAGTGGAGG 
                   
               
               
                   
                 GCACAGTCTGAGTCTGCCTGGAGCAAGATGTTGAGCGGCATCGGGGGCTGCGTGCTT 
                   
               
               
                   
                 GGGGTGATCTTCCTCGGGCTTGGCCTTTTCATCCGTCACAGGAGTCAGAAAGGACCT 
                   
               
               
                   
                 CGAGGCCCTCCTCCAGCAGGGCTCCTGCAG 
                   
               
               
                   
               
               
                 Peptide 
                 GGGGSGGGGSG 
                 39 
               
               
                 linker 4 
                 GGAGGAGGAGGAAGCGGAGGAGGAGGAAGCGGA 
                 40 
               
               
                   
               
               
                 sc- 
                   MALQIPSLLLSAAVVVLMVLSSPGTEG ISQAVHAAHAEINEAGRGGGGSGGGGSGGD 
                 41 
               
               
                 Dimer 
                 SERHFVYQFMGECYFTNGTQRIRYVTRYIYNREEYVRYDSDVGEHRAVTELGRPDAE 
                   
               
               
                 (OVA 
                 YWNSQPEILERTRAELDTVCRHNYEGPETHTSLRRLEQPNVVISLSRTEALNHHNTL 
                   
               
               
                 pep- 
                 VCSVTDFYPAKIKVRWFRNGQEETVGVSSTQLIRNGDWTFQVLVMLEMTPRRGEVYT 
                   
               
               
                 tide 2 + 
                 CHVEHPSLKSPITVEWRAQSESAWSKMLSGIGGCVLGVIFLGLGLFIRHRSQKGPRG 
                   
               
               
                 peptide 
                 PPPAGLLQ 
                   
               
               
                 linker  
                 
                   ATGGCTCTGCAGATCCCCAGCCTCCTCCTCTCGGCTGCTGTGGTGGTGCTGATGGTG 
                 
                 42 
               
               
                 4 + 
                   CTGAGCAGCCCAGGGACTGAGGGC ATATCTCAAGCTGTCCATGCAGCACATGCAGAA 
                   
               
               
                 MHC 
                 ATCAATGAAGCAGGCAGAGGAGGAGGAGGAAGCGGAGGAGGAGGAAGCGGAGGAGAC 
                   
               
               
                 class IIβ 
                 TCCGAAAGGCATTTCGTGTACCAGTTCATGGGCGAGTGCTACTTCACCAACGGGACG 
                   
               
               
                 chain  
                 CAGCGCATACGATATGTGACCAGATACATCTACAACCGGGAGGAGTACGTGCGCTAC 
                   
               
               
                 (from  
                 GACAGCGACGTGGGCGAGCACCGCGCGGTGACCGAGCTGGGGCGGCCAGACGCCGAG 
                   
               
               
                 which 
                 TACTGGAACAGCCAGCCGGAGATCCTGGAGCGAACGCGGGCCGAGCTGGACACGGTG 
                   
               
               
                 signal  
                 TGCAGACACAACTACGAGGGGCCGGAGACCCACACCTCCCTGCGGCGGCTTGAACAG 
                   
               
               
                 peptide 
                 CCCAATGTCGTCATCTCCCTGTCCAGGACAGAGGCCCTCAACCACCACAACACTCTG 
                   
               
               
                 is  
                 GTCTGCTCAGTGACAGATTTCTACCCAGCCAAGATCAAAGTGCGCTGGTTCCGGAAT 
                   
               
               
                 removed)) 
                 GGCCAGGAGGAGACGGTGGGGGTCTCATCCACACAGCTTATTAGGAATGGGGACTGG 
                   
               
               
                   
                 ACCTTCCAGGTCCTGGTCATGCTGGAGATGACCCCTCGGCGGGGAGAGGTCTACACC 
                   
               
               
                   
                 TGTCACGTGGAGCATCCCAGCCTGAAGAGCCCCATCACTGTGGAGTGGAGGGCACAG 
                   
               
               
                   
                 TCTGAGTCTGCCTGGAGCAAGATGTTGAGCGGCATCGGGGGCTGCGTGCTTGGGGTG 
                   
               
               
                   
                 ATCTTCCTCGGGCTTGGCCTTTTCATCCGTCACAGGAGTCAGAAAGGACCTCGAGGC 
                   
               
               
                   
                 CCTCCTCCAGCAGGGCTCCTGCAG 
                   
               
               
                   
               
               
                 sc-    
                   MALQIPSLLLSAAVVVLMVLSSPGTEG ISQAVHAAHAEINEAGRGGGGSGGGGSGGD 
                 43 
               
               
                 Dimer- 
                 SERHFVYQFMGECYFTNGTQRIRYVTRYIYNREEYVRYDSDVGEHRAVTELGRPDAE 
                   
               
               
                 CD81 
                 YWNSQPEILERTRAELDTVCRHNYEGPETHTSLRRLEQPNVVISLSRTEALNHHNTL 
                   
               
               
                   
                 VCSVTDFYPAKIKVRWFRNGQEETVGVSSTQLIRNGDWTFQVLVMLEMTPRRGEVYT 
                   
               
               
                   
                 CHVEHPSLKSPITVEWRAQSESAWSKMLSGIGGCVLGVIFLGLGLFIRHKSQKGPRG 
                   
               
               
                   
                 PPPAGLLQMGVEGCTKCIKYLLFVFNFVFWLAGGVILGVALWLRHDPQTTSLLYLEL 
                   
               
               
                   
                 GNKPAPNTFYVGIYILIAVGAVMMFVGFLGCYGAIQESQCLLGTFFTCLVILFACEV 
                   
               
               
                   
                 AAGIWGFVNKDQIAKDVKQFYDQALQQAVMDDDANNAKAVVKTFHETLNCCGSNALT 
                   
               
               
                   
                 TLTTTILRNSLCPSGGNILTPLLQQDCHQKIDELFSGKLYLIGIAAIVVAVIMIFEM 
                   
               
               
                   
                 ILSMVLCCGIRNSSVY 
                   
               
               
                     
                 
                   ATGGCTCTGCAGATCCCCAGCCTCCTCCTCTCGGCTGCTGTGGTGGTGCTGATGGTG 
                 
                 44 
               
               
                   
                   CTGAGCAGCCCAGGGACTGAGGGC ATATCTCAAGCTGTCCATGCAGCACATGCAGAA 
                   
               
               
                   
                 ATCAATGAAGCAGGCAGAGGAGGAGGAGGAAGCGGAGGAGGAGGAAGCGGAGGAGAC 
                   
               
               
                   
                 TCCGAAAGGCATTTCGTGTACCAGTTCATGGGCGAGTGCTACTTCACCAACGGGACG 
                   
               
               
                   
                 CAGCGCATACGATATGTGACCAGATACATCTACAACCGGGAGGAGTACGTGCGCTAC 
                   
               
               
                   
                 GACAGCGACGTGGGCGAGCACCGCGCGGTGACCGAGCTGGGGCGGCCAGACGCCGAG 
                   
               
               
                   
                 TACTGGAACAGCCAGCCGGAGATCCTGGAGCGAACGCGGGCCGAGCTGGACACGGTG 
                   
               
               
                   
                 TGCAGACACAACTACGAGGGGCCGGAGACCCACACCTCCCTGCGGCGGCTTGAACAG 
                   
               
               
                   
                 CCCAATGTCGTCATCTCCCTGTCCAGGACAGAGGCCCTCAACCACCACAACACTCTG 
                   
               
               
                   
                 GTCTGCTCAGTGACAGATTTCTACCCAGCCAAGATCAAAGTGCGCTGGTTCCGGAAT 
                   
               
               
                   
                 GGCCAGGAGGAGACGGTGGGGGTCTCATCCACACAGCTTATTAGGAATGGGGACTGG 
                   
               
               
                   
                 ACCTTCCAGGTCCTGGTCATGCTGGAGATGACCCCTCGGCGGGGAGAGGTCTACACC 
                   
               
               
                   
                 TGTCACGTGGAGCATCCCAGCCTGAAGAGCCCCATCACTGTGGAGTGGAGGGCACAG 
                   
               
               
                   
                 TCTGAGTCTGCCTGGAGCAAGATGTTGAGCGGCATCGGGGGCTGCGTGCTTGGGGTG 
                   
               
               
                   
                 ATCTTCCTCGGGCTTGGCCTTTTCATCCGTCACAGGAGTCAGAAAGGACCTCGAGGC 
                   
               
               
                   
                 CCTCCTCCAGCAGGGCTCCTGCAGATGGGGGTGGAGGGCTGCACCAAATGCATCAAA 
                   
               
               
                   
                 TACCTGCTCTTCGTCTTCAATTTCGTCTTCTGGCTGGCTGGAGGCGTGATCCTAGGT 
                   
               
               
                   
                 GTAGCTCTGTGGTTGCGTCATGATCCACAGACCACCAGCCTGCTGTACCTGGAACTG 
                   
               
               
                   
                 GGAAACAAACCGGCACCCAACACCTTCTACGTGGGCATCTACATTCTCATTGCTGTG 
                   
               
               
                   
                 GGAGCTGTGATGATGTTTGTAGGCTTCCTGGGGTGCTATGGGGCCATCCAGGAGTCC 
                   
               
               
                   
                 CAGTGTCTGCTGGGGACGTTCTTCACCTGCCTTGTGATCCTGTTTGCCTGTGAGGTG 
                   
               
               
                   
                 GCTGCAGGCATCTGGGGCTTCGTAAACAAAGACCAGATCGCCAAGGATGTGAAGCAG 
                   
               
               
                   
                 TTCTATGACCAGGCCCTTCAGCAAGCTGTGATGGATGATGATGCCAACAATGCCAAG 
                   
               
               
                   
                 GCTGTGGTGAAGACTTTCCATGAGACGCTCAACTGTTGTGGCTCCAACGCACTGACC 
                   
               
               
                   
                 ACACTGACTACCACCATACTGAGGAACAGCCTGTGTCCCTCAGGCGGCAACATACTC 
                   
               
               
                   
                 ACCCCCTTACTGCAGCAAGATTGTCATCAGAAAATCGATGAGCTCTTCTCTGGGAAG 
                   
               
               
                   
                 CTGTACCTCATTGGAATTGCAGCCATTGTGGTAGCTGTCATTATGATCTTTGAGATG 
                   
               
               
                   
                 ATTCTGAGCATGGTGCTGTGCTGTGGCATCCGGAACAGCTCCGTGTACTGA 
                   
               
               
                   
               
               
                 MHC  
                   MPRSRALILGVLALTTMLSLCGG EDDIEADHVGTYGISVYQSPGDIGQYTFEFDGDE 
                 45 
               
               
                 class IIα 
                 LFYVDLDKKETVWMLPEFGQLASFDPQGGLQNIAVVKHNLGVLTKRSNSTPATNEAP 
                   
               
               
                 chain 
                 QATVFPKSPVLLGQPNTLICFVDNIFPPVINITWLRNSKSVADGVYETSFFVNRDYS 
                   
               
               
                   
                 FHKLSYLTFIPSDDDIYDCKVEHWGLEEPVLKHWEPEIPAPMSELTETVVCALGLSV 
                   
               
               
                   
                 GLVGIVVGTIFIIQGLRSGGTSRHPGPL 
                   
               
               
                   
                 
                   ATGCCGCGCAGCAGAGCTCTGATTCTGGGGGTCCTCGCCCTGACCACCATGCTCAGC 
                 
                 46 
               
               
                   
                   CTCTGTGGAGGT GAAGACGACATTGAGGCCGACCACGTAGGCACCTATGGTATAAGT 
                   
               
               
                   
                 GTATATCAGTCTCCTGGAGACATTGGCCAGTACACATTTGAATTTGATGGTGATGAG 
                   
               
               
                   
                 TTGTTCTATGTGGACTTGGATAAGAAGGAGACTGTCTGGATGCTTCCTGAGTTTGGC 
                   
               
               
                   
                 CAATTGGCAAGCTTTGACCCCCAAGGTGGACTGCAAAACATAGCTGTAGTAAAACAC 
                   
               
               
                   
                 AACTTGGGAGTCTTGACTAAGAGGTCAAATTCCACCCCAGCTACCAATGAGGCTCCT 
                   
               
               
                   
                 CAAGCGACTGTGTTCCCCAAGTCCCCTGTGCTGCTGGGTCAGCCCAACACCCTCATC 
                   
               
               
                   
                 TGCTTTGTGGACAACATCTTCCCTCCTGTGATCAACATCACATGGCTCAGAAATAGC 
                   
               
               
                   
                 AAGTCAGTCGCAGACGGTGTTTATGAGACCAGCTTCTTCGTCAACCGTGACTATTCC 
                   
               
               
                   
                 TTCCACAAGCTGTCTTATCTCACCTTCATCCCTTCTGACGATGACATTTATGACTGC 
                   
               
               
                   
                 AAGGTGGAACACTGGGGCCTGGAGGAGCCGGTTCTGAAACACTGGGAACCTGAGATT 
                   
               
               
                   
                 CCAGCCCCCATGTCAGAGCTGACAGAGACTGTGGTCTGTGCCCTGGGGTTGTCTGTG 
                   
               
               
                   
                 GGCCTTGTGGGCATCGTGGTGGGCACCATCTTCATCATTCAAGGCCTGCGATCAGGT 
                   
               
               
                   
                 GGCACCTCCAGACACCCAGGGCCTTTATGA 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
             
               
                 TABLE 5 
               
               
                   
               
               
                   
                   
                 SEQ 
               
               
                   
                   
                 ID  
               
               
                   
                 Sequence 
                 NO: 
               
               
                   
               
             
            
               
                 TGF-β1 
                   MPPSGLRLLPLLLPLPWLLVLTPGRPAAG LSTSKTIDMELVKRKRIEAIRGQILSKL 
                 47 
               
               
                   
                 RLASPPSQGEVPPGPLPEAVLALYNSTRDRVAGESADPEPEPEADYYAKEVTRVLMV 
                   
               
               
                   
                 DRNNAIYEKTKDISHSIYMFFNTSDIREAVPEPPLLSRAELRLQRLKSSVEQHVELY 
                   
               
               
                   
                 QKYSNNSWRYLGNRLLTPTDTPEWLSFDVTGVVRQWLNQGDGIQGFRFSAHSSSDSK 
                   
               
               
                   
                 DNKLHVEINGISPKRRGDLGTIHDMNRPFLLLMATPLERAQHLHSSRHRRALDTNYC 
                   
               
               
                   
                 FSSTEKNCCVRQLYIDFRKDLGWKWIHEPKGYHANFCLGPCPYIWSLDTQYSKVLAL 
                   
               
               
                   
                 YNQHNPGASASPCCVPQALEPLPIVYYVGRKPKVEQLSNMIVRSCKCS 
                   
               
               
                   
                 
                   ATGCCGCCCTCGGGGCTGCGGCTACTGCCGCTTCTGCTCCCACTCCCGTGGCTTCTA 
                 
                 48 
               
               
                   
                   GTGCTGACGCCCGGGAGGCCAGCCGCGGGA CTCTCCACCTCTAAGACCATCGACATG 
                   
               
               
                   
                 GAGCTGGTGAAACGGAAGCGCATCGAAGCCATCCGTGGCCAGATCCTGTCCAAACTA 
                   
               
               
                   
                 AGGCTCGCCAGTCCCCCAAGCCAGGGGGAGGTACCGCCCGGCCCGCTGCCCGAGGCG 
                   
               
               
                   
                 GTGCTCGCTTTGTACAACAGCACCCGCGACCGGGTGGCAGGCGAGAGCGCCGACCCA 
                   
               
               
                   
                 GAGCCGGAGCCCGAAGCGGACTACTATGCTAAAGAGGTCACCCGCGTGCTAATGGTG 
                   
               
               
                   
                 GACCGCAACAACGCCATCTATGAGAAAACCAAAGACATCTCACACAGTATATATATG 
                   
               
               
                   
                 TTCTTCAATACGTCAGACATTCGGGAAGCAGTGCCCGAACCCCCATTGCTGTCCCGT 
                   
               
               
                   
                 GCAGAGCTGCGCTTGCAGAGATTAAAATCAAGTGTGGAGCAACATGTGGAACTCTAC 
                   
               
               
                   
                 CAGAAATATAGCAACAATTCCTGGCGTTACCTTGGTAACCGGCTGCTGACCCCCACT 
                   
               
               
                   
                 GATACGCCTGAGTGGCTGTCTTTTGACGTCACTGGAGTTGTACGGCAGTGGCTGAAC 
                   
               
               
                   
                 CAAGGAGACGGAATACAGGGCTTTCGATTCAGCGCTCACTCTTCTTCTGACAGCAAA 
                   
               
               
                   
                 GATAACAAACTCCACGTGGAAATCAACGGGATCAGCCCCAAACGTCGGGGCGACCTG 
                   
               
               
                   
                 GGCACCATCCATGACATGAACCGGCCCTTCCTGCTCCTCATGGCCACCCCCCTGGAA 
                   
               
               
                   
                 AGGGCCCAGCACCTGCACAGCTCACGGCACCGGAGAGCCCTGGATACCAACTATTGC 
                   
               
               
                   
                 TTCAGCTCCACAGAGAAGAACTGCTGTGTGCGGCAGCTGTACATTGACTTTAGGAAG 
                   
               
               
                   
                 GACCTGGGTTGGAAGTGGATCCACGAGCCCAAGGGCTACCATGCCAACTTCTGTCTG 
                   
               
               
                   
                 GGACCCTGCCCCTATATTTGGAGCCTGGACACACAGTACAGCAAGGTCCTTGCCCTC 
                   
               
               
                   
                 TACAACCAACACAACCCGGGCGCTTCGGCGTCACCGTGCTGCGTGCCGCAGGCTTTG 
                   
               
               
                   
                 GAGCCACTGCCCATCGTCTACTACGTGGGTCGCAAGCCCAAGGTGGAGCAGTTGTCC 
                   
               
               
                   
                 AACATGATTGTGCGCTCCTGCAAGTGCAGCTGA 
                   
               
               
                   
               
               
                 MFG-E8 
                 ASGDFCDSSLCLNGGTCLTGQDNDIYCLCPEGFTGLVCNETERGPCSPNPCYNDAKC 
                 49 
               
               
                 (from  
                 LVTLDTQRGEIFTEYICQCPVGYSGIHCETETNYYNLDGEYMFTTAVPNTAVPTPAP 
                   
               
               
                 which 
                 TPDLSNNLASRCSTQLGMEGGAIADSQISASSVYMGFMGLQRWGPELARLYRTGIVN 
                   
               
               
                 signal  
                 AWTASNYDSKPWIQVNLLRKMRVSGVMTQGASRAGRAEYLKTFKVAYSLDGRKFEFI 
                   
               
               
                 peptide 
                 QDESGGDKEFLGNLDNNSLKVNMFNPTLEAQYIKLYPVSCHRGCTLRFELLGCELHG 
                   
               
               
                 is  
                 CSEPLGLKNNTIPDSQMSASSSYKTWNLRAFGWYPHLGRLDNQGKINAWTAQSNSAK 
                   
               
               
                 removed) 
                 EWLQVDLGTQRQVTGIITQGARDFGHIQYVASYKVAHSDDGVQWTVYEEQGSSKVFQ 
                   
               
               
                   
                 GNLDNNSHKKNIFEKPFMARYVRVLPVSWHNRITLRLELLGC 
                   
               
               
                   
                 GCGTCTGGTGACTTCTGTGACTCCAGCCTGTGCCTGAACGGTGGCACCTGCTTGACG 
                 50 
               
               
                   
                 GGCCAAGACAATGACATCTACTGCCTCTGCCCTGAAGGCTTCACAGGCCTTGTGTGC 
                   
               
               
                   
                 AATGAGACTGAGAGAGGACCATGCTCCCCAAACCCTTGCTACAATGATGCCAAATGT 
                   
               
               
                   
                 CTGGTGACTTTGGACACACAGCGTGGGGAAATCTTCACCGAATACATCTGCCAGTGC 
                   
               
               
                   
                 CCTGTGGGCTACTCGGGCATCCACTGTGAAACCGAGACCAACTACTACAACCTGGAT 
                   
               
               
                   
                 GGAGAATACATGTTCACCACAGCCGTCCCCAATACTGCCGTCCCCACCCCGGCCCCC 
                   
               
               
                   
                 ACCCCCGATCTTTCCAACAACCTAGCCTCCCGTTGTTCTACACAGCTGGGCATGGAA 
                   
               
               
                   
                 GGGGGCGCCATTGCTGATTCACAGATTTCCGCCTCGTCTGTGTATATGGGTTTCATG 
                   
               
               
                   
                 GGCTTGCAGCGCTGGGGCCCGGAGCTGGCTCGTCTGTACCGCACAGGGATCGTCAAT 
                   
               
               
                   
                 GCCTGGACAGCCAGCAACTATGATAGCAAGCCCTGGATCCAGGTGAACCTTCTGCGG 
                   
               
               
                   
                 AAGATGCGGGTATCAGGTGTGATGACGCAGGGTGCCAGCCGTGCCGGGAGGGCGGAG 
                   
               
               
                   
                 TACCTGAAGACCTTCAAGGTGGCTTACAGCCTCGACGGACGCAAGTTTGAGTTCATC 
                   
               
               
                   
                 CAGGATGAAAGCGGTGGAGACAAGGAGTTTTTGGGTAACCTGGACAACAACAGCCTG 
                   
               
               
                   
                 AAGGTTAACATGTTCAACCCGACTCTGGAGGCACAGTACATAAAGCTGTACCCTGTT 
                   
               
               
                   
                 TCGTGCCACCGCGGCTGCACCCTCCGCTTCGAGCTCCTGGGCTGTGAGTTGCACGGA 
                   
               
               
                   
                 TGTTCTGAGCCCCTGGGCCTGAAGAATAACACAATTCCTGACAGCCAGATGTCAGCC 
                   
               
               
                   
                 TCCAGCAGCTACAAGACATGGAACCTGCGTGCTTTTGGCTGGTACCCCCACTTGGGA 
                   
               
               
                   
                 AGGCTGGATAATCAGGGCAAGATCAATGCCTGGACGGCTCAGAGCAACAGTGCCAAG 
                   
               
               
                   
                 GAATGGCTGCAGGTTGACCTGGGCACTCAGAGGCAAGTGACAGGAATCATCACCCAG 
                   
               
               
                   
                 GGGGCCCGTGACTTTGGCCACATCCAGTATGTGGCGTCCTACAAGGTAGCCCACAGT 
                   
               
               
                   
                 GATGATGGTGTGCAGTGGACTGTATATGAGGAGCAAGGAAGCAGCAAGGTCTTCCAG 
                   
               
               
                   
                 GGCAACTTGGACAACAACTCCCACAAGAAGAACATCTTCGAGAAACCCTTCATGGCT 
                   
               
               
                   
                 CGCTACGTGCGTGTCCTTCCAGTGTCCTGGCATAACCGCATCACCCTGCGCCTGGAG 
                   
               
               
                   
                 CTGCTGGGCTGTTAA 
                   
               
               
                   
               
               
                 TGF-β1- 
                   MPPSGLRLLPLLLPLPWLLVLTPGRPAAG LSTSKTIDMELVKRKRIEAIRGQILSKL 
                 51 
               
               
                 MFG-E8 
                 RLASPPSQGEVPPGPLPEAVLALYNSTRDRVAGESADPEPEPEADYYAKEVTRVLMV 
                   
               
               
                 (TGF-β1 + 
                 DRNNAIYEKTKDISHSIYMFFNTSDIREAVPEPPLLSRAELRLQRLKSSVEQHVELY 
                   
               
               
                 peptide  
                 QKYSNNSWRYLGNRLLTPTDTPEWLSFDVTGVVRQWLNQGDGIQGFRFSAHSSSDSK 
                   
               
               
                 linker 
                 DNKLHVEINGISPKRRGDLGTIHDMNRPFLLLMATPLERAQHLHSSRHRRALDTNYC 
                   
               
               
                 3 +  
                 FSSTEKNCCVRQLYIDFRKDLGWKWIHEPKGYHANFCLGPCPYIWSLDTQYSKVLAL 
                   
               
               
                 MFG-E8 
                 YNQHNPGASASPCCVPQALEPLPIVYYVGRKPKVEQLSNMIVRSCKCSGGGGSASGD 
                   
               
               
                 (from  
                 FCDSSLCLNGGTCLTGQDNDIYCLCPEGFTGLVCNETERGPCSPNPCYNDAKCLVTL 
                   
               
               
                 which 
                 DTQRGEIFTEYICQCPVGYSGIHCETETNYYNLDGEYMFTTAVPNTAVPTPAPTPDL 
                   
               
               
                 signal  
                 SNNLASRCSTQLGMEGGAIADSQISASSVYMGFMGLQRWGPELARLYRTGIVNAWTA 
                   
               
               
                 peptide 
                 SNYDSKPWIQVNLLRKMRVSGVMTQGASRAGRAEYLKTFKVAYSLDGRKFEFIQDES 
                   
               
               
                 is 
                 GGDKEFLGNLDNNSLKVNMFNPTLEAQYIKLYPVSCHRGCTLRFELLGCELHGCSEP 
                   
               
               
                 removed)) 
                 LGLKNNTIPDSQMSASSSYKTWNLRAFGWYPHLGRLDNQGKINAWTAQSNSAKEWLQ 
                   
               
               
                   
                 VDLGTQRQVTGIITQGARDFGHIQYVASYKVAHSDDGVQWTVYEEQGSSKVFQGNLD 
                   
               
               
                   
                 NNSHKKNIFEKPFMARYVRVLPVSWHNRITLRLELLGC 
                   
               
               
                   
                 
                   ATGCCGCCCTCGGGGCTGCGGCTACTGCCGCTTCTGCTCCCACTCCCGTGGCTTCTA 
                 
                 52 
               
               
                   
                   GTGCTGACGCCCGGGAGGCCAGCCGCGGGA CTCTCCACCTCTAAGACCATCGACATG 
                   
               
               
                   
                 GAGCTGGTGAAACGGAAGCGCATCGAAGCCATCCGTGGCCAGATCCTGTCCAAACTA 
                   
               
               
                   
                 AGGCTCGCCAGTCCCCCAAGCCAGGGGGAGGTACCGCCCGGCCCGCTGCCCGAGGCG 
                   
               
               
                   
                 GTGCTCGCTTTGTACAACAGCACCCGCGACCGGGTGGCAGGCGAGAGCGCCGACCCA 
                   
               
               
                   
                 GAGCCGGAGCCCGAAGCGGACTACTATGCTAAAGAGGTCACCCGCGTGCTAATGGTG 
                   
               
               
                   
                 GACCGCAACAACGCCATCTATGAGAAAACCAAAGACATCTCACACAGTATATATATG 
                   
               
               
                   
                 TTCTTCAATACGTCAGACATTCGGGAAGCAGTGCCCGAACCCCCATTGCTGTCCCGT 
                   
               
               
                   
                 GCAGAGCTGCGCTTGCAGAGATTAAAATCAAGTGTGGAGCAACATGTGGAACTCTAC 
                   
               
               
                   
                 CAGAAATATAGCAACAATTCCTGGCGTTACCTTGGTAACCGGCTGCTGACCCCCACT 
                   
               
               
                   
                 GATACGCCTGAGTGGCTGTCTTTTGACGTCACTGGAGTTGTACGGCAGTGGCTGAAC 
                   
               
               
                   
                 CAAGGAGACGGAATACAGGGCTTTCGATTCAGCGCTCACTCTTCTTCTGACAGCAAA 
                   
               
               
                   
                 GATAACAAACTCCACGTGGAAATCAACGGGATCAGCCCCAAACGTCGGGGCGACCTG 
                   
               
               
                   
                 GGCACCATCCATGACATGAACCGGCCCTTCCTGCTCCTCATGGCCACCCCCCTGGAA 
                   
               
               
                   
                 AGGGCCCAGCACCTGCACAGCTCACGGCACCGGAGAGCCCTGGATACCAACTATTGC 
                   
               
               
                   
                 TTCAGCTCCACAGAGAAGAACTGCTGTGTGCGGCAGCTGTACATTGACTTTAGGAAG 
                   
               
               
                   
                 GACCTGGGTTGGAAGTGGATCCACGAGCCCAAGGGCTACCATGCCAACTTCTGTCTG 
                   
               
               
                   
                 GGACCCTGCCCCTATATTTGGAGCCTGGACACACAGTACAGCAAGGTCCTTGCCCTC 
                   
               
               
                   
                 TACAACCAACACAACCCGGGCGCTTCGGCGTCACCGTGCTGCGTGCCGCAGGCTTTG 
                   
               
               
                   
                 GAGCCACTGCCCATCGTCTACTACGTGGGTCGCAAGCCCAAGGTGGAGCAGTTGTCC 
                   
               
               
                   
                 AACATGATTGTGCGCTCCTGCAAGTGCAGCGGAGGAGGAGGAAGCGCGTCTGGTGAC 
                   
               
               
                   
                 TTCTGTGACTCCAGCCTGTGCCTGAACGGTGGCACCTGCTTGACGGGCCAAGACAAT 
                   
               
               
                   
                 GACATCTACTGCCTCTGCCCTGAAGGCTTCACAGGCCTTGTGTGCAATGAGACTGAG 
                   
               
               
                   
                 AGAGGACCATGCTCCCCAAACCCTTGCTACAATGATGCCAAATGTCTGGTGACTTTG 
                   
               
               
                   
                 GACACACAGCGTGGGGAAATCTTCACCGAATACATCTGCCAGTGCCCTGTGGGCTAC 
                   
               
               
                   
                 TCGGGCATCCACTGTGAAACCGAGACCAACTACTACAACCTGGATGGAGAATACATG 
                   
               
               
                   
                 TTCACCACAGCCGTCCCCAATACTGCCGTCCCCACCCCGGCCCCCACCCCCGATCTT 
                   
               
               
                   
                 TCCAACAACCTAGCCTCCCGTTGTTCTACACAGCTGGGCATGGAAGGGGGCGCCATT 
                   
               
               
                   
                 GCTGATTCACAGATTTCCGCCTCGTCTGTGTATATGGGTTTCATGGGCTTGCAGCGC 
                   
               
               
                   
                 TGGGGCCCGGAGCTGGCTCGTCTGTACCGCACAGGGATCGTCAATGCCTGGACAGCC 
                   
               
               
                   
                 AGCAACTATGATAGCAAGCCCTGGATCCAGGTGAACCTTCTGCGGAAGATGCGGGTA 
                   
               
               
                   
                 TCAGGTGTGATGACGCAGGGTGCCAGCCGTGCCGGGAGGGCGGAGTACCTGAAGACC 
                   
               
               
                   
                 TTCAAGGTGGCTTACAGCCTCGACGGACGCAAGTTTGAGTTCATCCAGGATGAAAGC 
                   
               
               
                   
                 GGTGGAGACAAGGAGTTTTTGGGTAACCTGGACAACAACAGCCTGAAGGTTAACATG 
                   
               
               
                   
                 TTCAACCCGACTCTGGAGGCACAGTACATAAAGCTGTACCCTGTTTCGTGCCACCGC 
                   
               
               
                   
                 GGCTGCACCCTCCGCTTCGAGCTCCTGGGCTGTGAGTTGCACGGATGTTCTGAGCCC 
                   
               
               
                   
                 CTGGGCCTGAAGAATAACACAATTCCTGACAGCCAGATGTCAGCCTCCAGCAGCTAC 
                   
               
               
                   
                 AAGACATGGAACCTGCGTGCTTTTGGCTGGTACCCCCACTTGGGAAGGCTGGATAAT 
                   
               
               
                   
                 CAGGGCAAGATCAATGCCTGGACGGCTCAGAGCAACAGTGCCAAGGAATGGCTGCAG 
                   
               
               
                   
                 GTTGACCTGGGCACTCAGAGGCAAGTGACAGGAATCATCACCCAGGGGGCCCGTGAC 
                   
               
               
                   
                 TTTGGCCACATCCAGTATGTGGCGTCCTACAAGGTAGCCCACAGTGATGATGGTGTG 
                   
               
               
                   
                 CAGTGGACTGTATATGAGGAGCAAGGAAGCAGCAAGGTCTTCCAGGGCAACTTGGAC 
                   
               
               
                   
                 AACAACTCCCACAAGAAGAACATCTTCGAGAAACCCTTCATGGCTCGCTACGTGCGT 
                   
               
               
                   
                 GTCCTTCCAGTGTCCTGGCATAACCGCATCACCCTGCGCCTGGAGCTGCTGGGCTGT 
                   
               
               
                   
                 TAA 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
             
               
                 TABLE 6 
               
               
                   
               
               
                   
                   
                 SEQ 
               
               
                   
                   
                 ID  
               
               
                   
                 Sequence 
                 NO: 
               
               
                   
               
             
            
               
                 IL-4 
                 HIHGCDKNHLREIIGILNEVTGEGTPCTEMDVPNVLTATKNTTESELVCRASKVLRI 
                 53 
               
               
                 (from 
                 FYLKHGKTPCLKKNSSVLMELQRLFRAFRCLDSSISCTMNESKSTSLKDFLESLKSI 
                   
               
               
                 which 
                 MQMDYS 
                   
               
               
                 signal 
                 CATATCCACGGATGCGACAAAAATCACTTGAGAGAGATCATCGGCATTTTGAACGAG 
                   
               
               
                 peptide  
                 GTCACAGGAGAAGGGACGCCATGCACGGAGATGGATGTGCCAAACGTCCTCACAGCA 
                 54 
               
               
                 is  
                 ACGAAGAACACCACAGAGAGTGAGCTCGTCTGTAGGGCTTCCAAGGTGCTTCGCATA 
                   
               
               
                 removed) 
                 TTTTATTTAAAACATGGGAAAACTCCATGCTTGAAGAAGAACTCTAGTGTTCTCATG 
                   
               
               
                   
                 GAGCTGCAGAGACTCTTTCGGGCTTTTCGATGCCTGGATTCATCGATAAGCTGCACC 
                   
               
               
                   
                 ATGAATGAGTCCAAGTCCACATCACTGAAAGACTTCCTGGAAAGCCTAAAGAGCATC 
                   
               
               
                   
                 ATGCAAATGGATTACTCGTAG 
                   
               
               
                   
               
               
                 CD81 
                 MGVEGCTKCIKYLLFVFNFVFWLAGGVILGVALWLRHDPQTTSLLYLELGNKPAPNT 
                 61 
               
               
                 (amino 
                 FYVGIYILIAVGAVMMFVGFLGCYGAIQESQCLLGTFFTCLVILFACEVAAGIWGFV 
                   
               
               
                 acids 
                 NKDQIAKDVKQFYDQALQQAVMDDDANNAKAVVKTFHETLNCCGSNALTTLTTTILR 
                   
               
               
                 1 to 
                 NSLCPS 
                   
               
               
                 177) 
                 ATGGGGGTGGAGGGCTGCACCAAATGCATCAAATACCTGCTCTTCGTCTTCAATTTC 
                 62 
               
               
                   
                 GTCTTCTGGCTGGCTGGAGGCGTGATCCTAGGTGTAGCTCTGTGGTTGCGTCATGAT 
                   
               
               
                   
                 CCACAGACCACCAGCCTGCTGTACCTGGAACTGGGAAACAAACCGGCACCCAACACC 
                   
               
               
                   
                 TTCTACGTGGGCATCTACATTCTCATTGCTGTGGGAGCTGTGATGATGTTTGTAGGC 
                   
               
               
                   
                 TTCCTGGGGTGCTATGGGGCCATCCAGGAGTCCCAGTGTCTGCTGGGGACGTTCTTC 
                   
               
               
                   
                 ACCTGCCTTGTGATCCTGTTTGCCTGTGAGGTGGCTGCAGGCATCTGGGGCTTCGTA 
                   
               
               
                   
                 AACAAAGACCAGATCGCCAAGGATGTGAAGCAGTTCTATGACCAGGCCCTTCAGCAA 
                   
               
               
                   
                 GCTGTGATGGATGATGATGCCAACAATGCCAAGGCTGTGGTGAAGACTTTCCATGAG 
                   
               
               
                   
                 ACGCTCAACTGTTGTGGCTCCAACGCACTGACCACACTGACTACCACCATACTGAGG 
                   
               
               
                   
                 AACAGCCTGTGTCCCTCA 
                   
               
               
                   
               
               
                 CD81 
                 GGNILTPLLQQDCHQKIDELFSGKLYLIGIAAIVVAVIMIFEMILSMVLCCGIRNSS 
                 63 
               
               
                 (amino 
                 VY 
                   
               
               
                 acids 
                 GGCGGCAACATACTCACCCCCTTACTGCAGCAAGATTGTCATCAGAAAATCGATGAG 
                 64 
               
               
                 178 to  
                 CTCTTCTCTGGGAAGCTGTACCTCATTGGAATTGCAGCCATTGTGGTAGCTGTCATT 
                   
               
               
                 236) 
                 ATGATCTTTGAGATGATTCTGAGCATGGTGCTGTGCTGTGGCATCCGGAACAGCTCC 
                   
               
               
                   
                 GTGTACTGA 
                   
               
               
                   
               
               
                 CD81-  
                 MGVEGCTKCIKYLLFVFNFVFWLAGGVILGVALWLRHDPQTTSLLYLELGNKPAPNT 
                 55 
               
               
                 IL4 
                 FYVGIYILIAVGAVMMFVGFLGCYGAIQESQCLLGTFFTCLVILFACEVAAGIWGFV 
                   
               
               
                   
                 NKDQIAKDVKQFYDQALQQAVMDDDANNAKAVVKTFHETLNCCGSNALTTLTTTILR 
                   
               
               
                   
                 NSLCPSGGGGSHIHGCDKNHLREIIGILNEVTGEGTPCTEMDVPNVLTATKNTTESE 
                   
               
               
                   
                 LVCRASKVLRIFYLKHGKTPCLKKNSSVLMELQRLFRAFRCLDSSISCTMNESKSTS 
                   
               
               
                   
                 LKDFLESLKSIMQMDYSGGGGSGGNILTPLLQQDCHQKIDELFSGKLYLIGIAAIVV 
                   
               
               
                   
                 AVIMIFEMILSMVLCCGIRNSSVY 
                   
               
               
                   
                 ATGGGGGTGGAGGGCTGCACCAAATGCATCAAATACCTGCTCTTCGTCTTCAATTTC 
                 56 
               
               
                   
                 GTCTTCTGGCTGGCTGGAGGCGTGATCCTAGGTGTAGCTCTGTGGTTGCGTCATGAT 
                   
               
               
                   
                 CCACAGACCACCAGCCTGCTGTACCTGGAACTGGGAAACAAACCGGCACCCAACACC 
                   
               
               
                   
                 TTCTACGTGGGCATCTACATTCTCATTGCTGTGGGAGCTGTGATGATGTTTGTAGGC 
                   
               
               
                   
                 TTCCTGGGGTGCTATGGGGCCATCCAGGAGTCCCAGTGTCTGCTGGGGACGTTCTTC 
                   
               
               
                   
                 ACCTGCCTTGTGATCCTGTTTGCCTGTGAGGTGGCTGCAGGCATCTGGGGCTTCGTA 
                   
               
               
                   
                 AACAAAGACCAGATCGCCAAGGATGTGAAGCAGTTCTATGACCAGGCCCTTCAGCAA 
                   
               
               
                   
                 GCTGTGATGGATGATGATGCCAACAATGCCAAGGCTGTGGTGAAGACTTTCCATGAG 
                   
               
               
                   
                 ACGCTCAACTGTTGTGGCTCCAACGCACTGACCACACTGACTACCACCATACTGAGG 
                   
               
               
                   
                 AACAGCCTGTGTCCCTCAGGAGGAGGAGGAAGCCATATCCACGGATGCGACAAAAAT 
                   
               
               
                   
                 CACTTGAGAGAGATCATCGGCATTTTGAACGAGGTCACAGGAGAAGGGACGCCATGC 
                   
               
               
                   
                 ACGGAGATGGATGTGCCAAACGTCCTCACAGCAACGAAGAACACCACAGAGAGTGAG 
                   
               
               
                   
                 CTCGTCTGTAGGGCTTCCAAGGTGCTTCGCATATTTTATTTAAAACATGGGAAAACT 
                   
               
               
                   
                 CCATGCTTGAAGAAGAACTCTAGTGTTCTCATGGAGCTGCAGAGACTCTTTCGGGCT 
                   
               
               
                   
                 TTTCGATGCCTGGATTCATCGATAAGCTGCACCATGAATGAGTCCAAGTCCACATCA 
                   
               
               
                   
                 CTGAAAGACTTCCTGGAAAGCCTAAAGAGCATCATGCAAATGGATTACTCGGGAGGA 
                   
               
               
                   
                 GGAGGAAGCGGCGGCAACATACTCACCCCCTTACTGCAGCAAGATTGTCATCAGAAA 
                   
               
               
                   
                 ATCGATGAGCTCTTCTCTGGGAAGCTGTACCTCATTGGAATTGCAGCCATTGTGGTA 
                   
               
               
                   
                 GCTGTCATTATGATCTTTGAGATGATTCTGAGCATGGTGCTGTGCTGTGGCATCCGG 
                   
               
               
                   
                 AACAGCTCCGTGTACTGA 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
             
               
                 TABLE 7 
               
               
                   
               
               
                   
                   
                 SEQ 
               
               
                   
                   
                 ID  
               
               
                   
                 Sequence 
                 NO: 
               
               
                   
               
             
            
               
                 Signal  
                 
                   MALQIPSLLLSAAVVVLMVLSSPGTEG 
                 
                 33 
               
               
                 peptide 
                 
                   ATGGCTCTGCAGATCCCCAGCCTCCTCCTCTCGGCTGCTGTGGTGGTGCTGATGGTGCTGAGC 
                 
                 34 
               
               
                 of MHC 
                 
                   AGCCCAGGGACTGAGGGC 
                 
                   
               
               
                 class IIβ 
                   
                   
               
               
                 chain 
                   
                   
               
               
                   
               
               
                 OVA 
                 ISQAVHAAHAEINEAGR 
                 35 
               
               
                 peptide 2  
                 ATATCTCAAGCTGTCCATGCAGCACATGCAGAAATCAATGAAGCAGGCAGA 
                   
               
               
                 (for MHC 
                   
                   
               
               
                 class II 
                   
                   
               
               
                 molecule) 
                   
                   
               
               
                   
               
               
                 MHC  
                 GDSERHFVYQFMGECYFTNGTQRIRYVTRYIYNREEYVRYDSDVGEHRAVTELGRPDAEYWNS 
                 36 
               
               
                 class IIβ 
                 QPEILERTRAELDTVCRHNYEGPETHTSLRRLEQPNVVISLSRTEALNHHNTLVCSVTDFYPA 
                   
               
               
                 chain 
                 KIKVRWFRNGQEETVGVSSTQLIRNGDWTFQVLVMLEMTPRRGEVYTCHVEHPSLKSPITVEW 
                   
               
               
                 (from 
                 RAQSESAWSKMLSGIGGCVLGVIFLGLGLFIRHRSQKGPRGPPPAGLLQ 
                   
               
               
                 which  
                 GGAGACTCCGAAAGGCATTTCGTGTACCAGTTCATGGGCGAGTGCTACTTCACCAACGGGACG 
                 37 
               
               
                 signal 
                 CAGCGCATACGATATGTGACCAGATACATCTACAACCGGGAGGAGTACGTGCGCTACGACAGC 
                   
               
               
                 peptide 
                 GACGTGGGCGAGCACCGCGCGGTGACCGAGCTGGGGCGGCCAGACGCCGAGTACTGGAACAGC 
                   
               
               
                 is  
                 CAGCCGGAGATCCTGGAGCGAACGCGGGCCGAGCTGGACACGGTGTGCAGACACAACTACGAG 
                   
               
               
                 removed) 
                 GGGCCGGAGACCCACACCTCCCTGCGGCGGCTTGAACAGCCCAATGTCGTCATCTCCCTGTCC 
                   
               
               
                   
                 AGGACAGAGGCCCTCAACCACCACAACACTCTGGTCTGCTCAGTGACAGATTTCTACCCAGCC 
                   
               
               
                   
                 AAGATCAAAGTGCGCTGGTTCCGGAATGGCCAGGAGGAGACGGTGGGGGTCTCATCCACACAG 
                   
               
               
                   
                 CTTATTAGGAATGGGGACTGGACCTTCCAGGTCCTGGTCATGCTGGAGATGACCCCTCGGCGG 
                   
               
               
                   
                 GGAGAGGTCTACACCTGTCACGTGGAGCATCCCAGCCTGAAGAGCCCCATCACTGTGGAGTGG 
                   
               
               
                   
                 AGGGCACAGTCTGAGTCTGCCTGGAGCAAGATGTTGAGCGGCATCGGGGGCTGCGTGCTTGGG 
                   
               
               
                   
                 GTGATCTTCCTCGGGCTTGGCCTTTTCATCCGTCACAGGAGTCAGAAAGGACCTCGAGGCCCT 
                   
               
               
                   
                 CCTCCAGCAGGGCTCCTGCAG 
                   
               
               
                   
               
               
                 Peptide  
                 GGGGSGGGGSG 
                 39 
               
               
                 linker 4 
                 GGAGGAGGAGGAAGCGGAGGAGGAGGAAGCGGA 
                 40 
               
               
                   
               
               
                 sc-    
                   MALQIPSLLLSAAVVVLMVLSSPGTEG ISQAVHAAHAEINEAGRGGGGSGGGGSGGDSERHFV 
                 41 
               
               
                 Dimer 
                 YQFMGECYFTNGTQRIRYVTRYIYNREEYVRYDSDVGEHRAVTELGRPDAEYWNSQPEILERT 
                   
               
               
                 (OVA 
                 RAELDTVCRHNYEGPETHTSLRRLEQPNVVISLSRTEALNHHNTLVCSVTDFYPAKIKVRWFR 
                   
               
               
                 peptide  
                 NGQEETVGVSSTQLIRNGDWTFQVLVMLEMTPRRGEVYTCHVEHPSLKSPITVEWRAQSESAW 
                   
               
               
                 2 + 
                 SKMLSGIGGCVLGVIFLGLGLFIRHRSQKGPRGPPPAGLLQ 
                   
               
               
                 peptide  
                 
                   ATGGCTCTGCAGATCCCCAGCCTCCTCCTCTCGGCTGCTGTGGTGGTGCTGATGGTGCTGAGC 
                 
                 42 
               
               
                 linker 
                   AGCCCAGGGACTGAGGGC ATATCTCAAGCTGTCCATGCAGCACATGCAGAAATCAATGAAGCA 
                   
               
               
                 4 + MHC 
                 GGCAGAGGAGGAGGAGGAAGCGGAGGAGGAGGAAGCGGAGGAGACTCCGAAAGGCATTTCGTG 
                   
               
               
                 class IIβ  
                 TACCAGTTCATGGGCGAGTGCTACTTCACCAACGGGACGCAGCGCATACGATATGTGACCAGA 
                   
               
               
                 chain 
                 TACATCTACAACCGGGAGGAGTACGTGCGCTACGACAGCGACGTGGGCGAGCACCGCGCGGTG 
                   
               
               
                 (from  
                 ACCGAGCTGGGGCGGCCAGACGCCGAGTACTGGAACAGCCAGCCGGAGATCCTGGAGCGAACG 
                   
               
               
                 which 
                 CGGGCCGAGCTGGACACGGTGTGCAGACACAACTACGAGGGGCCGGAGACCCACACCTCCCTG 
                   
               
               
                 signal 
                 CGGCGGCTTGAACAGCCCAATGTCGTCATCTCCCTGTCCAGGACAGAGGCCCTCAACCACCAC 
                   
               
               
                 peptide 
                 AACACTCTGGTCTGCTCAGTGACAGATTTCTACCCAGCCAAGATCAAAGTGCGCTGGTTCCGG 
                   
               
               
                 is  
                 AATGGCCAGGAGGAGACGGTGGGGGTCTCATCCACACAGCTTATTAGGAATGGGGACTGGACC 
                   
               
               
                 removed)) 
                 TTCCAGGTCCTGGTCATGCTGGAGATGACCCCTCGGCGGGGAGAGGTCTACACCTGTCACGTG 
                   
               
               
                   
                 GAGCATCCCAGCCTGAAGAGCCCCATCACTGTGGAGTGGAGGGCACAGTCTGAGTCTGCCTGG 
                   
               
               
                   
                 AGCAAGATGTTGAGCGGCATCGGGGGCTGCGTGCTTGGGGTGATCTTCCTCGGGCTTGGCCTT 
                   
               
               
                   
                 TTCATCCGTCACAGGAGTCAGAAAGGACCTCGAGGCCCTCCTCCAGCAGGGCTCCTGCAG 
                   
               
               
                   
               
               
                 sc-    
                   MALQIPSLLLSAAVVVLMVLSSPGTEG ISQAVHAAHAEINEAGRGGGGSGGGGSGGDSERHFV 
                 91 
               
               
                 Dimer- 
                 YQFMGECYFTNGTQRIRYVTRYIYNREEYVRYDSDVGEHRAVTELGRPDAEYWNSQPEILERT 
                   
               
               
                 CD81- 
                 RAELDTVCRHNYEGPETHTSLRRLEQPNVVISLSRTEALNHHNTLVCSVTDFYPAKIKVRWFR 
                   
               
               
                 IL-12α 
                 NGQEETVGVSSTQLIRNGDWTFQVLVMLEMTPRRGEVYTCHVEHPSLKSPITVEWRAQSESAW 
                   
               
               
                   
                 SKMLSGIGGCVLGVIFLGLGLFIRHRSQKGPRGPPPAGLLQMGVEGCTKCIKYLLFVFNFVFW 
                   
               
               
                   
                 LAGGVILGVALWLRHDPQTTSLLYLELGNKPAPNTFYVGIYILIAVGAVMMFVGFLGCYGAIQ 
                   
               
               
                   
                 ESQCLLGTFFTCLVILFACEVAAGIWGFVNKDQIAKDVKQFYDQALQQAVMDDDANNAKAVVK 
                   
               
               
                   
                 TFHETLNCCGSNALTTLTTTILRNSLCPSGGGGSRVIPVSGPARCLSQSRNLLKTTDDMVKTA 
                   
               
               
                   
                 REKLKHYSCTAEDIDHEDITRDQTSTLKTCLPLELHKNESCLATRETSSTTRGSCLPPQKTSL 
                   
               
               
                   
                 MMTLCLGSIYEDLKMYQTEFQAINAALQNHNHQQIILDKGMLVAIDELMQSLNHNGETLRQKP 
                   
               
               
                   
                 PVGEADPYRVKMKLCILLHAFSTRVVTINRVMGYLSSAGGGGSGGNILTPLLQQDCHQKIDEL 
                   
               
               
                   
                 FSGKLYLIGIAAIVVAVIMIFEMILSMVLCCGIRNSSVY 
                   
               
               
                   
                 
                   ATGGCTCTGCAGATCCCCAGCCTCCTCCTCTCGGCTGCTGTGGTGGTGCTGATGGTGCTGAGC 
                 
                 92 
               
               
                   
                   AGCCCAGGGACTGAGGGC ATATCTCAAGCTGTCCATGCAGCACATGCAGAAATCAATGAAGCA 
                   
               
               
                   
                 GGCAGAGGAGGAGGAGGAAGCGGAGGAGGAGGAAGCGGAGGAGACTCCGAAAGGCATTTCGTG 
                   
               
               
                   
                 TACCAGTTCATGGGCGAGTGCTACTTCACCAACGGGACGCAGCGCATACGATATGTGACCAGA 
                   
               
               
                   
                 TACATCTACAACCGGGAGGAGTACGTGCGCTACGACAGCGACGTGGGCGAGCACCGCGCGGTG 
                   
               
               
                   
                 ACCGAGCTGGGGCGGCCAGACGCCGAGTACTGGAACAGCCAGCCGGAGATCCTGGAGCGAACG 
                   
               
               
                   
                 CGGGCCGAGCTGGACACGGTGTGCAGACACAACTACGAGGGGCCGGAGACCCACACCTCCCTG 
                   
               
               
                   
                 CGGCGGCTTGAACAGCCCAATGTCGTCATCTCCCTGTCCAGGACAGAGGCCCTCAACCACCAC 
                   
               
               
                   
                 AACACTCTGGTCTGCTCAGTGACAGATTTCTACCCAGCCAAGATCAAAGTGCGCTGGTTCCGG 
                   
               
               
                   
                 AATGGCCAGGAGGAGACGGTGGGGGTCTCATCCACACAGCTTATTAGGAATGGGGACTGGACC 
                   
               
               
                   
                 TTCCAGGTCCTGGTCATGCTGGAGATGACCCCTCGGCGGGGAGAGGTCTACACCTGTCACGTG 
                   
               
               
                   
                 GAGCATCCCAGCCTGAAGAGCCCCATCACTGTGGAGTGGAGGGCACAGTCTGAGTCTGCCTGG 
                   
               
               
                   
                 AGCAAGATGTTGAGCGGCATCGGGGGCTGCGTGCTTGGGGTGATCTTCCTCGGGCTTGGCCTT 
                   
               
               
                   
                 TTCATCCGTCACAGGAGTCAGAAAGGACCTCGAGGCCCTCCTCCAGCAGGGCTCCTGCAGATG 
                   
               
               
                   
                 GGGGTGGAGGGCTGCACCAAATGCATCAAATACCTGCTCTTCGTCTTCAATTTCGTCTTCTGG 
                   
               
               
                   
                 CTGGCTGGAGGCGTGATCCTAGGTGTAGCTCTGTGGTTGCGTCATGATCCACAGACCACCAGC 
                   
               
               
                   
                 CTGCTGTACCTGGAACTGGGAAACAAACCGGCACCCAACACCTTCTACGTGGGCATCTACATT 
                   
               
               
                   
                 CTCATTGCTGTGGGAGCTGTGATGATGTTTGTAGGCTTCCTGGGGTGCTATGGGGCCATCCAG 
                   
               
               
                   
                 GAGTCCCAGTGTCTGCTGGGGACGTTCTTCACCTGCCTTGTGATCCTGTTTGCCTGTGAGGTG 
                   
               
               
                   
                 GCTGCAGGCATCTGGGGCTTCGTAAACAAAGACCAGATCGCCAAGGATGTGAAGCAGTTCTAT 
                   
               
               
                   
                 GACCAGGCCCTTCAGCAAGCTGTGATGGATGATGATGCCAACAATGCCAAGGCTGTGGTGAAG 
                   
               
               
                   
                 ACTTTCCATGAGACGCTCAACTGTTGTGGCTCCAACGCACTGACCACACTGACTACCACCATA 
                   
               
               
                   
                 CTGAGGAACAGCCTGTGTCCCTCAGGAGGAGGAGGAAGCAGGGTCATTCCAGTCTCTGGACCT 
                   
               
               
                   
                 GCCAGGTGTCTTAGCCAGTCCCGAAACCTGCTGAAGACCACAGATGACATGGTGAAGACGGCC 
                   
               
               
                   
                 AGAGAAAAACTGAAACATTATTCCTGCACTGCTGAAGACATCGATCATGAAGACATCACACGG 
                   
               
               
                   
                 GACCAAACCAGCACATTGAAGACCTGTTTACCACTGGAACTACACAAGAACGAGAGTTGCCTG 
                   
               
               
                   
                 GCTACTAGAGAGACTTCTTCCACAACAAGAGGGAGCTGCCTGCCCCCACAGAAGACGTCTTTG 
                   
               
               
                   
                 ATGATGACCCTGTGCCTTGGTAGCATCTATGAGGACTTGAAGATGTACCAGACAGAGTTCCAG 
                   
               
               
                   
                 GCCATCAACGCAGCACTTCAGAATCACAACCATCAGCAGATCATTCTAGACAAGGGCATGCTG 
                   
               
               
                   
                 GTGGCCATCGATGAGCTGATGCAGTCTCTGAATCATAATGGCGAGACTCTGCGCCAGAAACCT 
                   
               
               
                   
                 CCTGTGGGAGAAGCAGACCCTTACAGAGTGAAAATGAAGCTCTGCATCCTGCTTCACGCCTTC 
                   
               
               
                   
                 AGCACCCGCGTCGTGACCATCAACAGGGTGATGGGCTATCTGAGCTCCGCCGGAGGAGGAGGA 
                   
               
               
                   
                 AGCGGCGGCAACATACTCACCCCCTTACTGCAGCAAGATTGTCATCAGAAAATCGATGAGCTC 
                   
               
               
                   
                 TTCTCTGGGAAGCTGTACCTCATTGGAATTGCAGCCATTGTGGTAGCTGTCATTATGATCTTT 
                   
               
               
                   
                 GAGATGATTCTGAGCATGGTGCTGTGCTGTGGCATCCGGAACAGCTCCGTGTACTGA 
                   
               
               
                   
               
               
                 MHC  
                   MPRSRALILGVLALTTMLSLCGG EDDIEADHVGTYGISVYQSPGDIGQYTFEFDGDELFYVDL 
                 45 
               
               
                 class IIα 
                 DKKETVWMLPEFGQLASFDPQGGLQNIAVVKHNLGVLTKRSNSTPATNEAPQATVFPKSPVLL 
                   
               
               
                 chain 
                 GQPNTLICFVDNIFPPVINITWLRNSKSVADGVYETSFFVNRDYSFHKLSYLTFIPSDDDIYD 
                   
               
               
                   
                 CKVEHWGLEEPVLKHWEPEIPAPMSELTETVVCALGLSVGLVGIVVGTIFIIQGLRSGGTSRH 
                   
               
               
                   
                 PGPL 
                   
               
               
                   
                 
                   ATGCCGCGCAGCAGAGCTCTGATTCTGGGGGTCCTCGCCCTGACCACCATGCTCAGCCTCTGT 
                 
                 46 
               
               
                   
                   GGAGGT GAAGACGACATTGAGGCCGACCACGTAGGCACCTATGGTATAAGTGTATATCAGTCT 
                   
               
               
                   
                 CCTGGAGACATTGGCCAGTACACATTTGAATTTGATGGTGATGAGTTGTTCTATGTGGACTTG 
                   
               
               
                   
                 GATAAGAAGGAGACTGTCTGGATGCTTCCTGAGTTTGGCCAATTGGCAAGCTTTGACCCCCAA 
                   
               
               
                   
                 GGTGGACTGCAAAACATAGCTGTAGTAAAACACAACTTGGGAGTCTTGACTAAGAGGTCAAAT 
                   
               
               
                   
                 TCCACCCCAGCTACCAATGAGGCTCCTCAAGCGACTGTGTTCCCCAAGTCCCCTGTGCTGCTG 
                   
               
               
                   
                 GGTCAGCCCAACACCCTCATCTGCTTTGTGGACAACATCTTCCCTCCTGTGATCAACATCACA 
                   
               
               
                   
                 TGGCTCAGAAATAGCAAGTCAGTCGCAGACGGTGTTTATGAGACCAGCTTCTTCGTCAACCGT 
                   
               
               
                   
                 GACTATTCCTTCCACAAGCTGTCTTATCTCACCTTCATCCCTTCTGACGATGACATTTATGAC 
                   
               
               
                   
                 TGCAAGGTGGAACACTGGGGCCTGGAGGAGCCGGTTCTGAAACACTGGGAACCTGAGATTCCA 
                   
               
               
                   
                 GCCCCCATGTCAGAGCTGACAGAGACTGTGGTCTGTGCCCTGGGGTTGTCTGTGGGCCTTGTG 
                   
               
               
                   
                 GGCATCGTGGTGGGCACCATCTTCATCATTCAAGGCCTGCGATCAGGTGGCACCTCCAGACAC 
                   
               
               
                   
                 CCAGGGCCTTTATGA 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
             
               
                 TABLE 8 
               
               
                   
               
               
                   
                   
                 SEQ 
               
               
                   
                   
                 ID 
               
               
                   
                 Sequence 
                 NO: 
               
               
                   
               
             
            
               
                 IL-12α 
                 RVIPVSGPARCLSQSRNLLKTTDDMVKTAREKLKHYSCTAEDIDHEDITRDQTSTLKTCLPLE 
                 93 
               
               
                 (from  
                 LHKNESCLATRETSSTTRGSCLPPQKTSLMMTLCLGSIYEDLKMYQTEFQAINAALQNHNHQQ 
                   
               
               
                 which  
                 IILDKGMLVAIDELMQSLNHNGETLRQKPPVGEADPYRVKMKLCILLHAFSTRVVTINRVMGY 
                   
               
               
                 signal 
                 LSSA 
                   
               
               
                 peptide 
                 AGGGTCATTCCAGTCTCTGGACCTGCCAGGTGTCTTAGCCAGTCCCGAAACCTGCTGAAGACC 
                 94 
               
               
                 is 
                 ACAGATGACATGGTGAAGACGGCCAGAGAAAAACTGAAACATTATTCCTGCACTGCTGAAGAC 
                   
               
               
                 removed) 
                 ATCGATCATGAAGACATCACACGGGACCAAACCAGCACATTGAAGACCTGTTTACCACTGGAA 
                   
               
               
                   
                 CTACACAAGAACGAGAGTTGCCTGGCTACTAGAGAGACTTCTTCCACAACAAGAGGGAGCTGC 
                   
               
               
                   
                 CTGCCCCCACAGAAGACGTGTTTGATGATGACCCTGTGCCTTGGTAGCATCTATGAGGACTTG 
                   
               
               
                   
                 AAGATGTACCAGACAGAGTTCCAGGCCATCAACGCAGCACTTCAGAATCACAACCATCAGCAG 
                   
               
               
                   
                 ATCATTCTAGACAAGGGCATGCTGGTGGCCATCGATGAGCTGATGCAGTCTCTGAATCATAAT 
                   
               
               
                   
                 GGCGAGACTCTGCGCCAGAAACCTCCTGTGGGAGAAGCAGACCCTTACAGAGTGAAAATGAAG 
                   
               
               
                   
                 CTCTGCATCCTGCTTCACGCCTTCAGCACCCGCGTCGTGACCATCAACAGGGTGATGGGCTAT 
                   
               
               
                   
                 CTGAGCTCCGCC 
                   
               
               
                   
               
               
                 CD81 
                 MGVEGCTKCIKYLLFVFNFVFWLAGGVILGVALWLRHDPQTTSLLYLELGNKPAPNTFYVGIY 
                 61 
               
               
                 (amino  
                 ILIAVGAVMMFVGFLGCYGAIQESQCLLGTFFTCLVILFACEVAAGIWGFVNKDQIAKDVKQF 
                   
               
               
                 acids  
                 YDQALQQAVMDDDANNAKAVVKTFHETLNCCGSNALTTLTTTILRNSLCPS 
                   
               
               
                 1 to 
                 ATGGGGGTGGAGGGCTGCACCAAATGCATCAAATACCTGCTCTTCGTCTTCAATTTCGTCTTC 
                 62 
               
               
                 177) 
                 TGGCTGGCTGGAGGCGTGATCCTAGGTGTAGCTCTGTGGTTGCGTCATGATCCACAGACCACC 
                   
               
               
                   
                 AGCCTGCTGTACCTGGAACTGGGAAACAAACCGGCACCCAACACCTTCTACGTGGGCATCTAC 
                   
               
               
                   
                 ATTCTCATTGCTGTGGGAGCTGTGATGATGTTTGTAGGCTTCCTGGGGTGCTATGGGGCCATC 
                   
               
               
                   
                 CAGGAGTCCCAGTGTCTGCTGGGGACGTTCTTCACCTGCCTTGTGATCCTGTTTGCCTGTGAG 
                   
               
               
                   
                 GTGGCTGCAGGCATCTGGGGCTTCGTAAACAAAGACCAGATCGCCAAGGATGTGAAGCAGTTC 
                   
               
               
                   
                 TATGACCAGGCCCTTCAGCAAGCTGTGATGGATGATGATGCCAACAATGCCAAGGCTGTGGTG 
                   
               
               
                   
                 AAGACTTTCCATGAGACGCTCAACTGTTGTGGCTCCAACGCACTGACCACACTGACTACCACC 
                   
               
               
                   
                 ATACTGAGGAACAGCCTGTGTCCCTCA 
                   
               
               
                   
               
               
                 CD81 
                 GGNILTPLLQQDCHQKIDELFSGKLYLIGIAAIVVAVIMIFEMILSMVLCCGIRNSSVY 
                 63 
               
               
                 (amino  
                 GGCGGCAACATACTCACCCCCTTACTGCAGCAAGATTGTCATCAGAAAATCGATGAGCTCTTC 
                 64 
               
               
                 acids  
                 TCTGGGAAGCTGTACCTCATTGGAATTGCAGCCATTGTGGTAGCTGTCATTATGATCTTTGAG 
                   
               
               
                 178 to 
                 ATGATTCTGAGCATGGTGCTGTGCTGTGGCATCCGGAACAGCTCCGTGTACTGA 
                   
               
               
                 236) 
                   
                   
               
               
                   
               
               
                 CD81-IL- 
                 MGVEGCTKCIKYLLFVFNFVFWLAGGVILGVALWLRHDPQTTSLLYLELGNKPAPNTFYVGIY 
                 95 
               
               
                 12α 
                 ILIAVGAVMMFVGFLGCYGAIQESQCLLGTFFTCLVILFACEVAAGIWGFVNKDQIAKDVKQF 
                   
               
               
                   
                 YDQALQQAVMDDDANNAKAVVKTFHETLNCCGSNALTTLTTTILRNSLCPSGGGGSRVIPVSG 
                   
               
               
                   
                 PARCLSQSRNLLKTTDDMVKTAREKLKHYSCTAEDIDHEDITRDQTSTLKTCLPLELHKNESC 
                   
               
               
                   
                 LATRETSSTTRGSCLPPQKTSLMMTLCLGSIYEDLKMYQTEFQAINAALQNHNHQQIILDKGM 
                   
               
               
                   
                 LVAIDELMQSLNHNGETLRQKPPVGEADPYRVKMKLCILLHAFSTRVVTINRVMGYLSSAGGG 
                   
               
               
                   
                 GSGGNILTPLLQQDCHQKIDELFSGKLYLIGIAAIVVAVIMIFEMILSMVLCCGIRNSSVY 
                   
               
               
                   
                 ATGGGGGTGGAGGGCTGCACCAAATGCATCAAATACCTGCTCTTCGTCTTCAATTTCGTCTTC 
                 96 
               
               
                   
                 TGGCTGGCTGGAGGCGTGATCCTAGGTGTAGCTCTGTGGTTGCGTCATGATCCACAGACCACC 
                   
               
               
                   
                 AGCCTGCTGTACCTGGAACTGGGAAACAAACCGGCACCCAACACCTTCTACGTGGGCATCTAC 
                   
               
               
                   
                 ATTCTCATTGCTGTGGGAGCTGTGATGATGTTTGTAGGCTTCCTGGGGTGCTATGGGGCCATC 
                   
               
               
                   
                 CAGGAGTCCCAGTGTCTGCTGGGGACGTTCTTCACCTGCCTTGTGATCCTGTTTGCCTGTGAG 
                   
               
               
                   
                 GTGGCTGCAGGCATCTGGGGCTTCGTAAACAAAGACCAGATCGCCAAGGATGTGAAGCAGTTC 
                   
               
               
                   
                 TATGACCAGGCCCTTCAGCAAGCTGTGATGGATGATGATGCCAACAATGCCAAGGCTGTGGTG 
                   
               
               
                   
                 AAGACTTTCCATGAGACGCTCAACTGTTGTGGCTCCAACGCACTGACCACACTGACTACCACC 
                   
               
               
                   
                 ATACTGAGGAACAGCCTGTGTCCCTCAGGAGGAGGAGGAAGCAGGGTCATTCCAGTCTCTGGA 
                   
               
               
                   
                 CCTGCCAGGTGTCTTAGCCAGTCCCGAAACCTGCTGAAGACCACAGATGACATGGTGAAGACG 
                   
               
               
                   
                 GCCAGAGAAAAACTGAAACATTATTCCTGCACTGCTGAAGACATCGATCATGAAGACATCACA 
                   
               
               
                   
                 CGGGACCAAACCAGCACATTGAAGACCTGTTTACCACTGGAACTACACAAGAACGAGAGTTGC 
                   
               
               
                   
                 CTGGCTACTAGAGAGACTTCTTCCACAACAAGAGGGAGCTGCCTGCCCCCACAGAAGACGTCT 
                   
               
               
                   
                 TTGATGATGACCCTGTGCCTTGGTAGCATCTATGAGGACTTGAAGATGTACCAGACAGAGTTC 
                   
               
               
                   
                 CAGGCCATCAACGCAGCACTTCAGAATCACAACCATCAGCAGATCATTCTAGACAAGGGCATG 
                   
               
               
                   
                 CTGGTGGCCATCGATGAGCTGATGCAGTCTCTGAATCATAATGGCGAGACTCTGCGCCAGAAA 
                   
               
               
                   
                 CCTCCTGTGGGAGAAGCAGACCCTTACAGAGTGAAAATGAAGCTCTGCATCCTGCTTCACGCC 
                   
               
               
                   
                 TTCAGCACCCGCGTCGTGACCATCAACAGGGTGATGGGCTATCTGAGCTCCGCCGGAGGAGGA 
                   
               
               
                   
                 GGAAGCGGCGGCAACATACTCACCCCCTTACTGCAGCAAGATTGTCATCAGAAAATCGATGAG 
                   
               
               
                   
                 CTCTTCTCTGGGAAGCTGTACCTCATTGGAATTGCAGCCATTGTGGTAGCTGTCATTATGATC 
                   
               
               
                   
                 TTTGAGATGATTCTGAGCATGGTGCTGTGCTGTGGCATCCGGAACAGCTCCGTGTACTGA 
                   
               
               
                   
               
               
                 IL-12β 
                 MCPQKLTISWFAIVLLVSPLMAMWELEKDVYVVEVDWTPDAPGETVNLTCDTPEEDDITWTSD 
                 97 
               
               
                   
                 QRHGVIGSGKTLTITVKEFLDAGQYTCHKGGETLSHSHLLLHKKENGIWSTEILKNFKNKTFL 
                   
               
               
                   
                 KCEAPNYSGRFTCSWLVQRNMDLKFNIKSSSSSPDSRAVTCGMASLSAEKVTLDQRDYEKYSV 
                   
               
               
                   
                 SCQEDVTCPTAEETLPIELALEARQQNKYENYSTSFFIRDIIKPDPPKNLQMKPLKNSQVEVS 
                   
               
               
                   
                 WEYPDSWSTPHSYFSLKFFVRIQRKKEKMKETEEGCNQKGAFLVEKTSTEVQCKGGNVCVQAQ 
                   
               
               
                   
                 DRYYNSSCSKWACVPCRVRS 
                   
               
               
                   
                 ATGTGTCCTCAGAAGCTAACCATCTCCTGGTTTGCCATCGTTTTGCTGGTGTCTCCACTCATG 
                 98 
               
               
                   
                 GCCATGTGGGAGCTGGAGAAAGACGTTTATGTTGTAGAGGTGGACTGGACTCCCGATGCCCCT 
                   
               
               
                   
                 GGAGAAACAGTGAACCTCACCTGTGACACGCCTGAAGAAGATGACATCACCTGGACCTCAGAC 
                   
               
               
                   
                 CAGAGACATGGAGTCATAGGCTCTGGAAAGACCCTGACCATCACTGTCAAAGAGTTTCTAGAT 
                   
               
               
                   
                 GCTGGCCAGTACACCTGCCACAAAGGAGGCGAGACTCTGAGCCACTCACATCTGCTGCTCCAC 
                   
               
               
                   
                 AAGAAGGAAAATGGAATTTGGTCCACTGAAATTTTAAAAAATTTCAAAAACAAGACTTTCCTG 
                   
               
               
                   
                 AAGTGTGAAGCACCAAATTACTCCGGACGGTTCACGTGCTCATGGCTGGTGCAAAGAAACATG 
                   
               
               
                   
                 GACTTGAAGTTCAACATCAAGAGCAGTAGCAGTTCCCCTGACTCTCGGGCAGTGACATGTGGA 
                   
               
               
                   
                 ATGGCGTCTCTGTCTGCAGAGAAGGTCACACTGGACCAAAGGGACTATGAGAAGTATTCAGTG 
                   
               
               
                   
                 TCCTGCCAGGAGGATGTCACCTGCCCAACTGCCGAGGAGACCCTGCCCATTGAACTGGCGTTG 
                   
               
               
                   
                 GAAGCACGGCAGCAGAATAAATATGAGAACTACAGCACCAGCTTCTTCATCAGGGACATCATC 
                   
               
               
                   
                 AAACCAGACCCGCCCAAGAACTTGCAGATGAAGCCTTTGAAGAACTCACAGGTGGAGGTCAGC 
                   
               
               
                   
                 TGGGAGTACCCTGACTCCTGGAGCACTCCCCATTCCTACTTCTCCCTCAAGTTCTTTGTTCGA 
                   
               
               
                   
                 ATCCAGCGCAAGAAAGAAAAGATGAAGGAGACAGAGGAGGGGTGTAACCAGAAAGGTGCGTTC 
                   
               
               
                   
                 CTCGTAGAGAAGACATCTACCGAAGTCCAATGCAAAGGCGGGAATGTCTGCGTGCAAGCTCAG 
                   
               
               
                   
                 GATCGCTATTACAATTCCTCATGCAGCAAGTGGGCATGTGTTCCCTGCAGGGTCCGATCCTAG 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
             
               
                 TABLE 9 
               
               
                   
               
               
                   
                   
                 SEQ 
               
               
                   
                   
                 ID 
               
               
                   
                 Sequence 
                 NO: 
               
               
                   
               
             
            
               
                 IL-6 
                 FPTSQVRRGDFTEDTTPNRPVYTTSQVGGLITHVLWEIVEMRKELCNGNSDCMNNDDALAENN 
                  99 
               
               
                 (from 
                 LKLPEIQRNDGCYQTGYNQEICLLKISSGLLEYHSYLEYMKNNLKDNKKDKARVLQRDTETLI 
                   
               
               
                 which 
                 HIFNQEVKDLHKIVLPTPISNALLTDKLESQKEWLRTKTIQFILKSLEEFLKVTLRSTRQT 
                   
               
               
                 signal 
                 TTCCCTACTTCACAAGTCCGGAGAGGAGACTTCACAGAGGATACCACTCCCAACAGACCTGTC 
                 100 
               
               
                 peptide 
                 TATACCACTTCACAAGTCGGAGGCTTAATTACACATGTTCTCTGGGAAATCGTGGAAATGAGA 
                   
               
               
                 is 
                 AAAGAGTTGTGCAATGGCAATTCTGATTGTATGAACAACGATGATGCACTTGCAGAAAACAAT 
                   
               
               
                 removed)  
                 CTGAAACTTCCAGAGATACAAAGAAATGATGGATGCTACCAAACTGGATATAATCAGGAAATT 
                   
               
               
                   
                 TGCCTATTGAAAATTTCCTCTGGTCTTCTGGAGTACCATAGCTACCTGGAGTACATGAAGAAC 
                   
               
               
                   
                 AACTTAAAAGATAACAAGAAAGACAAAGCCAGAGTCCTTCAGAGAGATACAGAAACTCTAATT 
                   
               
               
                   
                 CATATCTTCAACCAAGAGGTAAAAGATTTACATAAAATAGTCCTTCCTACCCCAATTTCCAAT 
                   
               
               
                   
                 GCTCTCCTAACAGATAAGCTGGAGTCACAGAAGGAGTGGCTAAGGACCAAGACCATCCAATTC 
                   
               
               
                   
                 ATCTTGAAATCACTTGAAGAATTTCTAAAAGTCACTTTGAGATCTACTCGGCAAACC 
                   
               
               
                   
               
               
                 CD81 
                 MGVEGCTKCIKYLLFVFNFVFWLAGGVILGVALWLRHDPQTTSLLYLELGNKPAPNTFYVGIY 
                  61 
               
               
                 (amino 
                 ILIAVGAVMMFVGFLGCYGAIQESQCLLGTFFTCLVILFACEVAAGIWGFVNKDQIAKDVKQF 
                   
               
               
                 acids 
                 YDQALQQAVMDDDANNAKAVVKTFHETLNCCGSNALTTLTTTILRNSLCPS 
                   
               
               
                 1 to 
                 ATGGGGGTGGAGGGCTGCACCAAATGCATCAAATACCTGCTCTTCGTCTTCAATTTCGTCTTC 
                  62 
               
               
                 177) 
                 TGGCTGGCTGGAGGCGTGATCCTAGGTGTAGCTCTGTGGTTGCGTCATGATCCACAGACCACC 
                   
               
               
                   
                 AGCCTGCTGTACCTGGAACTGGGAAACAAACCGGCACCCAACACCTTCTACGTGGGCATCTAC 
                   
               
               
                   
                 ATTCTCATTGCTGTGGGAGCTGTGATGATGTTTGTAGGCTTCCTGGGGTGCTATGGGGCCATC 
                   
               
               
                   
                 CAGGAGTCCCAGTGTCTGCTGGGGACGTTCTTCACCTGCCTTGTGATCCTGTTTGCCTGTGAG 
                   
               
               
                   
                 GTGGCTGCAGGCATCTGGGGCTTCGTAAACAAAGACCAGATCGCCAAGGATGTGAAGCAGTTC 
                   
               
               
                   
                 TATGACCAGGCCCTTCAGCAAGCTGTGATGGATGATGATGCCAACAATGCCAAGGCTGTGGTG 
                   
               
               
                   
                 AAGACTTTCCATGAGACGCTCAACTGTTGTGGCTCCAACGCACTGACCACACTGACTACCACC 
                   
               
               
                   
                 ATACTGAGGAACAGCCTGTGTCCCTCA 
                   
               
               
                   
               
               
                 CD81 
                 GGNILTPLLQQDCHQKIDELFSGKLYLIGIAAIVVAVIMIFEMILSMVLCCGIRNSSVY 
                  63 
               
               
                 (amino 
                 GGCGGCAACATACTCACCCCCTTACTGCAGCAAGATTGTCATCAGAAAATCGATGAGCTCTTC 
                  64 
               
               
                 acids 
                 TCTGGGAAGCTGTACCTCATTGGAATTGCAGCCATTGTGGTAGCTGTCATTATGATCTTTGAG 
                   
               
               
                 178 to  
                 ATGATTCTGAGCATGGTGCTGTGCTGTGGCATCCGGAACAGCTCCGTGTACTGA 
                   
               
               
                 236) 
                   
                   
               
               
                   
               
               
                 CD81- 
                 MGVEGCTKCIKYLLFVFNFVFWLAGGVILGVALWLRHDPQTTSLLYLELGNKPAPNTFYVGIY 
                 101 
               
               
                 IL-6 
                 ILIAVGAVMMFVGFLGCYGAIQESQCLLGTFFTCLVILFACEVAAGIWGFVNKDQIAKDVKQF 
                   
               
               
                   
                 YDQALQQAVMDDDANNAKAVVKTFHETLNCCGSNALTTLTTTILRNSLCPSGGGGSFPTSQVR 
                   
               
               
                   
                 RGDFTEDTTPNRPVYTTSQVGGLITHVLWEIVEMRKELCNGNSDCMNNDDALAENNLKLPEIQ 
                   
               
               
                   
                 RNDGCYQTGYNQEICLLKISSGLLEYHSYLEYMKNNLKDNKKDKARVLQRDTETLIHIFNQEV 
                   
               
               
                   
                 KDLHKIVLPTPISNALLTDKLESQKEWLRTKTIQFILKSLEEFLKVTLRSTRQTGGGGSGGNI 
                   
               
               
                   
                 LTPLLQQDCHQKIDELFSGKLYLIGIAAIVVAVIMIFEMILSMVLCCGIRNSSVY 
                   
               
               
                   
                 ATGGGGGTGGAGGGCTGCACCAAATGCATCAAATACCTGCTCTTCGTCTTCAATTTCGTCTTC 
                 102 
               
               
                   
                 TGGCTGGCTGGAGGCGTGATCCTAGGTGTAGCTCTGTGGTTGCGTCATGATCCACAGACCACC 
                   
               
               
                   
                 AGCCTGCTGTACCTGGAACTGGGAAACAAACCGGCACCCAACACCTTCTACGTGGGCATCTAC 
                   
               
               
                   
                 ATTCTCATTGCTGTGGGAGCTGTGATGATGTTTGTAGGCTTCCTGGGGTGCTATGGGGCCATC 
                   
               
               
                   
                 CAGGAGTCCCAGTGTCTGCTGGGGACGTTCTTCACCTGCCTTGTGATCCTGTTTGCCTGTGAG 
                   
               
               
                   
                 GTGGCTGCAGGCATCTGGGGCTTCGTAAACAAAGACCAGATCGCCAAGGATGTGAAGCAGTTC 
                   
               
               
                   
                 TATGACCAGGCCCTTCAGCAAGCTGTGATGGATGATGATGCCAACAATGCCAAGGCTGTGGTG 
                   
               
               
                   
                 AAGACTTTCCATGAGACGCTCAACTGTTGTGGCTCCAACGCACTGACCACACTGACTACCACC 
                   
               
               
                   
                 ATACTGAGGAACAGCCTGTGTCCCTCAGGAGGAGGAGGAAGCTTCCCTACTTCACAAGTCCGG 
                   
               
               
                   
                 AGAGGAGACTTCACAGAGGATACCACTCCCAACAGACCTGTCTATACCACTTCACAAGTCGGA 
                   
               
               
                   
                 GGCTTAATTACACATGTTCTCTGGGAAATCGTGGAAATGAGAAAAGAGTTGTGCAATGGCAAT 
                   
               
               
                   
                 TCTGATTGTATGAACAACGATGATGCACTTGCAGAAAACAATCTGAAACTTCCAGAGATACAA 
                   
               
               
                   
                 AGAAATGATGGATGCTACCAAACTGGATATAATCAGGAAATTTGCCTATTGAAAATTTCCTCT 
                   
               
               
                   
                 GGTCTTCTGGAGTACCATAGCTACCTGGAGTACATGAAGAACAACTTAAAAGATAACAAGAAA 
                   
               
               
                   
                 GACAAAGCCAGAGTCCTTCAGAGAGATACAGAAACTCTAATTCATATCTTCAACCAAGAGGTA 
                   
               
               
                   
                 AAAGATTTACATAAAATAGTCCTTCCTACCCCAATTTCCAATGCTCTCCTAACAGATAAGCTG 
                   
               
               
                   
                 GAGTCACAGAAGGAGTGGCTAAGGACCAAGACCATCCAATTCATCTTGAAATCACTTGAAGAA 
                   
               
               
                   
                 TTTCTAAAAGTCACTTTGAGATCTACTCGGCAAACCGGAGGAGGAGGAAGCGGCGGCAACATA 
                   
               
               
                   
                 CTCACCCCCTTACTGCAGCAAGATTGTCATCAGAAAATCGATGAGCTCTTCTCTGGGAAGCTG 
                   
               
               
                   
                 TACCTCATTGGAATTGCAGCCATTGTGGTAGCTGTCATTATGATCTTTGAGATGATTCTGAGC 
                   
               
               
                   
                 ATGGTGCTGTGCTGTGGCATCCGGAACAGCTCCGTGTACTGA 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
             
               
                 TABLE 10 
               
               
                   
               
               
                   
                   
                 SEQ 
               
               
                   
                   
                 ID 
               
               
                   
                 Sequence 
                 NO: 
               
               
                   
               
             
            
               
                 hCD80 
                   MGHTRRQGTSPSKCPYLNFFQLLVLAGLSHFCSG VIHVTKEVKEVATLSCGHNVSVEELAQTR 
                 103 
               
               
                   
                 IYWQKEKKMVLTMMSGDMNIWPEYKNRTIFDITNNLSIVILALRPSDEGTYECVVLKYEKDAF 
                   
               
               
                   
                 KREHLAEVTLSVKADFPTPSISDFEIPTSNIRRIICSTSGGFPEPHLSWLENGEELNAINTTV 
                   
               
               
                   
                 SQDPETELYAVSSKLDFNMTTNHSFMCLIKYGHLRVNQTFNWNTTKQEHFPDNLLPSWAITLI 
                   
               
               
                   
                 SVNGIFVICCLTYCFAPRCRERRRNERLRRESVRPV 
                   
               
               
                   
                 
                   ATGGGCCACACACGGAGGCAGGGAACATCACCATCCAAGTGTCCATACCTCAATTTCTTTCAG 
                 
                 104 
               
               
                   
                   CTCTTGGTGCTGGCTGGTCTTTCTCACTTCTGTTCAGGTGT TATCCACGTGACCAAGGAAGTG 
                   
               
               
                   
                 AAAGAAGTGGCAACGCTGTCCTGTGGTCACAATGTTTCTGTTGAAGAGCTGGCACAAACTCGC 
                   
               
               
                   
                 ATCTACTGGCAAAAGGAGAAGAAAATGGTGCTGACTATGATGTCTGGGGACATGAATATATGG 
                   
               
               
                   
                 CCCGAGTACAAGAACCGGACCATCTTTGATATCACTAATAACCTCTCCATTGTGATCCTGGCT 
                   
               
               
                   
                 CTGCGCCCATCTGACGAGGGCACATACGAGTGTGTTGTTCTGAAGTATGAAAAAGACGCTTTC 
                   
               
               
                   
                 AAGCGGGAACACCTGGCTGAAGTGACGTTATCAGTCAAAGCTGACTTCCCTACACCTAGTATA 
                   
               
               
                   
                 TCTGACTTTGAAATTCCAACTTCTAATATTAGAAGGATAATTTGCTCAACCTCTGGAGGTTTT 
                   
               
               
                   
                 CCAGAGCCTCACCTCTCCTGGTTGGAAAATGGAGAAGAATTAAATGCCATCAACACAACAGTT 
                   
               
               
                   
                 TCCCAAGATCCTGAAACTGAGCTCTATGCTGTTAGCAGCAAACTGGATTTCAATATGACAACC 
                   
               
               
                   
                 AACCACAGCTTCATGTGTCTCATCAAGTATGGACATTTAAGAGTGAATCAGACCTTCAACTGG 
                   
               
               
                   
                 AATACAACCAAGCAAGAGCATTTTCCTGATAACCTGCTCCCATCCTGGGCCATTACCTTAATC 
                   
               
               
                   
                 TCAGTAAATGGAATTTTTGTGATATGCTGCCTGACCTACTGCTTTGCCCCAAGATGCAGAGAG 
                   
               
               
                   
                 AGAAGGAGGAATGAGAGATTGAGAAGGGAAAGTGTACGCCCTGTA 
                   
               
               
                   
               
               
                 hCD9 
                 MPVKGGTKCIKYLLFGFNFIFWLAGIAVLAIGLWLRFDSQTKSIFEQETNNNNSSFYTGVYIL 
                 105 
               
               
                   
                 IGAGALMMLVGFLGCCGAVQESQCMLGLFFGFLLVIFAIEIAAAIWGYSHKDEVIKEVQEFYK 
                   
               
               
                   
                 DTYNKLKTKDEPQRETLKAIHYALNCCGLAGGVEQFISDICPKKDVLETFTVKSCPDAIKEVF 
                   
               
               
                   
                 DNKFHIIGAVGIGIAVVMIFGMIFSMILCCAIRRNREMV 
                   
               
               
                   
                 ATGCCGGTCAAAGGAGGCACCAAGTGCATCAAATACCTGCTGTTCGGATTTAACTTCATCTTC 
                 106 
               
               
                   
                 TGGCTTGCCGGGATTGCTGTCCTTGCCATTGGACTATGGCTCCGATTCGACTCTCAGACCAAG 
                   
               
               
                   
                 AGCATCTTCGAGCAAGAAACTAATAATAATAATTCCAGCTTCTACACAGGAGTCTATATTCTG 
                   
               
               
                   
                 ATCGGAGCCGGCGCCCTCATGATGCTGGTGGGCTTCCTGGGCTGCTGCGGGGCTGTGCAGGAG 
                   
               
               
                   
                 TCCCAGTGCATGCTGGGACTGTTCTTCGGCTTCCTCTTGGTGATATTCGCCATTGAAATAGCT 
                   
               
               
                   
                 GCGGCCATCTGGGGATATTCCCACAAGGATGAGGTGATTAAGGAAGTCCAGGAGTTTTACAAG 
                   
               
               
                   
                 GACACCTACAACAAGCTGAAAACCAAGGATGAGCCCCAGCGGGAAACGCTGAAAGCCATCCAC 
                   
               
               
                   
                 TATGCGTTGAACTGCTGTGGTTTGGCTGGGGGCGTGGAACAGTTTATCTCAGACATCTGCCCC 
                   
               
               
                   
                 AAGAAGGACGTACTCGAAACCTTCACCGTGAAGTCCTGTCCTGATGCCATCAAAGAGGTCTTC 
                   
               
               
                   
                 GACAATAAATTCCACATCATCGGCGCAGTGGGCATCGGCATTGCCGTGGTCATGATATTTGGC 
                   
               
               
                   
                 ATGATCTTCAGTATGATCTTGTGCTGTGCTATCCGCAGGAACCGCGAGATGGTCTAG 
                   
               
               
                   
               
               
                 hCD80- 
                   MGHTRRQGTSPSKCPYLNFFQLLVLAGLSHFCSG VIHVTKEVKEVATLSCGHNVSVEELAQTR 
                 107 
               
               
                 hCD9 
                 IYWQKEKKMVLTMMSGDMNIWPEYKNRTIFDITNNLSIVILALRPSDEGTYECVVLKYEKDAF 
                   
               
               
                   
                 KREHLAEVTLSVKADFPTPSISDFEIPTSNIRRIICSTSGGFPEPHLSWLENGEELNAINTTV 
                   
               
               
                   
                 SQDPETELYAVSSKLDFNMTTNHSFMCLIKYGHLRVNQTFNWNTTKQEHFPDNLLPSWAITLI 
                   
               
               
                   
                 SVNGIFVICCLTYCFAPRCRERRRNERLRRESVRPVMPVKGGTKCIKYLLFGFNFIFWLAGIA 
                   
               
               
                   
                 VLAIGLWLRFDSQTKSIFEQETNNNNSSFYTGVYILIGAGALMMLVGFLGCCGAVQESQCMLG 
                   
               
               
                   
                 LFFGFLLVIFAIEIAAAIWGYSHKDEVIKEVQEFYKDTYNKLKTKDEPQRETLKAIHYALNCC 
                   
               
               
                   
                 GLAGGVEQFISDICPKKDVLETFTVKSCPDAIKEVFDNKFHIIGAVGIGIAVVMIFGMIFSMI 
                   
               
               
                   
                 LCCAIRRNREMV 
                   
               
               
                   
                 
                   ATGGGCCACACACGGAGGCAGGGAACATCACCATCCAAGTGTCCATACCTCAATTTCTTTCAG 
                 
                 108 
               
               
                   
                   CTCTTGGTGCTGGCTGGTCTTTCTCACTTCTGTTCAGGTGT TATCCACGTGACCAAGGAAGTG 
                   
               
               
                   
                 AAAGAAGTGGCAACGCTGTCCTGTGGTCACAATGTTTCTGTTGAAGAGCTGGCACAAACTCGC 
                   
               
               
                   
                 ATCTACTGGCAAAAGGAGAAGAAAATGGTGCTGACTATGATGTCTGGGGACATGAATATATGG 
                   
               
               
                   
                 CCCGAGTACAAGAACCGGACCATCTTTGATATCACTAATAACCTCTCCATTGTGATCCTGGCT 
                   
               
               
                   
                 CTGCGCCCATCTGACGAGGGCACATACGAGTGTGTTGTTCTGAAGTATGAAAAAGACGCTTTC 
                   
               
               
                   
                 AAGCGGGAACACCTGGCTGAAGTGACGTTATCAGTCAAAGCTGACTTCCCTACACCTAGTATA 
                   
               
               
                   
                 TCTGACTTTGAAATTCCAACTTCTAATATTAGAAGGATAATTTGCTCAACCTCTGGAGGTTTT 
                   
               
               
                   
                 CCAGAGCCTCACCTCTCCTGGTTGGAAAATGGAGAAGAATTAAATGCCATCAACACAACAGTT 
                   
               
               
                   
                 TCCCAAGATCCTGAAACTGAGCTCTATGCTGTTAGCAGCAAACTGGATTTCAATATGACAACC 
                   
               
               
                   
                 AACCACAGCTTCATGTGTCTCATCAAGTATGGACATTTAAGAGTGAATCAGACCTTCAACTGG 
                   
               
               
                   
                 AATACAACCAAGCAAGAGCATTTTCCTGATAACCTGCTCCCATCCTGGGCCATTACCTTAATC 
                   
               
               
                   
                 TCAGTAAATGGAATTTTTGTGATATGCTGCCTGACCTACTGCTTTGCCCCAAGATGCAGAGAG 
                   
               
               
                   
                 AGAAGGAGGAATGAGAGATTGAGAAGGGAAAGTGTACGCCCTGTAATGCCGGTCAAAGGAGGC 
                   
               
               
                   
                 ACCAAGTGCATCAAATACCTGCTGTTCGGATTTAACTTCATCTTCTGGCTTGCCGGGATTGCT 
                   
               
               
                   
                 GTCCTTGCCATTGGACTATGGCTCCGATTCGACTCTCAGACCAAGAGCATCTTCGAGCAAGAA 
                   
               
               
                   
                 ACTAATAATAATAATTCCAGCTTCTACACAGGAGTCTATATTCTGATCGGAGCCGGCGCCCTC 
                   
               
               
                   
                 ATGATGCTGGTGGGCTTCCTGGGCTGCTGCGGGGCTGTGCAGGAGTCCCAGTGCATGCTGGGA 
                   
               
               
                   
                 CTGTTCTTCGGCTTCCTCTTGGTGATATTCGCCATTGAAATAGCTGCGGCCATCTGGGGATAT 
                   
               
               
                   
                 TCCCACAAGGATGAGGTGATTAAGGAAGTCCAGGAGTTTTACAAGGACACCTACAACAAGCTG 
                   
               
               
                   
                 AAAACCAAGGATGAGCCCCAGCGGGAAACGCTGAAAGCCATCCACTATGCGTTGAACTGCTGT 
                   
               
               
                   
                 GGTTTGGCTGGGGGCGTGGAACAGTTTATCTCAGACATCTGCCCCAAGAAGGACGTACTCGAA 
                   
               
               
                   
                 ACCTTCACCGTGAAGTCCTGTCCTGATGCCATCAAAGAGGTCTTCGACAATAAATTCCACATC 
                   
               
               
                   
                 ATCGGCGCAGTGGGCATCGGCATTGCCGTGGTCATGATATTTGGCATGATCTTCAGTATGATC 
                   
               
               
                   
                 TTGTGCTGTGCTATCCGCAGGAACCGCGAGATGGTCTAG 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
             
               
                 TABLE 11 
               
               
                   
               
               
                   
                   
                 SEQ 
               
               
                   
                   
                 ID 
               
               
                   
                 Sequence 
                 NO: 
               
               
                   
               
             
            
               
                 hIL-2 
                 APTSSSTKKTQLQLEHLLLDLQMILNGINNYKNPKLTRMLTFKFYMPKKATELKHLQCLEEEL 
                 109 
               
               
                 (from 
                 KPLEEVLNLAQSKNFHLRPRDLISNINVIVLELKGSETTFMCEYADETATIVEFLNRWITFCQ 
                   
               
               
                 which 
                 SIISTLT 
                   
               
               
                 signal 
                 GCACCTACTTCAAGTTCTACAAAGAAAACACAGCTACAACTGGAGCATTTACTGCTGGATTTA 
                 110 
               
               
                 peptide  
                 CAGATGATTTTGAATGGAATTAATAATTACAAGAATCCCAAACTCACCAGGATGCTCACATTT 
                   
               
               
                 is 
                 AAGTTTTACATGCCCAAGAAGGCCACAGAACTGAAACATCTTCAGTGTCTAGAAGAAGAACTC 
                   
               
               
                 removed)  
                 AAACCTCTGGAGGAAGTGCTAAATTTAGCTCAAAGCAAAAACTTTCACTTAAGACCCAGGGAC 
                   
               
               
                   
                 TTAATCAGCAATATCAACGTAATAGTTCTGGAACTAAAGGGATCTGAAACAACATTCATGTGT 
                   
               
               
                   
                 GAATATGCTGATGAGACAGCAACCATTGTAGAATTTCTGAACAGATGGATTACCTTTTGTCAA 
                   
               
               
                   
                 AGCATCATCTCAACACTGACT 
                   
               
               
                   
               
               
                 hCD63 
                 MAVEGGMKCVKFLLYVLLLAFCACAVGLIAVGVGAQLVLSQTIIQGATPGSLLPVVIIAVGVF 
                 111 
               
               
                 (amino 
                 LFLVAFVGCCGACKENYCLMITFAIFLSLIMLVEVAAAIAGYVFRDKVMSEFNNNFRQQMENY 
                   
               
               
                 acids 
                 PKNNHTASILDRMQADFKCCGAANYTDWEKIPSMSKNRVPDSCC 
                   
               
               
                 1 to 
                 ATGGCGGTGGAAGGAGGAATGAAATGTGTGAAGTTCTTGCTCTACGTCCTCCTGCTGGCCTTT 
                 112 
               
               
                 170) 
                 TGCGCCTGTGCAGTGGGACTGATTGCCGTGGGTGTCGGGGCACAGCTTGTCCTGAGTCAGACC 
                   
               
               
                   
                 ATAATCCAGGGGGCTACCCCTGGCTCTCTGTTGCCAGTGGTCATCATCGCAGTGGGTGTCTTC 
                   
               
               
                   
                 CTCTTCCTGGTGGCTTTTGTGGGCTGCTGCGGGGCCTGCAAGGAGAACTATTGTCTTATGATC 
                   
               
               
                   
                 ACGTTTGCCATCTTTCTGTCTCTTATCATGTTGGTGGAGGTGGCCGCAGCCATTGCTGGCTAT 
                   
               
               
                   
                 GTGTTTAGAGATAAGGTGATGTCAGAGTTTAATAACAACTTCCGGCAGCAGATGGAGAATTAC 
                   
               
               
                   
                 CCGAAAAACAACCACACTGCTTCGATCCTGGACAGGATGCAGGCAGATTTTAAGTGCTGTGGG 
                   
               
               
                   
                 GCTGCTAACTACACAGATTGGGAGAAAATCCCTTCCATGTCGAAGAACCGAGTCCCCGACTCC 
                   
               
               
                   
                 TGCTGC 
                   
               
               
                   
               
               
                 hCD63 
                 INVTVGCGINFNEKAIHKEGCVEKIGGWLRKNVLVVAAAALGIAFVEVLGIVFACCLVKSIRS 
                 113 
               
               
                 (amino 
                 GYEVM 
                   
               
               
                 acids 
                 ATTAATGTTACTGTGGGCTGTGGGATTAATTTCAACGAGAAGGCGATCCATAAGGAGGGCTGT 
                 114 
               
               
                 171 to  
                 GTGGAGAAGATTGGGGGCTGGCTGAGGAAAAATGTGCTGGTGGTAGCTGCAGCAGCCCTTGGA 
                   
               
               
                 238) 
                 ATTGCTTTTGTCGAGGTTTTGGGAATTGTCTTTGCCTGCTGCCTCGTGAAGAGTATCAGAAGT 
                   
               
               
                   
                 GGCTACGAGGTGATGTAG 
                   
               
               
                   
               
               
                 hCD63- 
                 MAVEGGMKCVKFLLYVLLLAFCACAVGLIAVGVGAQLVLSQTIIQGATPGSLLPVVIIAVGVF 
                 115 
               
               
                 IL-2 
                 LFLVAFVGCCGACKENYCLMITFAIFLSLIMLVEVAAAIAGYVFRDKVMSEFNNNFRQQMENY 
                   
               
               
                   
                 PKNNHTASILDRM8ADFKCCGAANYTDWEKIPSMSKNRVPDSCCGGGGSAPTSSSTKKTQLQL 
                   
               
               
                   
                 EHLLLDLQMILNGINNYKNPKLTRMLTFKFYMPKKATELKHLQCLEEELKPLEEVLNLAQSKN 
                   
               
               
                   
                 FHLRPRDLISNINVIVLELKGSETTFMCEYADETATIVEFLNRWITFCQSIISTLTGGGGSIN 
                   
               
               
                   
                 VTVGCGINFNEKAIHKEGCVEKIGGWLRKNVLVVAAAALGIAFVEVLGIVFACCLVKSIRSGY 
                   
               
               
                   
                 EVM 
                   
               
               
                   
                 ATGGCGGTGGAAGGAGGAATGAAATGTGTGAAGTTCTTGCTCTACGTCCTCCTGCTGGCCTTT 
                 116 
               
               
                   
                 TGCGCCTGTGCAGTGGGACTGATTGCCGTGGGTGTCGGGGCACAGCTTGTCCTGAGTCAGACC 
                   
               
               
                   
                 ATAATCCAGGGGGCTACCCCTGGCTCTCTGTTGCCAGTGGTCATCATCGCAGTGGGTGTCTTC 
                   
               
               
                   
                 CTCTTCCTGGTGGCTTTTGTGGGCTGCTGCGGGGCCTGCAAGGAGAACTATTGTCTTATGATC 
                   
               
               
                   
                 ACGTTTGCCATCTTTCTGTCTCTTATCATGTTGGTGGAGGTGGCCGCAGCCATTGCTGGCTAT 
                   
               
               
                   
                 GTGTTTAGAGATAAGGTGATGTCAGAGTTTAATAACAACTTCCGGCAGCAGATGGAGAATTAC 
                   
               
               
                   
                 CCGAAAAACAACCACACTGCTTCGATCCTGGACAGGATGCAGGCAGATTTTAAGTGCTGTGGG 
                   
               
               
                   
                 GCTGCTAACTACACAGATTGGGAGAAAATCCCTTCCATGTCGAAGAACCGAGTCCCCGACTCC 
                   
               
               
                   
                 TGCTGCGGAGGAGGAGGAAGCGCACCTACTTCAAGTTCTACAAAGAAAACACAGCTACAACTG 
                   
               
               
                   
                 GAGCATTTACTGCTGGATTTACAGATGATTTTGAATGGAATTAATAATTACAAGAATCCCAAA 
                   
               
               
                   
                 CTCACCAGGATGCTCACATTTAAGTTTTACATGCCCAAGAAGGCCACAGAACTGAAACATCTT 
                   
               
               
                   
                 CAGTGTCTAGAAGAAGAACTCAAACCTCTGGAGGAAGTGCTAAATTTAGCTCAAAGCAAAAAC 
                   
               
               
                   
                 TTTCACTTAAGACCCAGGGACTTAATCAGCAATATCAACGTAATAGTTCTGGAACTAAAGGGA 
                   
               
               
                   
                 TCTGAAACAACATTCATGTGTGAATATGCTGATGAGACAGCAACCATTGTAGAATTTCTGAAC 
                   
               
               
                   
                 AGATGGATTACCTTTTGTCAAAGCATCATCTCAACACTGACTGGAGGAGGAGGAAGCATTAAT 
                   
               
               
                   
                 GTTACTGTGGGCTGTGGGATTAATTTCAACGAGAAGGCGATCCATAAGGAGGGCTGTGTGGAG 
                   
               
               
                   
                 AAGATTGGGGGCTGGCTGAGGAAAAATGTGCTGGTGGTAGCTGCAGCAGCCCTTGGAATTGCT 
                   
               
               
                   
                 TTTGTCGAGGTTTTGGGAATTGTCTTTGCCTGCTGCCTCGTGAAGAGTATCAGAAGTGGCTAC 
                   
               
               
                   
                 GAGGTGATGTAG 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
             
               
                 TABLE 12 
               
               
                   
               
               
                   
                   
                 SEQ 
               
               
                   
                   
                 ID  
               
               
                   
                 Sequence 
                 NO: 
               
               
                   
               
             
            
               
                 Signal  
                 
                   MSRSVALAVLALLSLSGLEA 
                 
                 117 
               
               
                 peptide 
                 
                   ATGTCTCGCTCCGTGGCCTTAGCTGTGCTCGCGCTACTCTCTCTTTCTGGCCTGGAGGCT 
                 
                 118 
               
               
                 of hβ 2   
                   
                   
               
               
                 micro- 
                   
                   
               
               
                 globulin 
                   
                   
               
               
                   
               
               
                 WT1  
                 CYTWNQMNL 
                 119 
               
               
                 peptide  
                 TGCTACACCTGGAACCAGATGAACCTG 
                 120 
               
               
                 1 (for 
                   
                   
               
               
                 MHC class 
                   
                   
               
               
                 I  
                   
                   
               
               
                 molecule) 
                   
                   
               
               
                   
               
               
                 Peptide  
                 GGGASGGGGSGGGGS 
                   5 
               
               
                 linker 1 
                 GGCGGAGGTGCCTCTGGCGGTGGGGGCAGCGGTGGAGGGGGCAGT 
                   6 
               
               
                   
               
               
                 hβ 2   
                 IQRTPKIQVYSRHPAENGKSNFLNCYVSGFHPSDIEVDLLKNGERIEKVEHSDLSFSKDWSFY 
                 121 
               
               
                 Micro-  
                 LLYYTEFTPTEKDEYACRVNHVTLSQPKIVKWDRDM 
                   
               
               
                 globulin 
                 ATCCAGCGTACTCCAAAGATTCAGGTTTACTCACGTCATCCAGCAGAGAATGGAAAGTCAAAT 
                 122 
               
               
                 (from 
                 TTCCTGAATTGCTATGTGTCTGGGTTTCATCCATCCGACATTGAAGTTGACTTACTGAAGAAT 
                   
               
               
                 which 
                 GGAGAGAGAATTGAAAAAGTGGAGCATTCAGACTTGTCTTTCAGCAAGGACTGGTCTTTCTAT 
                   
               
               
                 signal  
                 CTCTTGTACTACACTGAATTCACCCCCACTGAAAAAGATGAGTATGCCTGCCGTGTGAACCAT 
                   
               
               
                 peptide 
                 GTGACTTTGTCACAGCCCAAGATAGTTAAGTGGGATCGAGACATG 
                   
               
               
                 is  
                   
                   
               
               
                 removed) 
                   
                   
               
               
                   
               
               
                 hMHC  
                 GSHSMRYFSTSVSRPGRGEPRFIAVGYVDDTQFVRFDSDAASQRMEPRAPWIEQEGPEYWDEE 
                 123 
               
               
                 class 
                 TGKVKAHSQTDRENLRIALRYYNQSEAGSHTLQMMFGCDVGSDGRFLRGYHQYAYDGKDYIAL 
                   
               
               
                 Iα chain 
                 KEDLRSWTAADMAAQITKRKWEAAHVAEQQRAYLEGTCVDGLRRYLENGKETLQRTDPPKTHM 
                   
               
               
                 (from 
                 THHPISDHEATLRCWALGFYPAEITLTWQRDGEDQTQDTELVETRPAGDGTFQKWAAVVVPSG 
                   
               
               
                 which 
                 EEQRYTCHVQHEGLPKPLTLRWEPSSQPTVPIVGIIAGLVLLGAVITGAVVAAVMWRRNSSDR 
                   
               
               
                 signal  
                 KGGSYSQAASSDSAQGSDVSLTACKV 
                   
               
               
                 peptide  
                 GGCTCCCACTCCATGAGGTATTTCTCCACATCCGTGTCCCGGCCCGGCCGCGGGGAGCCCCGC 
                 124 
               
               
                 is  
                 TTCATCGCCGTGGGCTACGTGGACGACACGCAGTTCGTGCGGTTCGACAGCGACGCCGCGAGC 
                   
               
               
                 removed) 
                 CAGAGGATGGAGCCGCGGGCGCCGTGGATAGAGCAGGAGGGGCCGGAGTATTGGGACGAGGAG 
                   
               
               
                   
                 ACAGGGAAAGTGAAGGCCCACTCACAGACTGACCGAGAGAACCTGCGGATCGCGCTCCGCTAC 
                   
               
               
                   
                 TACAACCAGAGCGAGGCCGGTTCTCACACCCTCCAGATGATGTTTGGCTGCGACGTGGGGTCG 
                   
               
               
                   
                 GACGGGCGCTTCCTCCGCGGGTACCACCAGTACGCCTACGACGGCAAGGATTACATCGCCCTG 
                   
               
               
                   
                 AAAGAGGACCTGCGCTCTTGGACCGCGGCGGACATGGCGGCTCAGATCACCAAGCGCAAGTGG 
                   
               
               
                   
                 GAGGCGGCCCATGTGGCGGAGCAGCAGAGAGCCTACCTGGAGGGCACGTGCGTGGACGGGCTC 
                   
               
               
                   
                 CGCAGATACCTGGAGAACGGGAAGGAGACGCTGCAGCGCACGGACCCCCCCAAGACACATATG 
                   
               
               
                   
                 ACCCACCACCCCATCTCTGACCATGAGGCCACTCTGAGATGCTGGGCCCTGGGCTTCTACCCT 
                   
               
               
                   
                 GCGGAGATCACACTGACCTGGCAGCGGGATGGGGAGGACCAGACCCAGGACACGGAGCTTGTG 
                   
               
               
                   
                 GAGACCAGGCCTGCAGGGGATGGAACCTTCCAGAAGTGGGCAGCTGTGGTGGTACCTTCTGGA 
                   
               
               
                   
                 GAGGAGCAGAGATACACCTGCCATGTGCAGCATGAGGGTCTGCCCAAGCCCCTCACCCTGAGA 
                   
               
               
                   
                 TGGGAGCCATCTTCCCAGCCCACCGTCCCCATCGTGGGCATCATTGCTGGCCTGGTTCTCCTT 
                   
               
               
                   
                 GGAGCTGTGATCACTGGAGCTGTGGTCGCTGCTGTGATGTGGAGGAGGAACAGCTCAGATAGA 
                   
               
               
                   
                 AAAGGAGGGAGCTACTCTCAGGCTGCAAGCAGTGACAGTGtCCAGGGCTCTGATGTGTCTCTC 
                   
               
               
                   
                 ACAGCTTGTAAAGTG 
                   
               
               
                   
               
               
                 Peptide 
                 GGGGSGGGGSGGGGSGGGGS 
                  11 
               
               
                 linker 2 
                 GGGGGGGGAGGCTCCGGTGGAGGGGGGTCTGGAGGGGGGGGGTCTGGTGGAGGCGGAAGT 
                  12 
               
               
                   
               
               
                 h Single 
                 IQRTPKIQVYSRHPAENGKSNFLNCYVSGFHPSDIEVDLLKNGERIEKVEHSDLSFSKDWSFY 
                 125 
               
               
                 chain 
                 LLYYTEFTPTEKDEYACRVNHVTLSQPKIVKWDRDMGGGGSGGGGSGGGGSGGGGSGSHSMRY 
                   
               
               
                 MHC class  
                 FSTSVSRPGRGEPRFIAVGYVDDTQFVRFDSDAASQRMEPRAPWIEQEGPEYWDEETGKVKAH 
                   
               
               
                 I mole- 
                 SQTDRENLRIALRYYNQSEAGSHTLQMMFGCDVGSDGRFLRGYHQYAYDGKDYIALKEDLRSW 
                   
               
               
                 cule (β 2   
                 TAADMAAQITKRKWEAAHVAEQQRAYLEGTCVDGLRRYLENGKETLQRTDPPKTHMTHHPISD 
                   
               
               
                 micro- 
                 HEATLRCWALGFYPAEITLTWQRDGEDQTQDTELVETRPAGDGTFQKWAAVVVPSGEEQRYTC 
                   
               
               
                 globulin 
                 HVQHEGLPKPLTLRWEPSSQPTVPIVGIIAGLVLLGAVITGAVVAAVMWRRNSSDRKGGSYSQ 
                   
               
               
                 (from 
                 AASSDSAQGSDVSLTACKV 
                   
               
               
                 which 
                 ATCCAGCGTACTCCAAAGATTCAGGTTTACTCACGTCATCCAGCAGAGAATGGAAAGTCAAAT 
                 126 
               
               
                 signal 
                 TTCCTGAATTGCTATGTGTCTGGGTTTCATCCATCCGACATTGAAGTTGACTTACTGAAGAAT 
                   
               
               
                 peptide 
                 GGAGAGAGAATTGAAAAAGTGGAGCATTCAGACTTGTCTTTCAGCAAGGACTGGTCTTTCTAT 
                   
               
               
                 is re- 
                 CTCTTGTACTACACTGAATTCACCCCCACTGAAAAAGATGAGTATGCCTGCCGTGTGAACCAT 
                   
               
               
                 moved) + 
                 GTGACTTTGTCACAGCCCAAGATAGTTAAGTGGGATCGAGACATGGGGGGGGGAGGCTCCGGT 
                   
               
               
                 peptide 
                 GGAGGGGGGTCTGGAGGGGGGGGGTCTGGTGGAGGCGGAAGTGGCTCCCACTCCATGAGGTAT 
                   
               
               
                 linker 
                 TTCTCCACATCCGTGTCCCGGCCCGGCCGCGGGGAGCCCCGCTTCATCGCCGTGGGCTACGTG 
                   
               
               
                 2 + MHC 
                 GACGACACGCAGTTCGTGCGGTTCGACAGCGACGCCGCGAGCCAGAGGATGGAGCCGCGGGCG 
                   
               
               
                 class 
                 CCGTGGATAGAGCAGGAGGGGCCGGAGTATTGGGACGAGGAGACAGGGAAAGTGAAGGCCCAC 
                   
               
               
                 Iα chain 
                 TCACAGACTGACCGAGAGAACCTGCGGATCGCGCTCCGCTACTACAACCAGAGCGAGGCCGGT 
                   
               
               
                 (from  
                 TCTCACACCCTCCAGATGATGTTTGGCTGCGACGTGGGGTCGGACGGGCGCTTCCTCCGCGGG 
                   
               
               
                 which 
                 TACCACCAGTACGCCTACGACGGCAAGGATTACATCGCCCTGAAAGAGGACCTGCGCTCTTGG 
                   
               
               
                 signal  
                 ACCGCGGCGGACATGGCGGCTCAGATCACCAAGCGCAAGTGGGAGGCGGCCCATGTGGCGGAG 
                   
               
               
                 peptide 
                 CAGCAGAGAGCCTACCTGGAGGGCACGTGCGTGGACGGGCTCCGCAGATACCTGGAGAACGGG 
                   
               
               
                 is 
                 AAGGAGACGCTGCAGCGCACGGACCCCCCCAAGACACATATGACCCACCACCCCATCTCTGAC 
                   
               
               
                 removed)) 
                 CATGAGGCCACTCTGAGATGCTGGGCCCTGGGCTTCTACCCTGCGGAGATCACACTGACCTGG 
                   
               
               
                   
                 CAGCGGGATGGGGAGGACCAGACCCAGGACACGGAGCTTGTGGAGACCAGGCCTGCAGGGGAT 
                   
               
               
                   
                 GGAACCTTCCAGAAGTGGGCAGCTGTGGTGGTACCTTCTGGAGAGGAGCAGAGATACACCTGC 
                   
               
               
                   
                 CATGTGCAGCATGAGGGTCTGCCCAAGCCCCTCACCCTGAGATGGGAGCCATCTTCCCAGCCC 
                   
               
               
                   
                 ACCGTCCCCATCGTGGGCATCATTGCTGGCCTGGTTCTCCTTGGAGCTGTGATCACTGGAGCT 
                   
               
               
                   
                 GTGGTCGCTGCTGTGATGTGGAGGAGGAACAGCTCAGATAGAAAAGGAGGGAGCTACTCTCAG 
                   
               
               
                   
                 GCTGCAAGCAGTGACAGTGCCCAGGGCTCTGATGTGTCTCTCACAGCTTGTAAAGTG 
                   
               
               
                   
               
               
                 hsc-  
                   MSRSVALAVLALLSLSGLEA CYTWNQMNLGGGASGGGGSGGGGSIQRTPKIQVYSRHPAENGK 
                 127 
               
               
                 Trimer 
                 SNFLNCYVSGFHPSDIEVDLLKNGERIEKVEHSDLSFSKDWSFYLLYYTEFTPTEKDEYACRV 
                   
               
               
                 (WT1 
                 NHVTLSQPKIVKWDRDMGGGGSGGGGSGGGGSGGGGSGSHSMRYFSTSVSRPGRGEPRFIAVG 
                   
               
               
                 peptide 
                 YVDDTQFVRFDSDAASQRMEPRAPWIEQEGPEYWDEETGKVKAHSQTDRENLRIALRYYNQSE 
                   
               
               
                 1 + 
                 AGSHTLQMMFGCDVGSDGRFLRGYHQYAYDGKDYIALKEDLRSWTAADMAAQITKRKWEAAHV 
                   
               
               
                 peptide 
                 AEQQRAYLEGTCVDGLRRYLENGKETLQRTDPPKTHMTHHPISDHEATLRCWALGFYPAEITL 
                   
               
               
                 linker  
                 TWQRDGEDQTQDTELVETRPAGDGTFQKWAAVVVPSGEEQRYTCHVQHEGLPKPLTLRWEPSS 
                   
               
               
                 1 +   
                 QPTVPIVGIIAGLVLLGAVITGAVVAAVMWRRNSSDRKGGSYSQAASSDSAQGSDVSLTACKV 
                   
               
               
                 single 
                   ATGTCTCGCTCCGTGGCCTTAGCTGTGCTCGCGCTACTCTCTCTTTCTGGCCTGGAGGCT TGC 
                 128 
               
               
                 chain   
                 TACACCTGGAACCAGATGAACCTGGGCGGAGGTGCCTCTGGCGGTGGGGGCAGCGGTGGAGGG 
                   
               
               
                 MHC  
                 GGCAGTATCCAGCGTACTCCAAAGATTCAGGTTTACTCACGTCATCCAGCAGAGAATGGAAAG 
                   
               
               
                 class 
                 TCAAATTTCCTGAATTGCTATGTGTCTGGGTTTCATCCATCCGACATTGAAGTTGACTTACTG 
                   
               
               
                 I  
                 AAGAATGGAGAGAGAATTGAAAAAGTGGAGCATrCAGACTTGTCTTTCAGCAAGGACTGGTCT 
                   
               
               
                 molecule) 
                 TTCTATCTCTTGTACTACACTGAATTCACCCCCACTGAAAAAGATGAGTATGCCTGCCGTGTG 
                   
               
               
                   
                 AACCATGTGACTTTGTCACAGCCCAAGATAGTTAAGTGGGATCGAGACATGGGGGGGGGAGGC 
                   
               
               
                   
                 TCCGGTGGAGGGGGGTCTGGAGGGGGGGGGTCTGGTGGAGGCGGAAGTGGCTCCCACTCCATG 
                   
               
               
                   
                 AGGTATTTCTCCACATCCGTGTCCCGGCCCGGCCGCGGGGAGCCCCGCTTCATCGCCGTGGGC 
                   
               
               
                   
                 TACGTGGACGACACGCAGTTCGTGCGGTTCGACAGCGACGCCGCGAGCCAGAGGATGGAGCCG 
                   
               
               
                   
                 CGGGCGCCGTGGATAGAGCAGGAGGGGCCGGAGTATTGGGACGAGGAGACAGGGAAAGTGAAG 
                   
               
               
                   
                 GCCCACTCACAGACTGACCGAGAGAACCTGCGGATCGCGCTCCGCTACTACAACCAGAGCGAG 
                   
               
               
                   
                 GCCGGTTCTCACACCCTCCAGATGATGTTTGGCTGCGACGTGGGGTCGGACGGGCGCTTCCTC 
                   
               
               
                   
                 CGCGGGTACCACCAGTACGCCTACGACGGCAAGGATTACATCGCCCTGAAAGAGGACCTGCGC 
                   
               
               
                   
                 TCTTGGACCGCGGCGGACATGGCGGCTCAGATCACCAAGCGCAAGTGGGAGGCGGCCCATGTG 
                   
               
               
                   
                 GCGGAGCAGCAGAGAGCCTACCTGGAGGGCACGTGCGTGGACGGGCTCCGCAGATACCTGGAG 
                   
               
               
                   
                 AACGGGAAGGAGACGCTGCAGCGCACGGACCCCCCCAAGACACATATGACCCACCACCCCATC 
                   
               
               
                   
                 TCTGACCATGAGGCCACTCTGAGATGCTGGGCCCTGGGCTTCTACCCTGCGGAGATCACACTG 
                   
               
               
                   
                 ACCTGGCAGCGGGATGGGGAGGACCAGACCCAGGACACGGAGCTTGTGGAGACCAGGCCTGCA 
                   
               
               
                   
                 GGGGATGGAACCTTCCAGAAGTGGGCAGCTGTGGTGGTACCTTCTGGAGAGGAGCAGAGATAC 
                   
               
               
                   
                 ACCTGCCATGTGCAGCATGAGGGTCTGCCCAAGCCCCTCACCCTGAGATGGGAGCCATCTTCC 
                   
               
               
                   
                 CAGCCCACCGTCCCCATCGTGGGCATCATTGCTGGCCTGGTTCTCCTTGGAGCTGTGATCACT 
                   
               
               
                   
                 GGAGCTGTGGTCGCTGCTGTGATGTGGAGGAGGAACAGCTCAGATAGAAAAGGAGGGAGCTAC 
                   
               
               
                   
                 TCTCAGGCTGCAAGCAGTGACAGTGCCCAGGGCTCTGATGTGTCTCTCACAGCTTGTAAAGTG 
                   
               
               
                   
               
               
                 hCD81 
                 MGVEGCTKCIKYLLFVFNFVFWLAGGVILGVALWLRHDPQTTNLLYLELGDKPAPNTFYVGIY 
                 129 
               
               
                   
                 ILIAVGAVMMFVGFLGCYGAIQESQCLLGTFFTCLVILFACEVAAGIWGFVNKDQIAKDVKQF 
                   
               
               
                   
                 YDQALQQAVVDDDANNAKAVVKTFHETLDCCGSSTLTALTTSVLKNNLCPSGSNIISNLFKED 
                   
               
               
                   
                 CHQKIDDLFSGKLYLIGIAAIVVAVIMIFEMILSMVLCCGIRNSSVY 
                   
               
               
                   
                 ATGGGAGTGGAGGGCTGCACCAAGTGCATCAAGTACCTGCTCTTCGTCTTCAATTTCGTCTTC 
                 130 
               
               
                   
                 TGGCTGGCTGGAGGCGTGATCCTGGGTGTGGCCCTGTGGCTCCGCCATGACCCGCAGACCACC 
                   
               
               
                   
                 AACCTCCTGTATCTGGAGCTGGGAGACAAGCCCGCGCCCAACACCTTCTATGTAGGCATCTAC 
                   
               
               
                   
                 ATCCTCATCGCTGTGGGCGCTGTCATGATGTTCGTTGGCTTCCTGGGCTGCTACGGGGCCATC 
                   
               
               
                   
                 CAGGAATCCCAGTGCCTGCTGGGGACGTTCTTCACCTGCCTGGTCATCCTGTTTGCCTGTGAG 
                   
               
               
                   
                 GTGGCCGCCGGCATCTGGGGCTTTGTCAACAAGGACCAGATCGCCAAGGATGTGAAGCAGTTC 
                   
               
               
                   
                 TATGACCAGGCCCTACAGCAGGCCGTGGTGGATGATGACGCCAACAACGCCAAGGCTGTGGTG 
                   
               
               
                   
                 AAGACCTTCCACGAGACGCTTGACTGCTGTGGCTCCAGCACACTGACTGCTTTGACCACCTCA 
                   
               
               
                   
                 GTGCTCAAGAACAATTTGTGTCCCTCGGGCAGCAACATCATCAGCAACCTCTTCAAGGAGGAC 
                   
               
               
                   
                 TGCCACCAGAAGATCGATGACCTCTTCTCCGGGAAGCTGTACCTCATCGGCATTGCTGCCATC 
                   
               
               
                   
                 GTGGTCGCTGTGATCATGATCTTCGAGATGATCCTGAGCATGGTGCTGTGCTGTGGCATCCGG 
                   
               
               
                   
                 AACAGCTCCGTGTACTGA 
                   
               
               
                   
               
               
                 hsc- 
                   MSRSVALAVLALLSLSGLEA CYTWNQMNLGGGASGGGGSGGGGSIQRTPKIQVYSRHPAENGK 
                 131 
               
               
                 Trimer- 
                 SNFLNCYVSGFHPSDIEVDLLKNGERIEKVEHSDLSFSKDWSFYLLYYTEFTPTEKDEYACRV 
                   
               
               
                 CD81 
                 NHVTLSQPKIVKWDRDMGGGGSGGGGSGGGGSGGGGSGSHSMRYFSTSVSRPGRGEPRFIAVG 
                   
               
               
                 (sc- 
                 YVDDTQFVRFDSDAASQRMEPRAPWIEQEGPEYWDEETGKVKAHSQTDRENLRIALRYYNQSE 
                   
               
               
                 Trimer + 
                 AGSHTLQMMFGCDVGSDGRFLRGYHQYAYDGKDYIALKEDLRSWTAADMAAQITKRKWEAAHV 
                   
               
               
                 CD81) 
                 AEQQRAYLEGTCVDGLRRYLENGKETLQRTDPPKTHMTHHPISDHEATLRCWALGFYPAEITL 
                   
               
               
                   
                 TWQRDGEDQTQDTELVETRPAGDGTFQKWAAVVVPSGEEQRYTCHVQHEGLPKPLTLRWEPSS 
                   
               
               
                   
                 QPTVPIVGIIAGLVLLGAVITGAVVAAVMWRRNSSDRKGGSYSQAASSDSAQGSDVSLTACKV 
                   
               
               
                   
                 MGVEGCTKCIKYLLFVFNFVFWLAGGVILGVALWLRHDPQTTNLLYLELGDKPAPNTFYVGIY 
                   
               
               
                   
                 ILIAVGAVMMFVGFLGCYGAIQESQCLLGTFFTCLVILFACEVAAGIWGFVNKDQIAKDVKQF 
                   
               
               
                   
                 YDQALQQAYVDDDANNAKAVVKTFHETLDCCGSSTLTALTTSVLKNNLCPSGSNIISNLFKED 
                   
               
               
                   
                 CHQKIDDLFSGKLYLIGIAAIVVAVIMIFEMILSMVLCCGIRNSSVY 
                   
               
               
                   
                   ATGTCTCGCTCCGTGGCCTTAGCTGTGCTCGCGCTACTCTCTCTTTCTGGCCTGGAGGCT TGC 
                 132 
               
               
                   
                 TACACCTGGAACCAGATGAACCTGGGCGGAGGTGCCTCTGGCGGTGGGGGCAGCGGTGGAGGG 
                   
               
               
                   
                 GGCAGTATCCAGCGTACTCCAAAGATTCAGGTTTACTCACGTCATCCAGCAGAGAATGGAAAG 
                   
               
               
                   
                 TCAAATTTCCTGAATTGCTATGTGTCTGGGTTTCATCCATCCGACATTGAAGTTGACTTACTG 
                   
               
               
                   
                 AAGAATGGAGAGAGAATTGAAAAAGTGGAGCATTCAGACTTGTCTTTCAGCAAGGACTGGTCT 
                   
               
               
                   
                 TTCTATCTCTTGTACTACACTGAATTCACCCCCACTGAAAAAGATGAGTATGCCTGCCGTGTG 
                   
               
               
                   
                 AACCATGTGACTTTGTCACAGCCCAAGATAGTTAAGTGGGATCGAGACATGGGGGGGGGAGGC 
                   
               
               
                   
                 TCCGGTGGAGGGGGGTCTGGAGGGGGGGGGTCTGGTGGAGGCGGAAGTGGCTCCCACTCCATG 
                   
               
               
                   
                 AGGTATTTCTCCACATCCGTGTCCCGGCCCGGCCGCGGGGAGCCCCGCTTCATCGCCGTGGGC 
                   
               
               
                   
                 TACGTGGACGACACGCAGTTCGTGCGGTTCGACAGCGACGCCGCGAGCCAGAGGATGGAGCCG 
                   
               
               
                   
                 CGGGCGCCGTGGATAGAGCAGGAGGGGCCGGAGTATTGGGACGAGGAGACAGGGAAAGTGAAG 
                   
               
               
                   
                 GCCCACTCACAGACTGACCGAGAGAACCTGCGGATCGCGCTCCGCTACTACAACCAGAGCGAG 
                   
               
               
                   
                 GCCGGTTCTCACACCCTCCAGATGATGTTTGGCTGCGACGTGGGGTCGGACGGGCGCTTCCTC 
                   
               
               
                   
                 CGCGGGTACCACCAGTACGCCTACGACGGCAAGGATTACATCGCCCTGAAAGAGGACCTGCGC 
                   
               
               
                   
                 TCTTGGACCGCGGCGGACATGGCGGCTCAGATCACCAAGCGCAAGTGGGAGGCGGCCCATGTG 
                   
               
               
                   
                 GCGGAGCAGCAGAGAGCCTACCTGGAGGGCACGTGCGTGGACGGGCTCCGCAGATACCTGGAG 
                   
               
               
                   
                 AACGGGAAGGAGACGCTGCAGCGCACGGACCCCCCCAAGACACATATGACCCACCACCCCATC 
                   
               
               
                   
                 TCTGACCATGAGGCCACTCTGAGATGCTGGGCCCTGGGCTTCTACCCTGCGGAGATCACACTG 
                   
               
               
                   
                 ACCTGGCAGCGGGATGGGGAGGACCAGACCCAGGACACGGAGCTTGTGGAGACCAGGCCTGCA 
                   
               
               
                   
                 GGGGATGGAACCTTCCAGAAGTGGGCAGCTGTGGTGGTACCTTCTGGAGAGGAGCAGAGATAC 
                   
               
               
                   
                 ACCTGCCATGTGCAGCATGAGGGTCTGCCCAAGCCCCTCACCCTGAGATGGGAGCCATCTTCC 
                   
               
               
                   
                 CAGCCCACCGTCCCCATCGTGGGCATCATTGCTGGCCTGGTTCTCCTTGGAGCTGTGATCACT 
                   
               
               
                   
                 GGAGCTGTGGTCGCTGCTGTGATGTGGAGGAGGAACAGCTCAGATAGAAAAGGAGGGAGCTAC 
                   
               
               
                   
                 TCTCAGGCTGCAAGCAGTGACAGTGCCCAGGGCTCTGATGTGTCTCTCACAGCTTGTAAAGTG 
                   
               
               
                   
                 ATGGGAGTGGAGGGCTGCACCAAGTGCATCAAGTACCTGCTCTTCGTCTTCAATTTCGTCTTC 
                   
               
               
                   
                 TGGCTGGCTGGAGGCGTGATCCTGGGTGTGGCCCTGTGGCTCCGCCATGACCCGCAGACCACC 
                   
               
               
                   
                 AACCTCCTGTATCTGGAGCTGGGAGACAAGCCCGCGCCCAACACCTTCTATGTAGGCATCTAC 
                   
               
               
                   
                 ATCCTCATCGCTGTGGGCGCTGTCATGATGTTCGTTGGCTTCCTGGGCTGCTACGGGGCCATC 
                   
               
               
                   
                 CAGGAATCCCAGTGCCTGCTGGGGACGTTCTTCACCTGCCTGGTCATCCTGTTTGCCTGTGAG 
                   
               
               
                   
                 GTGGCCGCCGGCATCTGGGGCTTTGTCAACAAGGACCAGATCGCCAAGGATGTGAAGCAGTTC 
                   
               
               
                   
                 TATGACCAGGCCCTACAGCAGGCCGTGGTGGATGATGACGCCAACAACGCCAAGGCTGTGGTG 
                   
               
               
                   
                 AAGACCTTCCACGAGACGCTTGACTGCTGTGGCTCCAGCACACTGACTGCTTTGACCACCTCA 
                   
               
               
                   
                 GTGCTCAAGAACAATTTGTGTCCCTCGGGCAGCAACATCATCAGCAACCTCTTCAAGGAGGAC 
                   
               
               
                   
                 TGCCACCAGAAGATCGATGACCTCTTCTCCGGGAAGCTGTACCTCATCGGCATTGCTGCCATC 
                   
               
               
                   
                 GTGGTCGCTGTGATCATGATCTTCGAGATGATCCTGAGCATGGTGCTGTGCTGTGGCATCCGG 
                   
               
               
                   
                 AACAGCTCCGTGTACTGA 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
             
               
                 TABLE 13 
               
               
                   
               
               
                   
                   
                 SEQ 
               
               
                   
                   
                 ID 
               
               
                   
                 Sequence 
                 NO: 
               
               
                   
               
             
            
               
                 Signal 
                 
                   MARSVTLVFLVLVSLTGLYA 
                 
                   1 
               
               
                 peptide 
                 
                   ATGGCTCGCTCGGTGACCCTGGTCTTTCTGGTGCTTGTCTCACTGACCGGCCTGTATGCT 
                 
                   2 
               
               
                 of β 2   
                   
                   
               
               
                 micro- 
                   
                   
               
               
                 globulin 
                   
                   
               
               
                   
               
               
                 OVA 
                 SIINFEKL 
                   3 
               
               
                 peptide   
                 TCCATTATAAATTTTGAAAAGTTG 
                   4 
               
               
                 1 
                   
                   
               
               
                 (for MHC 
                   
                   
               
               
                 class I 
                   
                   
               
               
                 molecule) 
                   
                   
               
               
                   
               
               
                 Peptide 
                 GGGASGGGGSGGGGS 
                   5 
               
               
                 linker 1 
                 GGCGGAGGTGCCTCTGGCGGTGGGGGCAGCGGTGGAGGGGGCAGT 
                   6 
               
               
                   
               
               
                 β 2   
                 IQKTPQIQVYSRHPPENGKPNILNCYVTQFHPPHIEIQMLKNGKKIPKVEMSDMSFSKDWSFY 
                   7 
               
               
                 Micro- 
                 ILAHTEFTPTETDTYACRVKHASMAEPKTVYWDRDM 
                   
               
               
                 globulin 
                 ATCCAGAAAACCCCTCAAATTCAAGTATACTCACGCCACCCACCGGAGAATGGGAAGCCGAAC 
                   8 
               
               
                 (from  
                 ATACTGAACTGCTACGTAACACAGTTCCACCCGCCTCACATTGAAATCCAAATGCTGAAGAAC 
                   
               
               
                 which 
                 GGGAAAAAAATTCCTAAAGTAGAGATGTCAGATATGTCCTTCAGCAAGGACTGGTCTTTCTAT 
                   
               
               
                 signal  
                 ATCCTGGCTCACACTGAATTCACCCCCACTGAGACTGATACATACGCCTGCAGAGTTAAGCAT 
                   
               
               
                 peptide 
                 GCCAGTATGGCCGAGCCCAAGACCGTCTACTGGGATCGAGACATG 
                   
               
               
                 is 
                   
                   
               
               
                 removed) 
                   
                   
               
               
                   
               
               
                 MHC  
                 GPHSLRYFVTAVSRPGLGEPRYMEVGYVDDTEFVRFDSDAENPRYEPRARWMEQEGPEYWERE 
                   9 
               
               
                 class 
                 TQKAKGNEQSFRVDLRTLLGYYNQSKGGSHTIQVISGCEVGSDGRLLRGYQQYAYDGCDYIAL 
                   
               
               
                 Iα  
                 NEDLKTWTAADMAALITKHKWEQAGEAERLRAYLEGTCVEWLRRYLKNGNATLLRTDSPKAHV 
                   
               
               
                 chain 
                 THHSRPEDKVTLRCWALGFYPADITLTWQLNGEELIQDMELVETRPAGDGTFQKWASVVVPLG 
                   
               
               
                 (from  
                 KEQYYTCHVYHQGLPEPLTLRWEPPPSTVSNMATVAVLVVLGAAIVTGAVVAFVMKMRRRNTG 
                   
               
               
                 which 
                 GKGGDYALAPGSQTSDLSLPDCKVMVHDPHSLA 
                   
               
               
                 signal  
                 GGCCCACACTCGCTGAGGTATTTCGTCACCGCCGTGTCCCGGCCCGGCCTCGGGGAGCCCCGG 
                  10 
               
               
                 peptide 
                 TACATGGAAGTCGGCTACGTGGACGACACGGAGTTCGTGCGCTTCGACAGCGACGCGGAGAAT 
                   
               
               
                 is  
                 CCGAGATATGAGCCGCGGGCGCGGTGGATGGAGCAGGAGGGGCCCGAGTATTGGGAGCGGGAG 
                   
               
               
                 removed) 
                 ACACAGAAAGCCAAGGGCAATGAGCAGAGTTTCCGAGTGGACCTGAGGACCCTGCTCGGCTAC 
                   
               
               
                   
                 TACAACCAGAGCAAGGGCGGCTCTCACACTATTCAGGTGATCTCTGGCTGTGAAGTGGGGTCC 
                   
               
               
                   
                 GACGGGCGACTCCTCCGCGGGTACCAGCAGTACGCCTACGACGGCTGCGATTACATCGCCCTG 
                   
               
               
                   
                 AACGAAGACCTGAAAACGTGGACGGCGGCGGACATGGCGGCGCTGATCACCAAACACAAGTGG 
                   
               
               
                   
                 GAGCAGGCTGGTGAAGCAGAGAGACTCAGGGCCTACCTGGAGGGCACGTGCGTGGAGTGGCTC 
                   
               
               
                   
                 CGCAGATACCTGAAGAACGGGAACGCGACGCTGCTGCGCACAGATTCCCCAAAGGCCCATGTG 
                   
               
               
                   
                 ACCCATCACAGCAGACCTGAAGATAAAGTCACCCTGAGGTGCTGGGCCCTGGGCTTCTACCCT 
                   
               
               
                   
                 GCTGACATCACCCTGACCTGGCAGTTGAATGGGGAGGAGCTGATCCAGGACATGGAGCTTGTG 
                   
               
               
                   
                 GAGACCAGGCCTGCAGGGGATGGAACCTTCCAGAAGTGGGCATCTGTGGTGGTGCCTCTTGGG 
                   
               
               
                   
                 AAGGAGCAGTATTACACATGCCATGTGTACCATCAGGGGCTGCCTGAGCCCCTCACCCTGAGA 
                   
               
               
                   
                 TGGGAGCCTCCTCCATCCACTGTCTCCAACATGGCGACCGTTGCTGTTCTGGTTGTCCTTGGA 
                   
               
               
                   
                 GCTGCAATAGTCACTGGAGCTGTGGTGGCTTTTGTGATGAAGATGAGAAGGAGAAACACAGGT 
                   
               
               
                   
                 GGAAAAGGAGGGGACTATGCTCTGGCTCCAGGCTCCCAGACCTCTGATCTGTCTCTCCCAGAT 
                   
               
               
                   
                 TGTAAAGTGATGGTTCATGACCCTCATTCTCTAGCG 
                   
               
               
                   
               
               
                 Peptide  
                 GGGGSGGGGSGGGGSGGGGS 
                  11 
               
               
                 linker 2 
                 GGGGGGGGAGGCTCCGGTGGAGGGGGGTCTGGAGGGGGGGGGTCTGGTGGAGGCGGAAGT 
                  12 
               
               
                   
               
               
                 Single 
                 IQKTPQIQVYSRHPPENGKPNILNCYVTQFHPPHIEIQMLKNGKKIPKVEMSDMSFSKDWSFY 
                  65 
               
               
                 chain 
                 ILAHTEFTPTETDTYACRVKHASMAEPKTVYWDRDMGGGGSGGGGSGGGGSGGGGSGPHSLRY 
                   
               
               
                 MHC 
                 FVTAVSRPGLGEPRYMEVGYVDDTEFVRFDSDAENPRYEPRARWMEQEGPEYWERETQKAKGN 
                   
               
               
                 class I 
                 EQSFRVDLRTLLGYYNQSKGGSHTIQVISGCEVGSDGRLLRGYQQYAYDGCDYIALNEDLKTW 
                   
               
               
                 molecule 
                 TAADMAALITKHKWEQAGEAERLRAYLEGTCVEWLRRYLKNGNATLLRTDSPKAHVTHHSRPE 
                   
               
               
                 (β 2   
                 DKVTLRCWALGFYPADITLTWQLNGEELIQDMELVETRPAGDGTFQKWASVVVPLGKEQYYTC 
                   
               
               
                 micro- 
                 HVYHQGLPEPLTLRWEPPPSTVSNMATVAVLVVLGAAIVTGAVVAFVMKMRRRNTGGKGGDYA 
                   
               
               
                 globulin 
                 LAPGSQTSDLSLPDCKVMVHDPHSLA 
                   
               
               
                 (from  
                 ATCCAGAAAACCCCTCAAATTCAAGTATACTCACGCCACCCACCGGAGAATGGGAAGCCGAAC 
                  66 
               
               
                 which  
                 ATACTGAACTGCTACGTAACACAGTTCCACCCGCCTCACATTGAAATCCAAATGCTGAAGAAC 
                   
               
               
                 signal 
                 GGGAAAAAAATTCCTAAAGTAGAGATGTCAGATATGTCCTTCAGCAAGGACTGGTCTTTCTAT 
                   
               
               
                 peptide 
                 ATCCTGGCTCACACTGAATTCACCCCCACTGAGACTGATACATACGCCTGCAGAGTTAAGCAT 
                   
               
               
                 is re- 
                 GCCAGTATGGCCGAGCCCAAGACCGTCTACTGGGATCGAGACATGGGGGGGGGAGGCTCCGGT 
                   
               
               
                 moved) +  
                 GGAGGGGGGTCTGGAGGGGGGGGGTCTGGTGGAGGCGGAAGTGGCCCACACTCGCTGAGGTAT 
                   
               
               
                 peptide  
                 TTCGTCACCGCCGTGTCCCGGCCCGGCCTCGGGGAGCCCCGGTACATGGAAGTCGGCTACGTG 
                   
               
               
                 linker 
                 GACGACACGGAGTTCGTGCGCTTCGACAGCGACGCGGAGAATCCGAGATATGAGCCGCGGGCG 
                   
               
               
                 2 + MHC  
                 CGGTGGATGGAGCAGGAGGGGCCCGAGTATTGGGAGCGGGAGACACAGAAAGCCAAGGGCAAT 
                   
               
               
                 class 
                 GAGCAGAGTTTCCGAGTGGACCTGAGGACCCTGCTCGGCTACTACAACCAGAGCAAGGGCGGC 
                   
               
               
                 Iα chain 
                 TCTCACACTATTCAGGTGATCTCTGGCTGTGAAGTGGGGTCCGACGGGCGACTCCTCCGCGGG 
                   
               
               
                 (from  
                 TACCAGCAGTACGCCTACGACGGCTGCGATTACATCGCCCTGAACGAAGACCTGAAAACGTGG 
                   
               
               
                 which 
                 ACGGCGGCGGACATGGCGGCGCTGATCACCAAACACAAGTGGGAGCAGGCTGGTGAAGCAGAG 
                   
               
               
                 signal  
                 AGACTCAGGGCCTACCTGGAGGGCACGTGCGTGGAGTGGCTCCGCAGATACCTGAAGAACGGG 
                   
               
               
                 peptide 
                 AACGCGACGCTGCTGCGCACAGATTCCCCAAAGGCCCATGTGACCCATCACAGCAGACCTGAA 
                   
               
               
                 is 
                 GATAAAGTCACCCTGAGGTGCTGGGCCCTGGGCTTCTACCCTGCTGACATCACCCTGACCTGG 
                   
               
               
                 removed)) 
                 CAGTTGAATGGGGAGGAGCTGATCCAGGACATGGAGCTTGTGGAGACCAGGCCTGCAGGGGAT 
                   
               
               
                   
                 GGAACCTTCCAGAAGTGGGCATCTGTGGTGGTGCCTCTTGGGAAGGAGCAGTATTACACATGC 
                   
               
               
                   
                 CATGTGTACCATCAGGGGCTGCCTGAGCCCCTCACCCTGAGATGGGAGCCTCCTCCATCCACT 
                   
               
               
                   
                 GTCTCCAACATGGCGACCGTTGCTGTTCTGGTTGTCCTTGGAGCTGCAATAGTCACTGGAGCT 
                   
               
               
                   
                 GTGGTGGCTTTTGTGATGAAGATGAGAAGGAGAAACACAGGTGGAAAAGGAGGGGACTATGCT 
                   
               
               
                   
                 CTGGCTCCAGGCTCCCAGACCTCTGATCTGTCTCTCCCAGATTGTAAAGTGATGGTTCATGAC 
                   
               
               
                   
                 CCTCATTCTCTAGCG 
                   
               
               
                   
               
               
                 sc- 
                   MARSVTLVFLVLVSLTGLYA SIINFEKLGGGASGGGGSGGGGSIQKTPQIQVYSRHPPENGKP 
                  13 
               
               
                 Trimer 
                 NILNCYVTQFHPPHIEIQMLKNGKKIPKVEMSDMSFSKDWSFYILAHTEFTPTETDTYACRVK 
                   
               
               
                 (OVA 
                 HASMAEPKTVYWDRDMGGGGSGGGGSGGGGSGGGGSGPHSLRYFVTAVSRPGLGEPRYMEVGY 
                   
               
               
                 peptide 
                 VDDTEFVRFDSDAENPRYEPRARWMEQEGPEYWERETQKAKGNEQSFRVDLRTLLGYYNQSKG 
                   
               
               
                 1 + 
                 GSHTIQVISGCEVGSDGRLLRGYQQYAYDGCDYIALNEDLKTWTAADMAALITKHKWEQAGEA 
                   
               
               
                 peptide 
                 ERLRAYLEGTCVEWLRRYLKNGNATLLRTDSPKAHVTHHSRPEDKVTLRCWALGFYPADITLT 
                   
               
               
                 linker 
                 WQLNGEELIQDMELVETRPAGDGTFQKWASVVVPLGKEQYYTCHVYHQGLPEPLTLRWEPPPS 
                   
               
               
                 1 + 
                 TVSNMATVAVLVVLGAAIVTGAVVAFVMKMRRRNTGGKGGDYALAPGSQTSDLSLPDCKVMVH 
                   
               
               
                 single 
                 DPHSLA 
                   
               
               
                 chain 
                   ATGGCTCGCTCGGTGACCCTGGTCTTTCTGGTGCTTGTCTCACTGACCGGCCTGTATGCT TCC 
                  14 
               
               
                 MHC 
                 ATTATAAATTTTGAAAAGTTGGGCGGAGGTGCCTCTGGCGGTGGGGGCAGCGGTGGAGGGGGC 
                   
               
               
                 class I 
                 AGTATCCAGAAAACCCCTCAAATTCAAGTATACTCACGCCACCCACCGGAGAATGGGAAGCCG 
                   
               
               
                 molecule) 
                 AACATACTGAACTGCTACGTAACACAGTTCCACCCGCCTCACATTGAAATCCAAATGCTGAAG 
                   
               
               
                   
                 AACGGGAAAAAAATTCCTAAAGTAGAGATGTCAGATATGTCCTTCAGCAAGGACTGGTCTTTC 
                   
               
               
                   
                 TATATCCTGGCTCACACTGAATTCACCCCCACTGAGACTGATACATACGCCTGCAGAGTTAAG 
                   
               
               
                   
                 CATGCCAGTATGGCCGAGCCCAAGACCGTCTACTGGGATCGAGACATGGGGGGGGGAGGCTCC 
                   
               
               
                   
                 GGTGGAGGGGGGTCTGGAGGGGGGGGGTCTGGTGGAGGCGGAAGTGGCCCACACTCGCTGAGG 
                   
               
               
                   
                 TATTTCGTCACCGCCGTGTCCCGGCCCGGCCTCGGGGAGCCCCGGTACATGGAAGTCGGCTAC 
                   
               
               
                   
                 GTGGACGACACGGAGTTCGTGCGCTTCGACAGCGACGCGGAGAATCCGAGATATGAGCCGCGG 
                   
               
               
                   
                 GCGCGGTGGATGGAGCAGGAGGGGCCCGAGTATTGGGAGCGGGAGACACAGAAAGCCAAGGGC 
                   
               
               
                   
                 AATGAGCAGAGTTTCCGAGTGGACCTGAGGACCCTGCTCGGCTACTACAACCAGAGCAAGGGC 
                   
               
               
                   
                 GGCTCTCACACTATTCAGGTGATCTCTGGCTGTGAAGTGGGGTCCGACGGGCGACTCCTCCGC 
                   
               
               
                   
                 GGGTACCAGCAGTACGCCTACGACGGCTGCGATTACATCGCCCTGAACGAAGACCTGAAAACG 
                   
               
               
                   
                 TGGACGGCGGCGGACATGGCGGCGCTGATCACCAAACACAAGTGGGAGCAGGCTGGTGAAGCA 
                   
               
               
                   
                 GAGAGACTCAGGGCCTACCTGGAGGGCACGTGCGTGGAGTGGCTCCGCAGATACCTGAAGAAC 
                   
               
               
                   
                 GGGAACGCGACGCTGCTGCGCACAGATTCCCCAAAGGCCCATGTGACCCATCACAGCAGACCT 
                   
               
               
                   
                 GAAGATAAAGTCACCCTGAGGTGCTGGGCCCTGGGCTTCTACCCTGCTGACATCACCCTGACC 
                   
               
               
                   
                 TGGCAGTTGAATGGGGAGGAGCTGATCCAGGACATGGAGCTTGTGGAGACCAGGCCTGCAGGG 
                   
               
               
                   
                 GATGGAACCTTCCAGAAGTGGGCATCTGTGGTGGTGCCTCTTGGGAAGGAGCAGTATTACACA 
                   
               
               
                   
                 TGCCATGTGTACCATCAGGGGCTGCCTGAGCCCCTCACCCTGAGATGGGAGCCTCCTCCATCC 
                   
               
               
                   
                 ACTGTCTCCAACATGGCGACCGTTGCTGTTCTGGTTGTCCTTGGAGCTGCAATAGTCACTGGA 
                   
               
               
                   
                 GCTGTGGTGGCTTTTGTGATGAAGATGAGAAGGAGAAACACAGGTGGAAAAGGAGGGGACTAT 
                   
               
               
                   
                 GCTCTGGCTCCAGGCTCCCAGACCTCTGATCTGTCTCTCCCAGATTGTAAAGTGATGGTTCAT 
                   
               
               
                   
                 GACCCTCATTCTCTAGCG 
                   
               
               
                   
               
               
                 IL-2 
                 APTSSSTSSSTAEAQQQQQQQQQQQQHLEQLLMDLQELLSRMENYRNLKLPRMLTFKFYLPKQ 
                  25 
               
               
                 (from 
                 ATELKDLQCLEDELGPLRHVLDLTQSKSFQLEDAENFISNIRVTVVKLKGSDNTFECQFDDES 
                   
               
               
                 which 
                 ATVVDFLRRWIAFCQSIISTSPQ 
                   
               
               
                 signal  
                 GCACCCACTTCAAGCTCCACTTCAAGCTCTACAGCGGAAGCACAGCAGCAGCAGCAGCAGCAG 
                  26 
               
               
                 peptide 
                 CAGCAGCAGCAGCAGCACCTGGAGCAGCTGTTGATGGACCTACAGGAGCTCCTGAGCAGGATG 
                   
               
               
                 is  
                 GAGAATTACAGGAACCTGAAACTCCCCAGGATGCTCACCTTCAAATTTTACTTGCCCAAGCAG 
                   
               
               
                 removed) 
                 GCCACAGAATTGAAAGATCTTCAGTGCCTAGAAGATGAACTTGGACCTCTGCGGCATGTTCTG 
                   
               
               
                   
                 GATTTGACTCAAAGCAAAAGCTTTCAATTGGAAGATGCTGAGAATTTCATCAGCAATATCAGA 
                   
               
               
                   
                 GTAACTGTTGTAAAACTAAAGGGCTCTGACAACACATTTGAGTGCCAATTCGATGATGAGTCA 
                   
               
               
                   
                 GCAACTGTGGTGGACTTTCTGAGGAGATGGATAGCCTTCTGTCAAAGCATCATCTCAACAAGC 
                   
               
               
                   
                 CCTCAA 
                   
               
               
                   
               
               
                 CD81 
                 MGVEGCTKCIKYLLFVFNFVFWLAGGVILGVALWLRHDPQTTSLLYLELGNKPAPNTFYVGIY 
                  61 
               
               
                 (amino  
                 ILIAVGAVMMFVGFLGCYGAIQESQCLLGTFFTCLVILFACEVAAGIWGFVNKDQIAKDVKQF 
                   
               
               
                 acids 
                 YDQALQQAVMDDDANNAKAVVKTFHETLNCCGSNALTTLTTTILRNSLCPS 
                   
               
               
                 1 to  
                 ATGGGGGTGGAGGGCTGCACCAAATGCATCAAATACCTGCTCTTCGTCTTCAATTTCGTCTTC 
                  62 
               
               
                 177) 
                 TGGCTGGCTGGAGGCGTGATCCTAGGTGTAGCTCTGTGGTTGCGTCATGATCCACAGACCACC 
                   
               
               
                   
                 AGCCTGCTGTACCTGGAACTGGGAAACAAACCGGCACCCAACACCTTCTACGTGGGCATCTAC 
                   
               
               
                   
                 ATTCTCATTGCTGTGGGAGCTGTGATGATGTTTGTAGGCTTCCTGGGGTGCTATGGGGCCATC 
                   
               
               
                   
                 CAGGAGTCCCAGTGTCTGCTGGGGACGTTCTTCACCTGCCTTGTGATCCTGTTTGCCTGTGAG 
                   
               
               
                   
                 GTGGCTGCAGGCATCTGGGGCTTCGTAAACAAAGACCAGATCGCCAAGGATGTGAAGCAGTTC 
                   
               
               
                   
                 TATGACCAGGCCCTTCAGCAAGCTGTGATGGATGATGATGCCAACAATGCCAAGGCTGTGGTG 
                   
               
               
                   
                 AAGACTTTCCATGAGACGCTCAACTGTTGTGGCTCCAACGCACTGACCACACTGACTACCACC 
                   
               
               
                   
                 ATACTGAGGAACAGCCTGTGTCCCTCA 
                   
               
               
                   
               
               
                 CD81 
                 GGNILTPLLQQDCHQKIDELFSGKLYLIGIAAIVVAVIMIFEMILSMVLCCGIRNSSVY 
                  63 
               
               
                 (amino  
                 GGCGGCAACATACTCACCCCCTTACTGCAGCAAGATTGTCATCAGAAAATCGATGAGCTCTTC 
                  64 
               
               
                 acids 
                 TCTGGGAAGCTGTACCTCATTGGAATTGCAGCCATTGTGGTAGCTGTCATTATGATCTTTGAG 
                   
               
               
                 178 to  
                 ATGATTCTGAGCATGGTGCTGTGCTGTGGCATCCGGAACAGCTCCGTGTACTGA 
                   
               
               
                 236) 
                   
                   
               
               
                   
               
               
                 CD81-  
                 MGVEGCTKCIKYLLFVFNFVFWLAGGVILGVALWLRHDPQTTSLLYLELGNKPAPNTFYVGIY 
                 133 
               
               
                 IL-2 
                 ILIAVGAVMMFVGFLGCYGAIQESQCLLGTFFTCLVILFACEVAAGIWGFVNKDQIAKDVKQF 
                   
               
               
                   
                 YDQALQQAVMDDDANNAKAVVKTFHETLNCCGSNALTTLTTTILRNSLCPSGGGGSAPTSSST 
                   
               
               
                   
                 SSSTAEAQQQQQQQQQQQQHLEQLLMDLQELLSRMENYRNLKLPRMLTFKFYLPKQATELKDL 
                   
               
               
                   
                 QCLEDELGPLRHVLDLTQSKSFQLEDAENFISNIRVTVVKLKGSDNTFECQFDDESATVVDFL 
                   
               
               
                   
                 RRWIAFCQSIISTSPQGGGGSGGNILTPLLQQDCHQKIDELFSGKLYLIGIAAIVVAVIMIFE 
                   
               
               
                   
                 MILSMVLCCGIRNSSVY 
                   
               
               
                   
                 ATGGGGGTGGAGGGCTGCACCAAATGCATCAAATACCTGCTCTTCGTCTTCAATTTCGTCTTC 
                 134 
               
               
                   
                 TGGCTGGCTGGAGGCGTGATCCTAGGTGTAGCTCTGTGGTTGCGTCATGATCCACAGACCACC 
                   
               
               
                   
                 AGCCTGCTGTACCTGGAACTGGGAAACAAACCGGCACCCAACACCTTCTACGTGGGCATCTAC 
                   
               
               
                   
                 ATTCTCATTGCTGTGGGAGCTGTGATGATGTTTGTAGGCTTCCTGGGGTGCTATGGGGCCATC 
                   
               
               
                   
                 CAGGAGTCCCAGTGTCTGCTGGGGACGTTCTTCACCTGCCTTGTGATCCTGTTTGCCTGTGAG 
                   
               
               
                   
                 GTGGCTGCAGGCATCTGGGGCTTCGTAAACAAAGACCAGATCGCCAAGGATGTGAAGCAGTTC 
                   
               
               
                   
                 TATGACCAGGCCCTTCAGCAAGCTGTGATGGATGATGATGCCAACAATGCCAAGGCTGTGGTG 
                   
               
               
                   
                 AAGACTTTCCATGAGACGCTCAACTGTTGTGGCTCCAACGCACTGACCACACTGACTACCACC 
                   
               
               
                   
                 ATACTGAGGAACAGCCTGTGTCCCTCAGGAGGAGGAGGAAGCGCACCCACTTCAAGCTCCACT 
                   
               
               
                   
                 TCAAGCTCTACAGCGGAAGCACAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCAGCACCTG 
                   
               
               
                   
                 GAGCAGCTGTTGATGGACCTACAGGAGCTCCTGAGCAGGATGGAGAATTACAGGAACCTGAAA 
                   
               
               
                   
                 CTCCCCAGGATGCTCACCTTCAAATTTTACTTGCCCAAGCAGGCCACAGAATTGAAAGATCTT 
                   
               
               
                   
                 CAGTGCCTAGAAGATGAACTTGGACCTCTGCGGCATGTTCTGGATTTGACTCAAAGCAAAAGC 
                   
               
               
                   
                 TTTCAATTGGAAGATGCTGAGAATTTCATCAGCAATATCAGAGTAACTGTTGTAAAACTAAAG 
                   
               
               
                   
                 GGCTCTGACAACACATTTGAGTGCCAATTCGATGATGAGTCAGCAACTGTGGTGGACTTTCTG 
                   
               
               
                   
                 AGGAGATGGATAGCCTTCTGTCAAAGCATCATCTCAACAAGCCCTCAAGGAGGAGGAGGAAGC 
                   
               
               
                   
                 GGCGGCAACATACTCACCCCCTTACTGCAGCAAGATTGTCATCAGAAAATCGATGAGCTCTTC 
                   
               
               
                   
                 TCTGGGAAGCTGTACCTCATTGGAATTGCAGCCATTGTGGTAGCTGTCATTATGATCTTTGAG 
                   
               
               
                   
                 ATGATTCTGAGCATGGTGCTGTGCTGTGGCATCCGGAACAGCTCCGTGTACTGA 
                   
               
               
                   
               
               
                 sc- 
                   MARSVTLVFLVLVSLTGLYA SIINFEKLGGGASGGGGSGGGGSIQKTPQIQVYSRHPPENGKP 
                 135 
               
               
                 Trimer- 
                 NILNCYVTQFHPPHIEIQMLKNGKKIPKVEMSDMSFSKDWSFYILAHTEFTPTETDTYACRVK 
                   
               
               
                 CD81- 
                 HASMAEPKTVYWDRDMGGGGSGGGGSGGGGSGGGGSGPHSLRYFVTAVSRPGLGEPRYMEVGY 
                   
               
               
                 IL-2 
                 VDDTEFVRFDSDAENPRYEPRARWMEQEGPEYWERETQKAKGNEQSFRVDLRTLLGYYNQSKG 
                   
               
               
                 (sc- 
                 GSHTIQVISGCEVGSDGRLLRGYQQYAYDGCDYIALNEDLKTWTAADMAALITKHKWEQAGEA 
                   
               
               
                 Trimer + 
                 ERLRAYLEGTCVEWLRRYLKNGNATLLRTDSPKAHVTHHSRPEDKVTLRCWALGFYPADITLT 
                   
               
               
                 CD81) 
                 WQLNGEELIQDMELVETRPAGDGTFQKWASVVVPLGKEQYYTCHVYHQGLPEPLTLRWEPPPS 
                   
               
               
                   
                 TVSNMATVAVLVVLGAAIVTGAVVAFVMKMRRRNTGGKGGDYALAPGSQTSDLSLPDCKVMVH 
                   
               
               
                   
                 DPHSLAMGVEGCTKCIKYLLFVFNFVFWLAGGVILGVALWLRHDPQTTSLLYLELGNKPAPNT 
                   
               
               
                   
                 FYVGIYILIAVGAVMMFVGFLGCYGAIQESQCLLGTFFTCLVILFACEVAAGIWGFVNKDQIA 
                   
               
               
                   
                 KDVKQFYDQALQQAVMDDDANNAKAVVKTFHETLNCCGSNALTTLTTTILRNSLCPSGGGGSA 
                   
               
               
                   
                 PTSSSTSSSTAEAQQQQQQQQQQQQHLEQLLMDLQELLSRMENYRNLKLPRMLTFKFYLPKQA 
                   
               
               
                   
                 TELKDLQCLEDELGPLRHVLDLTQSKSFQLEDAENFISNIRVTVVKLKGSDNTFECQFDDESA 
                   
               
               
                   
                 TVVDFLRRWIAFCQSIISTSPQGGGGSGGNILTPLLQQDCHQKIDELFSGKLYLIGIAAIVVA 
                   
               
               
                   
                 VIMIFEMILSMVLCCGIRNSSVY 
                   
               
               
                   
                 ATGGCTCGCTCGGTGACCCTGGTCTTTCTGGTGCTTGTCTCACTGACCGGCCTGTATGCTTCC 
                 136 
               
               
                   
                 ATTATAAATTTTGAAAAGTTGGGCGGAGGTGCCTCTGGCGGTGGGGGCAGCGGTGGAGGGGGC 
                   
               
               
                   
                 AGTATCCAGAAAACCCCTCAAATTCAAGTATACTCACGCCACCCACCGGAGAATGGGAAGCCG 
                   
               
               
                   
                 AACATACTGAACTGCTACGTAACACAGTTCCACCCGCCTCACATTGAAATCCAAATGCTGAAG 
                   
               
               
                   
                 AACGGGAAAAAAATTCCTAAAGTAGAGATGTCAGATATGTCCTTCAGCAAGGACTGGTCTTTC 
                   
               
               
                   
                 TATATCCTGGCTCACACTGAATTCACCCCCACTGAGACTGATACATACGCCTGCAGAGTTAAG 
                   
               
               
                   
                 CATGCCAGTATGGCCGAGCCCAAGACCGTCTACTGGGATCGAGACATGGGGGGGGGAGGCTCC 
                   
               
               
                   
                 GGTGGAGGGGGGTCTGGAGGGGGGGGGTCTGGTGGAGGCGGAAGTGGCCCACACTCGCTGAGG 
                   
               
               
                   
                 TATTTCGTCACCGCCGTGTCCCGGCCCGGCCTCGGGGAGCCCCGGTACATGGAAGTCGGCTAC 
                   
               
               
                   
                 GTGGACGACACGGAGTTCGTGCGCTTCGACAGCGACGCGGAGAATCCGAGATATGAGCCGCGG 
                   
               
               
                   
                 GCGCGGTGGATGGAGCAGGAGGGGCCCGAGTATTGGGAGCGGGAGACACAGAAAGCCAAGGGC 
                   
               
               
                   
                 AATGAGCAGAGTTTCCGAGTGGACCTGAGGACCCTGCTCGGCTACTACAACCAGAGCAAGGGC 
                   
               
               
                   
                 GGCTCTCACACTATTCAGGTGATCTCTGGCTGTGAAGTGGGGTCCGACGGGCGACTCCTCCGC 
                   
               
               
                   
                 GGGTACCAGCAGTACGCCTACGACGGCTGCGATTACATCGCCCTGAACGAAGACCTGAAAACG 
                   
               
               
                   
                 TGGACGGCGGCGGACATGGCGGCGCTGATCACCAAACACAAGTGGGAGCAGGCTGGTGAAGCA 
                   
               
               
                   
                 GAGAGACTCAGGGCCTACCTGGAGGGCACGTGCGTGGAGTGGCTCCGCAGATACCTGAAGAAC 
                   
               
               
                   
                 GGGAACGCGACGCTGCTGCGCACAGATTCCCCAAAGGCCCATGTGACCCATCACAGCAGACCT 
                   
               
               
                   
                 GAAGATAAAGTCACCCTGAGGTGCTGGGCCCTGGGCTTCTACCCTGCTGACATCACCCTGACC 
                   
               
               
                   
                 TGGCAGTTGAATGGGGAGGAGCTGATCCAGGACATGGAGCTTGTGGAGACCAGGCCTGCAGGG 
                   
               
               
                   
                 GATGGAACCTTCCAGAAGTGGGCATCTGTGGTGGTGCCTCTTGGGAAGGAGCAGTATTACACA 
                   
               
               
                   
                 TGCCATGTGTACCATCAGGGGCTGCCTGAGCCCCTCACCCTGAGATGGGAGCCTCCTCCATCC 
                   
               
               
                   
                 ACTGTCTCCAACATGGCGACCGTTGCTGTTCTGGTTGTCCTTGGAGCTGCAATAGTCACTGGA 
                   
               
               
                   
                 GCTGTGGTGGCTTTTGTGATGAAGATGAGAAGGAGAAACACAGGTGGAAAAGGAGGGGACTAT 
                   
               
               
                   
                 GCTCTGGCTCCAGGCTCCCAGACCTCTGATCTGTCTCTCCCAGATTGTAAAGTGATGGTTCAT 
                   
               
               
                   
                 GACCCTCATTCTCTAGCGATGGGGGTGGAGGGCTGCACCAAATGCATCAAATACCTGCTCTTC 
                   
               
               
                   
                 GTCTTCAATTTCGTCTTCTGGCTGGCTGGAGGCGTGATCCTAGGTGTAGCTCTGTGGTTGCGT 
                   
               
               
                   
                 CATGATCCACAGACCACCAGCCTGCTGTACCTGGAACTGGGAAACAAACCGGCACCCAACACC 
                   
               
               
                   
                 TTCTACGTGGGCATCTACATTCTCATTGCTGTGGGAGCTGTGATGATGTTTGTAGGCTTCCTG 
                   
               
               
                   
                 GGGTGCTATGGGGCCATCCAGGAGTCCCAGTGTCTGCTGGGGACGTTCTTCACCTGCCTTGTG 
                   
               
               
                   
                 ATCCTGTTTGCCTGTGAGGTGGCTGCAGGCATCTGGGGCTTCGTAAACAAAGACCAGATCGCC 
                   
               
               
                   
                 AAGGATGTGAAGCAGTTCTATGACCAGGCCCTTCAGCAAGCTGTGATGGATGATGATGCCAAC 
                   
               
               
                   
                 AATGCCAAGGCTGTGGTGAAGACTTTCCATGAGACGCTCAACTGTTGTGGCTCCAACGCACTG 
                   
               
               
                   
                 ACCACACTGACTACCACCATACTGAGGAACAGCCTGTGTCCCTCAGGAGGAGGAGGAAGCGCA 
                   
               
               
                   
                 CCCACTTCAAGCTCCACTTCAAGCTCTACAGCGGAAGCACAGCAGCAGCAGCAGCAGCAGCAG 
                   
               
               
                   
                 CAGCAGCAGCAGCACCTGGAGCAGCTGTTGATGGACCTACAGGAGCTCCTGAGCAGGATGGAG 
                   
               
               
                   
                 AATTACAGGAACCTGAAACTCCCCAGGATGCTCACCTTCAAATTTTACTTGCCCAAGCAGGCC 
                   
               
               
                   
                 ACAGAATTGAAAGATCTTCAGTGCCTAGAAGATGAACTTGGACCTCTGCGGCATGTTCTGGAT 
                   
               
               
                   
                 TTGACTCAAAGCAAAAGCTTTCAATTGGAAGATGCTGAGAATTTCATCAGCAATATCAGAGTA 
                   
               
               
                   
                 ACTGTTGTAAAACTAAAGGGCTCTGACAACACATTTGAGTGCCAATTCGATGATGAGTCAGCA 
                   
               
               
                   
                 ACTGTGGTGGACTTTCTGAGGAGATGGATAGCCTTCTGTCAAAGCATCATCTCAACAAGCCCT 
                   
               
               
                   
                 CAAGGAGGAGGAGGAAGCGGCGGCAACATACTCACCCCCTTACTGCAGCAAGATTGTCATCAG 
                   
               
               
                   
                 AAAATCGATGAGCTCTTCTCTGGGAAGCTGTACCTCATTGGAATTGCAGCCATTGTGGTAGCT 
                   
               
               
                   
                 GTCATTATGATCTTTGAGATGATTCTGAGCATGGTGCTGTGCTGTGGCATCCGGAACAGCTCC 
                   
               
               
                   
                 GTGTACTGA 
                   
               
               
                   
               
               
                 Aka-Luc 
                 MEDAKNIKKGPAPFYPLEDGTAGEQLHKAMKRYALVPGAIAFTDAHIQVDVTYAEYFEMSVRL 
                 137 
               
               
                   
                 AEAMRRYGLNTNHRIVVCSENSSQFFMPVLGALFIGVAVAPANDIYNERELLNSMGISQPTVV 
                   
               
               
                   
                 FVSKKGLRKVLNVQKKLPIIRKIIIMDSKTDYQGFQSMYTFVTSHLPPSFNEYDFVPESFDRD 
                   
               
               
                   
                 KTIALIMNSSGSTGLPKGVALPHRTACVRFSHARDPIFGYQNIPDTAILSVVPFHHGFGMFTT 
                   
               
               
                   
                 LGYLICGFRVVLMYRFEEELFLRSLQDYKIQSALLVPTLFSCLAKSTLIDKYDLSSLREIASG 
                   
               
               
                   
                 GAPLSKEVGEAVAKRFRLPGIRQGYGLTETTNAVMITPEGDRKPGSVGKVVPFFEAKVVDLVT 
                   
               
               
                   
                 GKTLGVNQRGELCVRGPMIMSGYVNNPEATNALIDKDGWLHSGDIAYWDEDEHFFIVDRLKSL 
                   
               
               
                   
                 IKYKGYQVAPAELEGILLQHPYIFDAGVAGLPDDDAGELPAAVVVLEHGKTMTEKEIVDYVAS 
                   
               
               
                   
                 QVTTAKKLRGGVVFVDEVPRGSTGKLDARKIREILTKAKKDGKIAV 
                   
               
               
                   
                 ATGGAAGATGCCAAAAACATTAAGAAGGGCCCAGCGCCGTTCTACCCACTCGAAGACGGGACC 
                 138 
               
               
                   
                 GCCGGCGAGCAGCTGCACAAAGCCATGAAGCGCTACGCCCTGGTGCCCGGCGCCATCGCCTTT 
                   
               
               
                   
                 ACCGACGCACATATTCAGGTGGACGTTACCTACGCCGAGTACTTCGAGATGAGCGTTCGGCTG 
                   
               
               
                   
                 GCAGAAGCTATGAGGCGCTATGGGCTGAATACAAACCATCGGATCGTGGTGTGCAGCGAGAAT 
                   
               
               
                   
                 AGCTCGCAGTTCTTCATGCCCGTGTTGGGTGCCCTGTTCATCGGTGTGGCTGTGGCCCCAGCT 
                   
               
               
                   
                 AACGACATCTACAACGAGCGCGAGCTGCTGAACAGCATGGGCATCAGCCAGCCCACCGTCGTA 
                   
               
               
                   
                 TTCGTGAGCAAGAAAGGGCTGCGAAAGGTCCTCAACGTGCAAAAGAAGCTACCGATCATACGA 
                   
               
               
                   
                 AAGATCATCATCATGGATAGCAAGACCGACTACCAGGGCTTCCAAAGCATGTACACCTTCGTG 
                   
               
               
                   
                 ACTTCCCATTTGCCACCCAGCTTCAACGAGTACGACTTCGTGCCCGAGAGCTTCGACCGGGAC 
                   
               
               
                   
                 AAAACCATCGCCCTGATCATGAACAGTAGTGGTAGTACAGGATTACCCAAGGGCGTAGCCCTA 
                   
               
               
                   
                 CCGCACCGCACCGCTTGTGTCCGATTCAGTCATGCCCGCGACCCCATCTTCGGCTACCAGAAC 
                   
               
               
                   
                 ATCCCCGACACCGCTATCCTCAGCGTGGTGCCATTTCACCACGGCTTCGGCATGTTCACCACG 
                   
               
               
                   
                 CTGGGCTACTTGATCTGCGGCTTTCGGGTCGTGCTCATGTACCGCTTCGAGGAGGAGCTATTC 
                   
               
               
                   
                 TTGCGCAGCTTGCAAGACTATAAGATTCAATCTGCCCTGCTGGTGCCCACACTATTTAGCTGC 
                   
               
               
                   
                 CTCGCTAAGAGCACTCTCATCGACAAGTACGACCTAAGCAGCTTGCGCGAGATCGCCAGCGGC 
                   
               
               
                   
                 GGGGCGCCGCTCAGCAAGGAGGTAGGTGAGGCCGTGGCCAAACGCTTCCGCCTACCAGGCATC 
                   
               
               
                   
                 CGCCAGGGCTATGGCCTGACAGAAACAACCAACGCCGTCATGATCACCCCCGAGGGGGACCGT 
                   
               
               
                   
                 AAGCCTGGCTCAGTAGGCAAGGTGGTGCCCTTCTTCGAGGCTAAGGTGGTAGACTTGGTCACC 
                   
               
               
                   
                 GGTAAGACACTGGGTGTGAACCAGCGCGGTGAGCTGTGCGTCCGTGGCCCCATGATCATGAGC 
                   
               
               
                   
                 GGCTACGTTAACAACCCCGAGGCTACGAACGCTCTCATCGACAAGGACGGCTGGCTGCACAGC 
                   
               
               
                   
                 GGCGACATCGCCTACTGGGACGAGGACGAGCACTTCTTCATCGTGGACCGGCTGAAGAGCCTG 
                   
               
               
                   
                 ATCAAATACAAGGGCTACCAGGTAGCCCCAGCCGAACTGGAGGGCATCCTGCTGCAACACCCC 
                   
               
               
                   
                 TACATCTTCGACGCCGGAGTCGCCGGCCTGCCCGACGACGATGCCGGCGAGCTGCCCGCCGCA 
                   
               
               
                   
                 GTCGTCGTGTTGGAACACGGTAAAACCATGACCGAGAAAGAGATCGTGGACTATGTGGCCAGC 
                   
               
               
                   
                 CAGGTTACAACCGCCAAGAAGCTGCGCGGTGGTGTTGTGTTTGTGGATGAAGTCCCTAGAGGA 
                   
               
               
                   
                 TCGACCGGCAAGTTAGACGCCCGCAAGATCCGCGAGATTCTCACTAAGGCCAAGAAGGACGGC 
                   
               
               
                   
                 AAGATCGCCGTG 
                   
               
               
                   
               
               
                 CD63 
                 MAVEGGMKCVKFLLYVLLLAFCACAVGLIAIGVAVQVVLKQAITHETTAGSLLPVVIIAVGAF 
                  27 
               
               
                   
                 LFLVAFVGCCGACKENYCLMITFAIFLSLIMLVEVAVAIAGYVFRDQVKSEFNKSFQQQMQNY 
                   
               
               
                   
                 LKDNKTATILDKLQKENNCCGASNYTDWENIPGMAKDRVPDSCCINITVGCGNDFKESTIHTQ 
                   
               
               
                   
                 GCVETIAIWLRKNILLVAAAALGIAFVEVLGIIFSCCLVKSIRSGYEVM 
                   
               
               
                   
                 ATGGCGGTGGAAGGAGGAATGAAGTGTGTCAAGTTTTTGCTCTACGTTCTCCTGCTGGCCTTC 
                  28 
               
               
                   
                 TGCGCCTGTGCAGTGGGATTGATCGCCATTGGTGTAGCGGTTCAGGTTGTCTTGAAGCAGGCC 
                   
               
               
                   
                 ATTACCCATGAGACTACTGCTGGCTCGCTGTTGCCTGTGGTCATCATTGCAGTGGGTGCCTTC 
                   
               
               
                   
                 CTCTTCCTGGTGGCCTTTGTGGGCTGCTGTGGGGCCTGCAAGGAGAACTACTGTCTCATGATT 
                   
               
               
                   
                 ACATTTGCCATCTTCCTGTCTCTTATCATGCTTGTGGAGGTGGCTGTGGCCATTGCTGGCTAT 
                   
               
               
                   
                 GTGTTTAGAGACCAGGTGAAGTCAGAGTTTAATAAAAGCTTCCAGCAGCAGATGCAGAATTAC 
                   
               
               
                   
                 CTTAAAGACAACAAAACAGCCACTATTTTGGACAAATTGCAGAAAGAAAATAACTGCTGTGGA 
                   
               
               
                   
                 GCTTCTAACTACACAGACTGGGAAAACATCCCCGGCATGGCCAAGGACAGAGTCCCCGATTCT 
                   
               
               
                   
                 TGCTGCATCAACATAACTGTGGGCTGTGGGAATGATTTCAAGGAATCCACTATCCATACCCAG 
                   
               
               
                   
                 GGCTGCGTGGAGACTATAGCAATATGGCTAAGGAAGAACATACTGCTGGTGGCTGCAGCGGCC 
                   
               
               
                   
                 CTGGGCATTGCTTTTGTGGAGGTCTTGGGAATTATCTTCTCCTGCTGTCTGGTGAAGAGTATT 
                   
               
               
                   
                 CGAAGTGGCTATGAAGTAATGTAG 
                   
               
               
                   
               
               
                 CD63 
                 MAVEGGMKCVKFLLYVLLLAFCACAVGLIAIGVAVQVVLKQAITHETTAGSLLPVVIIAVGAF 
                  57 
               
               
                 (amino 
                 LFLVAFVGCCGACKENYCLMITFAIFLSLIMLVEVAVAIAGYVFRDQVKSEFNKSFQQQMQNY 
                   
               
               
                 acids 
                 LKDNKTATILDKLQKENNCCGASNYTDWENIPGMAKDRVPDSCC 
                   
               
               
                 1 to 
                 ATGGCGGTGGAAGGAGGAATGAAGTGTGTCAAGTTTTTGCTCTACGTTCTCCTGCTGGCCTTC 
                  58 
               
               
                 170) 
                 TGCGCCTGTGCAGTGGGATTGATCGCCATTGGTGTAGCGGTTCAGGTTGTCTTGAAGCAGGCC 
                   
               
               
                   
                 ATTACCCATGAGACTACTGCTGGCTCGCTGTTGCCTGTGGTCATCATTGCAGTGGGTGCCTTC 
                   
               
               
                   
                 CTCTTCCTGGTGGCCTTTGTGGGCTGCTGTGGGGCCTGCAAGGAGAACTACTGTCTCATGATT 
                   
               
               
                   
                 ACATTTGCCATCTTCCTGTCTCTTATCATGCTTGTGGAGGTGGCTGTGGCCATTGCTGGCTAT 
                   
               
               
                   
                 GTGTTTAGAGACCAGGTGAAGTCAGAGTTTAATAAAAGCTTCCAGCAGCAGATGCAGAATTAC 
                   
               
               
                   
                 CTTAAAGACAACAAAACAGCCACTATTTTGGACAAATTGCAGAAAGAAAATAACTGCTGTGGA 
                   
               
               
                   
                 GCTTCTAACTACACAGACTGGGAAAACATCCCCGGCATGGCCAAGGACAGAGTCCCCGATTCT 
                   
               
               
                   
                 TGCTGC 
                   
               
               
                   
               
               
                 CD63 
                 INITVGCGNDFKESTIHTQGCVETIAIWLRKNILLVAAAALGIAFVEVLGIIFSCCLVKSIRS 
                  59 
               
               
                 (amino 
                 GYEVM 
                   
               
               
                 acids 
                 ATCAACATAACTGTGGGCTGTGGGAATGATTTCAAGGAATCCACTATCCATACCCAGGGCTGC 
                  60 
               
               
                 171 to  
                 GTGGAGACTATAGCAATATGGCTAAGGAAGAACATACTGCTGGTGGCTGCAGCGGCCCTGGGC 
                   
               
               
                 238) 
                 ATTGCTTTTGTGGAGGTCTTGGGAATTATCTTCTCCTGCTGTCTGGTGAAGAGTATTCGAAGT 
                   
               
               
                   
                 GGCTATGAAGTAATGTAG 
                   
               
               
                   
               
               
                 Peptide  
                 GGGGS 
                  29 
               
               
                 linker 3 
                 GGAGGAGGAGGAAGC 
                  30 
               
               
                   
               
               
                 CD63- 
                 MAVEGGMKCVKFLLYVLLLAFCACAVGLIAIGVAVQVVLKQAITHETTAGSLLPVVIIAVGAF 
                 139 
               
               
                 Aka-Luc 
                 LFLVAFVGCCGACKENYCLMITFAIFLSLIMLVEVAVAIAGYVFRDQVKSEFNKSFQQQMQNY 
                   
               
               
                   
                 LKDNKTATILDKLQKENNCCGASNYTDWENIPGMAKDRVPDSCCGGGGSMEDAKNIKKGPAPF 
                   
               
               
                   
                 YPLEDGTAGEQLHKAMKRYALVPGAIAFTDAHIQVDVTYAEYFEMSVRLAEAMRRYGLNTNHR 
                   
               
               
                   
                 IVVCSENSSQFFMPVLGALFIGVAVAPANDIYNERELLNSMGISQPTVVFVSKKGLRKVLNVQ 
                   
               
               
                   
                 KKLPIIRKIIIMDSKTDYQGFQSMYTFVTSHLPPSFNEYDFVPESFDRDKTIALIMNSSGSTG 
                   
               
               
                   
                 LPKGVALPHRTACVRFSHARDPIFGYQNIPDTAILSVVPFHHGFGMFTTLGYLICGFRVVLMY 
                   
               
               
                   
                 RFEEELFLRSLQDYKIQSALLVPTLFSCLAKSTLIDKYDLSSLREIASGGAPLSKEVGEAVAK 
                   
               
               
                   
                 RFRLPGIRQGYGLTETTNAVMITPEGDRKPGSVGKVVPFFEAKVVDLVTGKTLGVNQRGELCV 
                   
               
               
                   
                 RGPMIMSGYVNNPEATNALIDKDGWLHSGDIAYWDEDEHFFIVDRLKSLIKYKGYQVAPAELE 
                   
               
               
                   
                 GILLQHPYIFDAGVAGLPDDDAGELPAAVVVLEHGKTMTEKEIVDYVASQVTTAKKLRGGVVF 
                   
               
               
                   
                 VDEVPRGSTGKLDARKIREILTKAKKDGKIAVGGGGSINITVGCGNDFKESTIHTQGCVETIA 
                   
               
               
                   
                 IWLRKNILLVAAAALGIAFVEVLGIIFSCCLVKSIRSGYEVM 
                   
               
               
                   
                 ATGGCGGTGGAAGGAGGAATGAAGTGTGTCAAGTTTTTGCTCTACGTTCTCCTGCTGGCCTTC 
                 140 
               
               
                   
                 TGCGCCTGTGCAGTGGGATTGATCGCCATTGGTGTAGCGGTTCAGGTTGTCTTGAAGCAGGCC 
                   
               
               
                   
                 ATTACCCATGAGACTACTGCTGGCTCGCTGTTGCCTGTGGTCATCATTGCAGTGGGTGCCTTC 
                   
               
               
                   
                 CTCTTCCTGGTGGCCTTTGTGGGCTGCTGTGGGGCCTGCAAGGAGAACTACTGTCTCATGATT 
                   
               
               
                   
                 ACATTTGCCATCTTCCTGTCTCTTATCATGCTTGTGGAGGTGGCTGTGGCCATTGCTGGCTAT 
                   
               
               
                   
                 GTGTTTAGAGACCAGGTGAAGTCAGAGTTTAATAAAAGCTTCCAGCAGCAGATGCAGAATTAC 
                   
               
               
                   
                 CTTAAAGACAACAAAACAGCCACTATTTTGGACAAATTGCAGAAAGAAAATAACTGCTGTGGA 
                   
               
               
                   
                 GCTTCTAACTACACAGACTGGGAAAACATCCCCGGCATGGCCAAGGACAGAGTCCCCGATTCT 
                   
               
               
                   
                 TGCTGCGGTGGTGGTGGTTCTATGGAAGATGCCAAAAACATTAAGAAGGGCCCAGCGCCGTTC 
                   
               
               
                   
                 TACCCACTCGAAGACGGGACCGCCGGCGAGCAGCTGCACAAAGCCATGAAGCGCTACGCCCTG 
                   
               
               
                   
                 GTGCCCGGCGCCATCGCCTTTACCGACGCACATATTCAGGTGGACGTTACCTACGCCGAGTAC 
                   
               
               
                   
                 TTCGAGATGAGCGTTCGGCTGGCAGAAGCTATGAGGCGCTATGGGCTGAATACAAACCATCGG 
                   
               
               
                   
                 ATCGTGGTGTGCAGCGAGAATAGCTCGCAGTTCTTCATGCCCGTGTTGGGTGCCCTGTTCATC 
                   
               
               
                   
                 GGTGTGGCTGTGGCCCCAGCTAACGACATCTACAACGAGCGCGAGCTGCTGAACAGCATGGGC 
                   
               
               
                   
                 ATCAGCCAGCCCACCGTCGTATTCGTGAGCAAGAAAGGGCTGCGAAAGGTCCTCAACGTGCAA 
                   
               
               
                   
                 AAGAAGCTACCGATCATACGAAAGATCATCATCATGGATAGCAAGACCGACTACCAGGGCTTC 
                   
               
               
                   
                 CAAAGCATGTACACCTTCGTGACTTCCCATTTGCCACCCAGCTTCAACGAGTACGACTTCGTG 
                   
               
               
                   
                 CCCGAGAGCTTCGACCGGGACAAAACCATCGCCCTGATCATGAACAGTAGTGGTAGTACAGGA 
                   
               
               
                   
                 TTACCCAAGGGCGTAGCCCTACCGCACCGCACCGCTTGTGTCCGATTCAGTCATGCCCGCGAC 
                   
               
               
                   
                 CCCATCTTCGGCTACCAGAACATCCCCGACACCGCTATCCTCAGCGTGGTGCCATTTCACCAC 
                   
               
               
                   
                 GGCTTCGGCATGTTCACCACGCTGGGCTACTTGATCTGCGGCTTTCGGGTCGTGCTCATGTAC 
                   
               
               
                   
                 CGCTTCGAGGAGGAGCTATTCTTGCGCAGCTTGCAAGACTATAAGATTCAATCTGCCCTGCTG 
                   
               
               
                   
                 GTGCCCACACTATTTAGCTGCCTCGCTAAGAGCACTCTCATCGACAAGTACGACCTAAGCAGC 
                   
               
               
                   
                 TTGCGCGAGATCGCCAGCGGCGGGGCGCCGCTCAGCAAGGAGGTAGGTGAGGCCGTGGCCAAA 
                   
               
               
                   
                 CGCTTCCGCCTACCAGGCATCCGCCAGGGCTATGGCCTGACAGAAACAACCAACGCCGTCATG 
                   
               
               
                   
                 ATCACCCCCGAGGGGGACCGTAAGCCTGGCTCAGTAGGCAAGGTGGTGCCCTTCTTCGAGGCT 
                   
               
               
                   
                 AAGGTGGTAGACTTGGTCACCGGTAAGACACTGGGTGTGAACCAGCGCGGTGAGCTGTGCGTC 
                   
               
               
                   
                 CGTGGCCCCATGATCATGAGCGGCTACGTTAACAACCCCGAGGCTACGAACGCTCTCATCGAC 
                   
               
               
                   
                 AAGGACGGCTGGCTGCACAGCGGCGACATCGCCTACTGGGACGAGGACGAGCACTTCTTCATC 
                   
               
               
                   
                 GTGGACCGGCTGAAGAGCCTGATCAAATACAAGGGCTACCAGGTAGCCCCAGCCGAACTGGAG 
                   
               
               
                   
                 GGCATCCTGCTGCAACACCCCTACATCTTCGACGCCGGAGTCGCCGGCCTGCCCGACGACGAT 
                   
               
               
                   
                 GCCGGCGAGCTGCCCGCCGCAGTCGTCGTGTTGGAACACGGTAAAACCATGACCGAGAAAGAG 
                   
               
               
                   
                 ATCGTGGACTATGTGGCCAGCCAGGTTACAACCGCCAAGAAGCTGCGCGGTGGTGTTGTGTTT 
                   
               
               
                   
                 GTGGATGAAGTCCCTAGAGGATCGACCGGCAAGTTAGACGCCCGCAAGATCCGCGAGATTCTC 
                   
               
               
                   
                 ACTAAGGCCAAGAAGGACGGCAAGATCGCCGTGGGTGGTGGTGGTTCTATCAACATAACTGTG 
                   
               
               
                   
                 GGCTGTGGGAATGATTTCAAGGAATCCACTATCCATACCCAGGGCTGCGTGGAGACTATAGCA 
                   
               
               
                   
                 ATATGGCTAAGGAAGAACATACTGCTGGTGGCTGCAGCGGCCCTGGGCATTGCTTTTGTGGAG 
                   
               
               
                   
                 GTCTTGGGAATTATCTTCTCCTGCTGTCTGGTGAAGAGTATTCGAAGTGGCTATGAAGTAATG 
                   
               
               
                   
                 TAG 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
               
             
               
                 TABLE 14 
               
               
                   
               
               
                   
                   
                 SEQ 
               
               
                   
                   
                 ID  
               
               
                   
                 Sequence 
                 NO: 
               
               
                   
               
             
            
               
                 Signal  
                 
                   MSRSVALAVLALLSLSGLEA 
                 
                 121 
               
               
                 peptide 
                 
                   ATGTCTCGCTCCGTGGCCTTAGCTGTGCTCGCGCTACTCTCTCTTTCTGGCCTGGAGGCT 
                 
                 122 
               
               
                 of hβ 2   
                   
                   
               
               
                 micro- 
                   
                   
               
               
                 globulin 
                   
                   
               
               
                   
               
               
                 SARS- 
                 KLWAQCVQL 
                 141 
               
               
                 CoV2 
                 AAACTGTGGGCCCAGTGTGTGCAGCTG 
                 142 
               
               
                 peptide  
                   
                   
               
               
                 1 (for  
                   
                   
               
               
                 MHC  
                   
                   
               
               
                 class I 
                   
                   
               
               
                 molecule) 
                   
                   
               
               
                   
               
               
                 Peptide  
                 GGGASGGGGSGGGGS 
                   5 
               
               
                 linker 1 
                 GGCGGAGGTGCCTCTGGCGGTGGGGGCAGCGGTGGAGGGGGCAGT 
                   6 
               
               
                   
               
               
                 hβ 2   
                 IQRTPKIQVYSRHPAENGKSNFLNCYVSGFHPSDIEVDLLKNGERIEKVEHSDLSFSKDWSFY 
                 121 
               
               
                 Micro- 
                 LLYYTEFTPTEKDEYACRVNHVTLSQPKIVKWDRDM 
                   
               
               
                 globulin 
                 ATCCAGCGTACTCCAAAGATTCAGGTTTACTCACGTCATCCAGCAGAGAATGGAAAGTCAAAT 
                 122 
               
               
                 (from  
                 TTCCTGAATTGCTATGTGTCTGGGTTTCATCCATCCGACATTGAAGTTGACTTACTGAAGAAT 
                   
               
               
                 which 
                 GGAGAGAGAATTGAAAAAGTGGAGCATTCAGACTTGTCTTTCAGCAAGGACTGGTCTTTCTAT 
                   
               
               
                 signal  
                 CTCTTGTACTACACTGAATTCACCCCCACTGAAAAAGATGAGTATGCCTGCCGTGTGAACCAT 
                   
               
               
                 peptide 
                 GTGACTTTGTCACAGCCCAAGATAGTTAAGTGGGATCGAGACATG 
                   
               
               
                 is  
                   
                   
               
               
                 removed) 
                   
                   
               
               
                   
               
               
                 hMHC  
                 GSHSMRYFFTSVSRPGRGEPRFIAVGYVDDTQFVRFDSDAASQRMEPRAPWIEQEGPEYWDGE 
                 143 
               
               
                 class I 
                 TRKVKAHSQTHRVDLGTLRGYYNQSEAGSHTVQRMYGCDVGSDWRFLRGYHQYAYDGKDYIAL 
                   
               
               
                 (HLA- 
                 KEDLRSWTAADMAAQTTKHKWEAAHVAEQLRAYLEGTCVEWLRRYLENGKETLQRTDAPKTHM 
                   
               
               
                 A0201) 
                 THHAVSDHEATLRCWALSFYPAEITLTWQRDGEDQTQDTELVETRPAGDGTFQKWAAVVVPSG 
                   
               
               
                 α chain 
                 QEQRYTCHVQHEGLPKPLTLRWEPSSQPTIPIVGIIAGLVLFGAVITGAVVAAVMWRRKSSDR 
                   
               
               
                 (from  
                 KGGSYSQAASSDSAQGSDVSLTACKV 
                   
               
               
                 which  
                 GGCTCTCACTCCATGAGGTATTTCTTCACATCCGTGTCCCGGCCCGGCCGCGGGGAGCCCCGC 
                 144 
               
               
                 signal  
                 TTCATCGCAGTGGGCTACGTGGACGACACGCAGTTCGTGCGGTTCGACAGCGACGCCGCGAGC 
                   
               
               
                 peptide 
                 CAGAGGATGGAGCCGCGGGCGCCGTGGATAGAGCAGGAGGGTCCGGAGTATTGGGACGGGGAG 
                   
               
               
                 is 
                 ACACGGAAAGTGAAGGCCCACTCACAGACTCACCGAGTGGACCTGGGGACCCTGCGCGGCTAC 
                   
               
               
                 removed) 
                 TACAACCAGAGCGAGGCCGGTTCTCACACCGTCCAGAGGATGTATGGCTGCGACGTGGGGTCG 
                   
               
               
                   
                 GACTGGCGCTTCCTCCGCGGGTACCACCAGTACGCCTACGACGGCAAGGATTACATCGCCCTG 
                   
               
               
                   
                 AAAGAGGACCTGCGCTCTTGGACCGCGGCGGACATGGCAGCTCAGACCACCAAGCACAAGTGG 
                   
               
               
                   
                 GAGGCGGCCCATGTGGCGGAGCAGTTGAGAGCCTACCTGGAGGGCACGTGCGTGGAGTGGCTC 
                   
               
               
                   
                 CGCAGATACCTGGAGAACGGGAAGGAGACGCTGCAGCGCACGGACGCCCCCAAAACGCATATG 
                   
               
               
                   
                 ACTCACCACGCTGTCTCTGACCATGAAGCCACCCTGAGGTGCTGGGCCCTGAGCTTCTACCCT 
                   
               
               
                   
                 GCGGAGATCACACTGACCTGGCAGCGGGATGGGGAGGACCAGACCCAGGACACGGAGCTCGTG 
                   
               
               
                   
                 GAGACCAGGCCTGCAGGGGATGGAACCTTCCAGAAGTGGGCGGCTGTGGTGGTGCCTTCTGGA 
                   
               
               
                   
                 CAGGAGCAGAGATACACCTGCCATGTGCAGCATGAGGGTTTGCCCAAGCCCCTCACCCTGAGA 
                   
               
               
                   
                 TGGGAGCCGTCTTCCCAGCCCACCATCCCCATCGTGGGCATCATTGCTGGCCTGGTTCTCTTT 
                   
               
               
                   
                 GGAGCTGTGATCACTGGAGCTGTGGTCGCTGCTGTGATGTGGAGGAGGAAGAGCTCAGATAGA 
                   
               
               
                   
                 AAAGGAGGGAGCTACTCTCAGGCTGCAAGCAGTGACAGTGCCCAGGGCTCTGATGTGTCTCTC 
                   
               
               
                   
                 ACAGCTTGTAAAGTG 
                   
               
               
                   
               
               
                 Peptide  
                 GGGGSGGGGSGGGGSGGGGS 
                  11 
               
               
                 linker 2 
                 GGGGGGGGAGGCTCCGGTGGAGGGGGGTCTGGAGGGGGGGGGTCTGGTGGAGGCGGAAGT 
                  12 
               
               
                   
               
               
                 h single 
                 IQRTPKIQVYSRHPAENGKSNFLNCYVSGFUPSDIEVDLLKNGERIEKVEHSDLSFSKDWSFY 
                 145 
               
               
                 chain 
                 LLYYTEFTPTEKDEYACRVNHVTLSQPKIVKWDRDMGGGGSGGGGSGGGGSGGGGSGSHSMRY 
                   
               
               
                 MHC  
                 FFTSVSRPGRGEPRFIAVGYVDDTQFVRFDSDAASQRMEPRAPWIEQEGPEYWDGETRKVKAH 
                   
               
               
                 class I 
                 SQTHRVDLGTLRGYYNQSEAGSHTVQRMYGCDVGSDWRFLRGYHQYAYDGK 
                   
               
               
                 molecule 
                 DYIALKEDLRSWTAADMAAQTTKHKWEAAHVAEQLRAYLEGTCVEWLRRYLENGKETLQRTDA 
                   
               
               
                 (β 2   
                 PKTHMTHHAVSDHEATLRCWALSFYPAEITLTWQRDGEDQTQDTELVETRPAGDGTFQKWAAV 
                   
               
               
                 micro- 
                 VVPSGQEQRYTCHVQHEGLPKPLTLRWEPSSQPTIPIVGIIAGLVLFGAVITGAVVAAVMWRR 
                   
               
               
                 globulin 
                 KSSDRKGGSYSQAASSDSAQGSDVSLTACKV 
                   
               
               
                 (from  
                 ATCCAGCGTACTCCAAAGATTCAGGTTTACTCACGTCATCCAGCAGAGAATGGAAAGTCAAAT 
                 146 
               
               
                 which 
                 TTCCTGAATTGCTATGTGTCTGGGTTTCATCCATCCGACATTGAAGTTGACTTACTGAAGAAT 
                   
               
               
                 signal  
                 GGAGAGAGAATTGAAAAAGTGGAGCATTCAGACTTGTCTTTCAGCAAGGACTGGTCTTTCTAT 
                   
               
               
                 peptide 
                 CTCTTGTACTACACTGAATTCACCCCCACTGAAAAAGATGAGTATGCCTGCCGTGTGAACCAT 
                   
               
               
                 is re- 
                 GTGACTTTGTCACAGCCCAAGATAGTTAAGTGGGATCGAGACATGGGAGGCGGCGGGTCTGGC 
                   
               
               
                 moved) + 
                 GGCGGCGGCAGTGGCGGTGGCGGTAGCGGCGGAGGTGGATCTGGCTCTCACTCCATGAGGTAT 
                   
               
               
                 peptide  
                 TTCTTCACATCCGTGTCCCGGCCCGGCCGCGGGGAGCCCCGCTTCATCGCAGTGGGCTACGTG 
                   
               
               
                 linker 
                 GACGACACGCAGTTCGTGCGGTTCGACAGCGACGCCGCGAGCCAGAGGATGGAGCCGCGGGCG 
                   
               
               
                 2 + MHC  
                 CCGTGGATAGAGCAGGAGGGTCCGGAGTATTGGGACGGGGAGACACGGAAAGTGAAGGCCCAC 
                   
               
               
                 class I 
                 TCACAGACTCACCGAGTGGACCTGGGGACCCTGCGCGGCTACTACAACCAGAGCGAGGCCGGT 
                   
               
               
                 (HLA- 
                 TCTCACACCGTCCAGAGGATGTATGGCTGCGACGTGGGGTCGGACTGGCGCTTCCTCCGCGGG 
                   
               
               
                 A0201) 
                 TACCACCAGTACGCCTACGACGGCAAGGATTACATCGCCCTGAAAGAGGACCTGCGCTCTTGG 
                   
               
               
                 α chain 
                 ACCGCGGCGGACATGGCAGCTCAGACCACCAAGCACAAGTGGGAGGCGGCCCATGTGGCGGAG 
                   
               
               
                 (from  
                 CAGTTGAGAGCCTACCTGGAGGGCACGTGCGTGGAGTGGCTCCGCAGATACCTGGAGAACGGG 
                   
               
               
                 which 
                 AAGGAGACGCTGCAGCGCACGGACGCCCCCAAAACGCATATGACTCACCACGCTGTCTCTGAC 
                   
               
               
                 signal  
                 CATGAAGCCACCCTGAGGTGCTGGGCCCTGAGCTTCTACCCTGCGGAGATCACACTGACCTGG 
                   
               
               
                 peptide 
                 CAGCGGGATGGGGAGGACCAGACCCAGGACACGGAGCTCGTGGAGACCAGGCCTGCAGGGGAT 
                   
               
               
                 is  
                 GGAACCTTCCAGAAGTGGGCGGCTGTGGTGGTGCCTTCTGGACAGGAGCAGAGATACACCTGC 
                   
               
               
                 removed)) 
                 CATGTGCAGCATGAGGGTTTGCCCAAGCCCCTCACCCTGAGATGGGAGCCGTCTTCCCAGCCC 
                   
               
               
                   
                 ACCATCCCCATCGTGGGCATCATTGCTGGCCTGGTTCTCTTTGGAGCTGTGATCACTGGAGCT 
                   
               
               
                   
                 GTGGTCGCTGCTGTGATGTGGAGGAGGAAGAGCTCAGATAGAAAAGGAGGGAGCTACTCTCAG 
                   
               
               
                   
                 GCTGCAAGCAGTGACAGTGCCCAGGGCTCTGATGTGTCTCTCACAGCTTGTAAAGTG 
                   
               
               
                   
               
               
                 hsc- 
                   MSRSVALAVLALLSLSGLE AKLWAQCVQLGGGASGGGGSGGGGSIQRTPKIQVYSRHPAENGK 
                 147 
               
               
                 Trimer 
                 SNFLNCYVSGFHPSDIEVDLLKNGERIEKVEHSDLSFSKDWSFYLLYYTEFTPTEKDEYACRV 
                   
               
               
                 (SARS- 
                 NHVTLSQPKIVKWDRDMGGGGSGGGGSGGGGSGGGGSGSHSMRYFFTSVSRPGRGEPRFIAVG 
                   
               
               
                 CoV2 
                 YVDDTQFVRFDSDAASQRMEPRAPWIEQEGPEYWDGETRKVKAHSQTHRVDLGTLRGYYNQSE 
                   
               
               
                 peptide  
                 AGSHTVQRMYGCDVGSDWRFLRGYHQYAYDGKDYIALKEDLRSWTAADMAAQTTKHKWEAAHV 
                   
               
               
                 1 + 
                 AEQLRAYLEGTCVEWLRRYLENGKETLQRTDAPKTHMTHHAVSDHEATLRCWALSFYPAEITL 
                   
               
               
                 peptide  
                 TWQRDGEDQTQDTELVETRPAGDGTFQKWAAVVVPSGQEQRYTCHVQHEGLPKPLTLRWEPSS 
                   
               
               
                 linker 
                 QPTIPIVGIIAGLVLFGAVITGAVVAAVMWRRKSSDRKGGSYSQAASSDSAQGSDVSLTACKV 
                   
               
               
                 1 +  
                   ATGTCTCGCTCCGTGGCCTTAGCTGTGCTCGCGCTACTCTCTCTTTCTGGCCTGGAGGCT AAA 
                 148 
               
               
                 single  
                 CTGTGGGCCCAGTGTGTGCAGCTGGGCGGAGGGGCATCAGGCGGCGGTGGGTCAGGTGGAGGT 
                   
               
               
                 chain 
                 GGGAGTATCCAGCGTACTCCAAAGATTCAGGTTTACTCACGTCATCCAGCAGAGAATGGAAAG 
                   
               
               
                 MHC 
                 TCAAATTTCCTGAATTGCTATGTGTCTGGGTTTCATCCATCCGACATTGAAGTTGACTTACTG 
                   
               
               
                 class I 
                 AAGAATGGAGAGAGAATTGAAAAAGTGGAGCATTCAGACTTGTCTTTCAGCAAGGACTGGTCT 
                   
               
               
                 (HLA- 
                 TTCTATCTCTTGTACTACACTGAATTCACCCCCACTGAAAAAGATGAGTATGCCTGCCGTGTG 
                   
               
               
                 A0201) 
                 AACCATGTGACTTTGTCACAGCCCAAGATAGTTAAGTGGGATCGAGACATGGGAGGCGGCGGG 
                   
               
               
                 molecule) 
                 TCTGGCGGCGGCGGCAGTGGCGGTGGCGGTAGCGGCGGAGGTGGATCTGGCTCTCACTCCATG 
                   
               
               
                   
                 AGGTATTTCTTCACATCCGTGTCCCGGCCCGGCCGCGGGGAGCCCCGCTTCATCGCAGTGGGC 
                   
               
               
                   
                 TACGTGGACGACACGCAGTTCGTGCGGTTCGACAGCGACGCCGCGAGCCAGAGGATGGAGCCG 
                   
               
               
                   
                 CGGGCGCCGTGGATAGAGCAGGAGGGTCCGGAGTATTGGGACGGGGAGACACGGAAAGTGAAG 
                   
               
               
                   
                 GCCCACTCACAGACTCACCGAGTGGACCTGGGGACCCTGCGCGGCTACTACAACCAGAGCGAG 
                   
               
               
                   
                 GCCGGTTCTCACACCGTCCAGAGGATGTATGGCTGCGACGTGGGGTCGGACTGGCGCTTCCTC 
                   
               
               
                   
                 CGCGGGTACCACCAGTACGCCTACGACGGCAAGGATTACATCGCCCTGAAAGAGGACCTGCGC 
                   
               
               
                   
                 TCTTGGACCGCGGCGGACATGGCAGCTCAGACCACCAAGCACAAGTGGGAGGCGGCCCATGTG 
                   
               
               
                   
                 GCGGAGCAGTTGAGAGCCTACCTGGAGGGCACGTGCGTGGAGTGGCTCCGCAGATACCTGGAG 
                   
               
               
                   
                 AACGGGAAGGAGACGCTGCAGCGCACGGACGCCCCCAAAACGCATATGACTCACCACGCTGTC 
                   
               
               
                   
                 TCTGACCATGAAGCCACCCTGAGGTGCTGGGCCCTGAGCTTCTACCCTGCGGAGATCACACTG 
                   
               
               
                   
                 ACCTGGCAGCGGGATGGGGAGGACCAGACCCAGGACACGGAGCTCGTGGAGACCAGGCCTGCA 
                   
               
               
                   
                 GGGGATGGAACCTTCCAGAAGTGGGCGGCTGTGGTGGTGCCTTCTGGACAGGAGCAGAGATAC 
                   
               
               
                   
                 ACCTGCCATGTGCAGCATGAGGGTTTGCCCAAGCCCCTCACCCTGAGATGGGAGCCGTCTTCC 
                   
               
               
                   
                 CAGCCCACCATCCCCATCGTGGGCATCATTGCTGGCCTGGTTCTCTTTGGAGCTGTGATCACT 
                   
               
               
                   
                 GGAGCTGTGGTCGCTGCTGTGATGTGGAGGAGGAAGAGCTCAGATAGAAAAGGAGGGAGCTAC 
                   
               
               
                   
                 TCTCAGGCTGCAAGCAGTGACAGTGCCCAGGGCTCTGATGTGTCTCTCACAGCTTGTAAAGTG 
                   
               
               
                   
               
               
                 hCD81 
                 MGVEGCTKCIKYLLFVFNFVFWLAGGVILGVALWLRHDPQTTNLLYLELGDKPAPNTFYVGIY 
                 129 
               
               
                   
                 ILIAVGAVMMFVGFLGCYGAIQESQCLLGTFFTCLVILFACEVAAGIWGFVNKDQIAKDVKQF 
                   
               
               
                   
                 YDQALQQAVVDDDANNAKAVVKTFHETLDCCGSSTLTALTTSVLKNNLCPSGSNIISNLFKED 
                   
               
               
                   
                 CHQKIDDLFSGKLYLIGIAAIVVAVIMIFEMILSMVLCCGIRNSSVY 
                   
               
               
                   
                 ATGGGAGTGGAGGGCTGCACCAAGTGCATCAAGTACCTGCTCTTCGTCTTCAATTTCGTCTTC 
                 130 
               
               
                   
                 TGGCTGGCTGGAGGCGTGATCCTGGGTGTGGCCCTGTGGCTCCGCCATGACCCGCAGACCACC 
                   
               
               
                   
                 AACCTCCTGTATCTGGAGCTGGGAGACAAGCCCGCGCCCAACACCTTCTATGTAGGCATCTAC 
                   
               
               
                   
                 ATCCTCATCGCTGTGGGCGCTGTCATGATGTTCGTTGGCTTCCTGGGCTGCTACGGGGCCATC 
                   
               
               
                   
                 CAGGAATCCCAGTGCCTGCTGGGGACGTTCTTCACCTGCCTGGTCATCCTGTTTGCCTGTGAG 
                   
               
               
                   
                 GTGGCCGCCGGCATCTGGGGCTTTGTCAACAAGGACCAGATCGCCAAGGATGTGAAGCAGTTC 
                   
               
               
                   
                 TATGACCAGGCCCTACAGCAGGCCGTGGTGGATGATGACGCCAACAACGCCAAGGCTGTGGTG 
                   
               
               
                   
                 AAGACCTTCCACGAGACGCTTGACTGCTGTGGCTCCAGCACACTGACTGCTTTGACCACCTCA 
                   
               
               
                   
                 GTGCTCAAGAACAATTTGTGTCCCTCGGGCAGCAACATCATCAGCAACCTCTTCAAGGAGGAC 
                   
               
               
                   
                 TGCCACCAGAAGATCGATGACCTCTTCTCCGGGAAGCTGTACCTCATCGGCATTGCTGCCATC 
                   
               
               
                   
                 GTGGTCGCTGTGATCATGATCTTCGAGATGATCCTGAGCATGGTGCTGTGCTGTGGCATCCGG 
                   
               
               
                   
                 AACAGCTCCGTGTACTGA 
                   
               
               
                   
               
               
                 hsc-    
                   MSRSVALAVLALLSLSGLEA KLWAQCVQLGGGASGGGGSGGGGSIQRTPKIQVYSRHPAENGK 
                 149 
               
               
                 Trimer- 
                 SNFLNCYVSGFHPSDIEVDLLKNGERIEKVEHSDLSFSKDWSFYLLYYTEFTPTEKDEYACRV 
                   
               
               
                 CD81 
                 NHVTLSQPKIVKWDRDMGGGGSGGGGSGGGGSGGGGSGSHSMRYFFTSVSRPGRGEPRFIAVG 
                   
               
               
                 (SARS- 
                 YVDDTQFVRFDSDAASQRMEPRAPWIEQEGPEYWDGETRKVKAHSQTHRVDLGTLRGYYNQSE 
                   
               
               
                 CoV2 sc- 
                 AGSHTVQRMYGCDVGSDWRFLRGYHQYAYDGKDYIALKEDLRSWTAADMAAQTTKHKWEAAHV 
                   
               
               
                 Trimer + 
                 AEQLRAYLEGTCVEWLRRYLENGKETLQRTDAPKTHMTHHAVSDHEATLRCWALSFYPAEITL 
                   
               
               
                 CD81) 
                 TWQRDGEDQTQDTELVETRPAGDGTFQKWAAVVVPSGQEQRYTCHVQHEGLPKPLTLRWEPSS 
                   
               
               
                   
                 QPTIPIVGIIAGLVLFGAVITGAVVAAVMWRRKSSDRKGGSYSQAASSDSAQGSDVSLTACKV 
                   
               
               
                   
                 MGVEGCTKCIKYLLFVFNFVFWLAGGVILGVALWLRHDPQTTNLLYLELGDKPAPNTFYVGIY 
                   
               
               
                   
                 ILIAVGAVMMFVGFLGCYGAIQESQCLLGTFFTCLVILFACEVAAGIWGFVNKDQIAKDVKQF 
                   
               
               
                   
                 YDQALQQAVVDDDANNAKAVVKTFHETLDCCGSSTLTALTTSVLKNNLCPSGSNIISNLFKED 
                   
               
               
                   
                 CHQKIDDLFSGKLYLIGIAAIVVAVIMIFEMILSMVLCCGIRNSSVY 
                   
               
               
                   
                   ATGTCTCGCTCCGTGGCCTTAGCTGTGCTCGCGCTACTCTCTCTTTCTGGCCTGGAGGCT AAA 
                 150 
               
               
                   
                 CTGTGGGCCCAGTGTGTGCAGCTGGGCGGAGGGGCATCAGGCGGCGGTGGGTCAGGTGGAGGT 
                   
               
               
                   
                 GGGAGTATCCAGCGTACTCCAAAGATTCAGGTTTACTCACGTCATCCAGCAGAGAATGGAAAG 
                   
               
               
                   
                 TCAAATTTCCTGAATTGCTATGTGTCTGGGTTTCATCCATCCGACATTGAAGTTGACTTACTG 
                   
               
               
                   
                 AAGAATGGAGAGAGAATTGAAAAAGTGGAGCATTCAGACTTGTCTTTCAGCAAGGACTGGTCT 
                   
               
               
                   
                 TTCTATCTCTTGTACTACACTGAATTCACCCCCACTGAAAAAGATGAGTATGCCTGCCGTGTG 
                   
               
               
                   
                 AACCATGTGACTTTGTCACAGCCCAAGATAGTTAAGTGGGATCGAGACATGGGAGGCGGCGGG 
                   
               
               
                   
                 TCTGGCGGCGGCGGCAGTGGCGGTGGCGGTAGCGGCGGAGGTGGATCTGGCTCTCACTCCATG 
                   
               
               
                   
                 AGGTATTTCTTCACATCCGTGTCCCGGCCCGGCCGCGGGGAGCCCCGCTTCATCGCAGTGGGC 
                   
               
               
                   
                 TACGTGGACGACACGCAGTTCGTGCGGTTCGACAGCGACGCCGCGAGCCAGAGGATGGAGCCG 
                   
               
               
                   
                 CGGGCGCCGTGGATAGAGCAGGAGGGTCCGGAGTATTGGGACGGGGAGACACGGAAAGTGAAG 
                   
               
               
                   
                 GCCCACTCACAGACTCACCGAGTGGACCTGGGGACCCTGCGCGGCTACTACAACCAGAGCGAG 
                   
               
               
                   
                 GCCGGTTCTCACACCGTCCAGAGGATGTATGGCTGCGACGTGGGGTCGGACTGGCGCTTCCTC 
                   
               
               
                   
                 CGCGGGTACCACCAGTACGCCTACGACGGCAAGGATTACATCGCCCTGAAAGAGGACCTGCGC 
                   
               
               
                   
                 TCTTGGACCGCGGCGGACATGGCAGCTCAGACCACCAAGCACAAGTGGGAGGCGGCCCATGTG 
                   
               
               
                   
                 GCGGAGCAGTTGAGAGCCTACCTGGAGGGCACGTGCGTGGAGTGGCTCCGCAGATACCTGGAG 
                   
               
               
                   
                 AACGGGAAGGAGACGCTGCAGCGCACGGACGCCCCCAAAACGCATATGACTCACCACGCTGTC 
                   
               
               
                   
                 TCTGACCATGAAGCCACCCTGAGGTGCTGGGCCCTGAGCTTCTACCCTGCGGAGATCACACTG 
                   
               
               
                   
                 ACCTGGCAGCGGGATGGGGAGGACCAGACCCAGGACACGGAGCTCGTGGAGACCAGGCCTGCA 
                   
               
               
                   
                 GGGGATGGAACCTTCCAGAAGTGGGCGGCTGTGGTGGTGCCTTCTGGACAGGAGCAGAGATAC 
                   
               
               
                   
                 ACCTGCCATGTGCAGCATGAGGGTTTGCCCAAGCCCCTCACCCTGAGATGGGAGCCGTCTTCC 
                   
               
               
                   
                 CAGCCCACCATCCCCATCGTGGGCATCATTGCTGGCCTGGTTCTCTTTGGAGCTGTGATCACT 
                   
               
               
                   
                 GGAGCTGTGGTCGCTGCTGTGATGTGGAGGAGGAAGAGCTCAGATAGAAAAGGAGGGAGCTAC 
                   
               
               
                   
                 TCTCAGGCTGCAAGCAGTGACAGTGCCCAGGGCTCTGATGTGTCTCTCACAGCTTGTAAAGTG 
                   
               
               
                   
                 ATGGGAGTGGAGGGCTGCACCAAGTGCATCAAGTACCTGCTCTTCGTCTTCAATTTCGTCTTC 
                   
               
               
                   
                 TGGCTGGCTGGAGGCGTGATCCTGGGTGTGGCCCTGTGGCTCCGCCATGACCCGCAGACCACC 
                   
               
               
                   
                 AACCTCCTGTATCTGGAGCTGGGAGACAAGCCCGCGCCCAACACCTTCTATGTAGGCATCTAC 
                   
               
               
                   
                 ATCCTCATCGCTGTGGGCGCTGTCATGATGTTCGTTGGCTTCCTGGGCTGCTACGGGGCCATC 
                   
               
               
                   
                 CAGGAATCCCAGTGCCTGCTGGGGACGTTCTTCACCTGCCTGGTCATCCTGTTTGCCTGTGAG 
                   
               
               
                   
                 GTGGCCGCCGGCATCTGGGGCTTTGTCAACAAGGACCAGATCGCCAAGGATGTGAAGCAGTTC 
                   
               
               
                   
                 TATGACCAGGCCCTACAGCAGGCCGTGGTGGATGATGACGCCAACAACGCCAAGGCTGTGGTG 
                   
               
               
                   
                 AAGACCTTCCACGAGACGCTTGACTGCTGTGGCTCCAGCACACTGACTGCTTTGACCACCTCA 
                   
               
               
                   
                 GTGCTCAAGAACAATTTGTGTCCCTCGGGCAGCAACATCATCAGCAACCTCTTCAAGGAGGAC 
                   
               
               
                   
                 TGCCACCAGAAGATCGATGACCTCTTCTCCGGGAAGCTGTACCTCATCGGCATTGCTGCCATC 
                   
               
               
                   
                 GTGGTCGCTGTGATCATGATCTTCGAGATGATCCTGAGCATGGTGCTGTGCTGTGGCATCCGG 
                   
               
               
                   
                 AACAGCTCCGTGTACTGA 
               
               
                   
               
            
           
         
       
     
     Preparation of Fetal Bovine Serum from which Exosomes are Removed 
     After 10 mL of inactivated FBS and 2 mL of a 50% poly(ethylene glycol) 10,000 solution (manufactured by Sigma-Aldrich, #81280) were stirred at 4° C. for 2 hours, exosomes were precipitated under centrifugation conditions of 1,500×g, 4° C., and 30 minutes, and supernatant was collected to obtain fetal bovine serum from which the exosomes were removed. 
     [Example 1] Antigen-Presenting Extracellular Vesicles Containing MHC Class I Molecules and T-Cell Stimulatory Cytokines in Membrane 
     HEK293T cells were seeded in a cell culture dish and cultured in a Dulbecco&#39;s modified Eagle medium to which 2% fetal bovine serum and penicillin/streptomycin were added. Cells at about 50% confluence were transfected with two plasmids (pCAG vectors encoding sc-Trimer-CD81 and CD63-IL-2, respectively) at the same time using polyethylenimine “Max” (manufactured by Polysciences Inc.) according to the manufacturer&#39;s instructions. The medium was replaced 3 hours after the transfection, and 24 hours after the transfection, the medium was replaced with a Dulbecco&#39;s modified Eagle medium to which 2% fetal bovine exosomes-removed serum and penicillin/streptomycin were added. 72 hours after the transfection, supernatant was collected, and then the supernatant was centrifuged at 300 g for 5 minutes after being passed through a 0.22 μm filter. Supernatant was collected, and the supernatant was centrifuged at 2,000 g for 20 minutes. A supernatant was collected, and the supernatant was centrifuged at 10,000 g for 30 minutes. Then the supernatant was removed, and pellets were washed with PBS. After PBS was added to the pellets and the pellets were centrifuged at 100,000 g for 2 hours, supernatant was removed, and the pellets suspended in 100 μL of PBS were used as antigen-presenting extracellular vesicles of Example 1 ( FIG.  2 A ). The concentration of the extracellular vesicles was measured according to the manufacturer&#39;s instructions using a BCA protein assay kit (manufactured by Thermo Fisher Scientific Inc.). 
     [Example 2] Antigen-Presenting Extracellular Vesicles Containing MHC Class I Molecules, T-Cell Costimulatory Molecules, and T-Cell Stimulatory Cytokines in Membrane 
     HEK293T cells were seeded in a cell culture dish and cultured in a Dulbecco&#39;s modified Eagle medium to which 2% fetal bovine serum and penicillin/streptomycin were added. Cells at about 50% confluence were transfected with the three plasmids (pCAG vectors encoding sc-Trimer-CD81, CD80-CD9, and CD63-IL-2, respectively) prepared above at the same time using polyethylenimine “Max” (manufactured by Polysciences Inc.) according to the manufacturer&#39;s instructions. The medium was replaced 3 hours after the transfection, and 24 hours after the transfection, the medium was replaced with a Dulbecco&#39;s modified Eagle medium to which 2% fetal bovine exosomes-removed serum and penicillin/streptomycin were added. 72 hours after the transfection, a supernatant was collected, and then the supernatant was centrifuged at 300 g for 5 minutes after being passed through a 0.22 μm filter. A supernatant was collected, and the supernatant was centrifuged at 2,000 g for 20 minutes. A supernatant was collected, and the supernatant was centrifuged at 10,000 g for 30 minutes. After supernatant was collected and the supernatant was centrifuged at 100,000 g for 2 hours, the supernatant was removed, and pellets were washed with PBS. After PBS was added to the pellets and the pellets were centrifuged at 100,000 g for 2 hours, supernatant was removed, and the pellets suspended in 100 μL of PBS were used as antigen-presenting extracellular vesicles of Example 2 ( FIG.  2 B ). The concentration of the antigen-presenting extracellular vesicles was measured according to the manufacturer&#39;s instructions using a BCA protein assay kit (manufactured by Thermo Fisher Scientific Inc.). 
     [Example 3] Antigen-Presenting Extracellular Vesicles 1 Containing MHC Class II Molecules, T-Cell Costimulatory Molecules, and T-Cell Stimulatory Cytokines in Membrane 
     HEK293T cells were seeded in a cell culture dish and cultured in a Dulbecco&#39;s modified Eagle medium to which 2% fetal bovine serum and penicillin/streptomycin were added. Cells at about 50% confluence were transfected with the four plasmids (pCAG vectors encoding sc-Dimer-CD81, an MHC class IIα chain, CD80-CD9, and CD63-IL-2, respectively) prepared above at the same time using polyethylenimine “Max” (manufactured by Polysciences Inc.) according to the manufacturer&#39;s instructions. The medium was replaced 3 hours after the transfection, and 24 hours after the transfection, the medium was replaced with a Dulbecco&#39;s modified Eagle medium to which 2% fetal bovine serum from which exosomes were removed and penicillin/streptomycin were added. 72 hours after the transfection, a supernatant was collected, and then the supernatant was centrifuged at 300 g for 5 minutes after being passed through a 0.22 μm filter. Supernatant was collected, and the supernatant was centrifuged at 2,000 g for 20 minutes. Supernatant was collected, and the supernatant was centrifuged at 10,000 g for 30 minutes. Then, supernatant was removed, and pellets were washed with PBS. After PBS was added to the pellets and the pellets were centrifuged at 100,000 g for 2 hours, supernatant was removed, and the pellets suspended in 100 μL of PBS were used as antigen-presenting extracellular vesicles of Example 3 ( FIG.  2 C ). The concentration of the antigen-presenting extracellular vesicles was measured according to the manufacturer&#39;s instructions using a BCA protein assay kit (manufactured by Thermo Fisher Scientific Inc.). 
     [Example 4] Antigen-Presenting Extracellular Vesicles 2 Containing MHC Class II Molecules, T-Cell Costimulatory Molecules, and T-Cell Stimulatory Cytokines in Membrane 
     HEK293T cells were seeded in a cell culture dish and cultured in a Dulbecco&#39;s modified Eagle medium to which 2% fetal bovine serum and penicillin/streptomycin were added. Cells at about 50% confluence were transfected with five plasmids (pCAG vectors encoding sc-Dimer-CD81, an MHC class IIα chain, CD80-CD9, TGF-β-MFGE8, and CD63-IL-2, respectively) at the same time using polyethylenimine “Max” (manufactured by Polysciences Inc.) according to the manufacturer&#39;s instructions. The medium was replaced 3 hours after the transfection, and 24 hours after the transfection, the medium was replaced with a Dulbecco&#39;s modified Eagle medium to which 2% fetal bovine exosomes-removed serum and penicillin/streptomycin were added. 72 hours after the transfection, supernatant was collected, and then the supernatant was centrifuged at 300 g for 5 minutes after being passed through a 0.22 μm filter. Supernatant was collected, and the supernatant was centrifuged at 2,000 g for 20 minutes. Supernatant was collected, and the supernatant was centrifuged at 10,000 g for 30 minutes. After a supernatant was collected and the supernatant was centrifuged at 100,000 g for 2 hours, the supernatant was removed, and pellets were washed with PBS. After PBS was added to the pellets and the pellets were centrifuged at 100,000 g for 2 hours, supernatant was removed, and the pellets suspended in 100 μL of PBS were used as antigen-presenting extracellular vesicles of Example 4 ( FIG.  2 D ). The concentration of the antigen-presenting extracellular vesicles was measured according to the manufacturer&#39;s instructions using a BCA protein assay kit (manufactured by Thermo Fisher Scientific Inc.). 
     [Example 5] Antigen-Presenting Extracellular Vesicles 3 Containing MHC Class II Molecules, T-Cell Costimulatory Molecules, and T-Cell Stimulatory Cytokines in Membrane 
     HEK293T cells were seeded in a cell culture dish and cultured in a Dulbecco&#39;s modified Eagle medium to which 2% fetal bovine serum and penicillin/streptomycin were added. Cells at about 50% confluence were transfected with the four plasmids (pCAG vectors encoding sc-Dimer-CD81, an MHC class IIα chain, CD80-CD9, and CD81-IL-4, respectively) prepared above at the same time using polyethylenimine “Max” (manufactured by Polysciences Inc.) according to the manufacturer&#39;s instructions. The medium was replaced 3 hours after the transfection, and 24 hours after the transfection, the medium was replaced with a Dulbecco&#39;s modified Eagle medium to which 2% fetal bovine exosomes-removed serum and penicillin/streptomycin were added. 72 hours after the transfection, supernatant was collected, and then the supernatant was centrifuged at 300 g for 5 minutes after being passed through a 0.22 μm filter. Supernatant was collected, and the supernatant was centrifuged at 2,000 g for 20 minutes. Supernatant was collected, and the supernatant was centrifuged at 10,000 g for 30 minutes. After supernatant was collected and the supernatant was centrifuged at 100,000 g for 2 hours, the supernatant was removed, and pellets were washed with PBS. After PBS was added to the pellets and the pellets were centrifuged at 100,000 g for 2 hours, a supernatant was removed, and the pellets suspended in 100 μL of PBS were used as antigen-presenting extracellular vesicles of Example 5 ( FIG.  2 E ). The concentration of the antigen-presenting extracellular vesicles was measured according to the manufacturer&#39;s instructions using a BCA protein assay kit (manufactured by Thermo Fisher Scientific Inc.). 
     [Reference Example 1] Control Extracellular Vesicles 
     HEK293T cells were seeded in a cell culture dish and cultured in a Dulbecco&#39;s modified Eagle medium to which 2% fetal bovine serum and penicillin/streptomycin were added. The medium was replaced with cells at about 50% confluence, and after 24 hours, the medium was replaced with a Dulbecco&#39;s modified Eagle medium to which 2% fetal bovine exosomes-removed serum and penicillin/streptomycin were added. 48 hours after the replacement with the medium from which exosomes were removed, supernatant was collected, and then the supernatant was centrifuged at 300 g for 5 minutes after being passed through a 0.22 μm filter. Supernatant was collected, and the supernatant was centrifuged at 2,000 g for 20 minutes. Supernatant was collected, and the supernatant was centrifuged at 10,000 g for 30 minutes. After a supernatant was collected and the supernatant was centrifuged at 100,000 g for 2 hours, the supernatant was removed, and pellets were washed with PBS. After PBS was added to the pellets and the pellets were centrifuged at 100,000 g for 2 hours, a supernatant was removed, and the pellets suspended in 100 μL of PBS were used as extracellular vesicles of Reference Example 1. The concentration of the antigen-presenting extracellular vesicles was measured according to the manufacturer&#39;s instructions using a BCA protein assay kit (manufactured by Thermo Fisher Scientific Inc.). 
     [Reference Example 2] Extracellular Vesicles Containing MHC Class I Molecules in Membrane 
     HEK293T cells were seeded in a cell culture dish and cultured in a Dulbecco&#39;s modified Eagle medium to which 2% fetal bovine serum and penicillin/streptomycin were added. Cells at about 50% confluence were transfected with a plasmid (a pCAG vector encoding sc-Trimer-CD81) using polyethylenimine “Max” (manufactured by Polysciences Inc.) according to manufacturer&#39;s instructions. The medium was replaced 3 hours after the transfection, and 24 hours after the transfection, the medium was replaced with a Dulbecco&#39;s modified Eagle medium to which 2% fetal bovine exosomes-removed serum and penicillin/streptomycin were added. 0.72 hours after the transfection, supernatant was collected, and then the supernatant was centrifuged at 300 g for 5 minutes after being passed through a 0.22 μm filter. Supernatant was collected, and the supernatant was centrifuged at 2,000 g for 20 minutes. Supernatant was collected, and the supernatant was centrifuged at 10,000 g for 30 minutes. After a supernatant was collected and the supernatant was centrifuged at 100,000 g for 2 hours, the supernatant was removed, and pellets were washed with PBS. After PBS was added to the pellets and the pellets were centrifuged at 100,000 g for 2 hours, supernatant was removed, and the pellets suspended in 100 μL of PBS were used as extracellular vesicles of Reference Example 2. The concentration of the extracellular vesicles was measured according to the manufacturer&#39;s instructions using a BCA protein assay kit (manufactured by Thermo Fisher Scientific Inc.). 
     [Reference Example 3] Extracellular Vesicles Containing T-Cell Costimulatory Molecules in Membrane 
     HEK293T cells were seeded in a cell culture dish and cultured in a Dulbecco&#39;s modified Eagle medium to which 2% fetal bovine serum and penicillin/streptomycin were added. Cells at about 50% confluence were transfected with a plasmid (a pCAG vector encoding CD80-CD9) using polyethylenimine “Max” (manufactured by Polysciences Inc.) according to manufacturer&#39;s instructions. The medium was replaced 3 hours after the transfection, and 24 hours after the transfection, the medium was replaced with a Dulbecco&#39;s modified Eagle medium to which 2% fetal bovine exosomes-removed serum and penicillin/streptomycin were added. 72 hours after the transfection, supernatant was collected, and then the supernatant was centrifuged at 300 g for 5 minutes after being passed through a 0.22 μm filter. Supernatant was collected, and the supernatant was centrifuged at 2,000 g for 20 minutes. Supernatant was collected, and the supernatant was centrifuged at 10,000 g for 30 minutes. After supernatant was collected and the supernatant was centrifuged at 100,000 g for 2 hours, the supernatant was removed, and pellets were washed with PBS. After PBS was added to the pellets and the pellets were centrifuged at 100,000 g for 2 hours, supernatant was removed, and the pellets suspended in 100 μL of PBS were used as extracellular vesicles of Reference Example 3. The concentration of the extracellular vesicles was measured according to the manufacturer&#39;s instructions using a BCA protein assay kit (manufactured by Thermo Fisher Scientific Inc.). 
     [Reference Example 4] Extracellular Vesicles Containing T-Cell Stimulatory Cytokines in Membrane 
     HEK293T cells were seeded in a cell culture dish and cultured in a Dulbecco&#39;s modified Eagle medium to which 2% fetal bovine serum and penicillin/streptomycin were added. Cells at about 50% confluence were transfected with a plasmid (a pCAG vector encoding CD63-IL-2) using polyethylenimine “Max” (Polysciences Inc.) according to manufacturer&#39;s instructions. The medium was replaced 3 hours after the transfection, and 24 hours after the transfection, the medium was replaced with a Dulbecco&#39;s modified Eagle medium to which 2% fetal bovine exosomes-removed serum and penicillin/streptomycin were added. 72 hours after the transfection, supernatant was collected, and then the supernatant was centrifuged at 300 g for 5 minutes after being passed through a 0.22 μm filter. Supernatant was collected, and the supernatant was centrifuged at 2,000 g for 20 minutes. Supernatant was collected, and the supernatant was centrifuged at 10,000 g for 30 minutes. After supernatant was collected and the supernatant was centrifuged at 100,000 g for 2 hours, the supernatant was removed, and pellets were washed with PBS. After PBS was added to the pellets and the pellets were centrifuged at 100,000 g for 2 hours, supernatant was removed, and the pellets suspended in 100 μL of PBS were used as extracellular vesicles of Reference Example 4. The concentration of the extracellular vesicles was measured according to the manufacturer&#39;s instructions using a BCA protein assay kit (manufactured by Thermo Fisher Scientific Inc.). 
     [Reference Example 5] Extracellular Vesicles Containing MHC Class I Molecules and T-Cell Costimulatory Molecules in Membrane 
     HEK293T cells were seeded in a cell culture dish and cultured in a Dulbecco&#39;s modified Eagle medium to which 2% fetal bovine serum and penicillin/streptomycin were added. Cells at about 50% confluence were transfected with two plasmids (pCAG vectors encoding sc-Trimer-CD81 and CD80-CD9, respectively) at the same time using polyethylenimine “Max” (manufactured by Polysciences Inc.) according to the manufacturer&#39;s instructions. The medium was replaced 3 hours after the transfection, and 24 hours after the transfection, the medium was replaced with a Dulbecco&#39;s modified Eagle medium to which 2% fetal bovine exosomes-removed serum and penicillin/streptomycin were added. 72 hours after the transfection, supernatant was collected, and then the supernatant was centrifuged at 300 g for 5 minutes after being passed through a 0.22 μm filter. Supernatant was collected, and the supernatant was centrifuged at 2,000 g for 20 minutes. Supernatant was collected, and the supernatant was centrifuged at 10,000 g for 30 minutes. After a supernatant was collected and the supernatant was centrifuged at 100,000 g for 2 hours, the supernatant was removed, and pellets were washed with PBS. After PBS was added to the pellets and the pellets were centrifuged at 100,000 g for 2 hours, supernatant was removed, and the pellets suspended in 100 μL of PBS were used as extracellular vesicles of Reference Example 5. The concentration of the extracellular vesicles was measured according to the manufacturer&#39;s instructions using a BCA protein assay kit (manufactured by Thermo Fisher Scientific Inc.). 
     Test Example 1-1: Flow Cytometry Analysis of Fusion Protein Contained in Membrane of Extracellular Vesicle 
     The antigen-presenting extracellular vesicles of Example 2 were immunostained by a PS Capture (trademark) exosome flow cytometry kit (manufactured by FUJIFILM Wako Pure Chemical Corporation) according to the manufacturer&#39;s instruction. Antibodies used for staining are as follows (staining time: 15 minutes, temperature: 4° C.). After the staining, expression of each fusion protein was detected with a flow cytometer FACSCantoII (manufactured by BD Biosciences).
         APC-conjugated anti-mouse H-2KbOVA complex antibody (25-D1.16, manufactured by Biolegend, Inc.)   PE-conjugated anti-mouse CD80 antibody (16-10A1, manufactured by Biolegend, Inc.)   Brilliant Violet421-conjugated anti-mouse IL-2 antibody (JES6-5H4, manufactured by Biolegend, Inc.)       

     The results are illustrated in  FIG.  3 A . 
     [Results] 
     From the results of Test Example 1-1, it could be seen that MHC class I molecules presenting OVA antigens, CD80, and IL-2 were contained in the membrane of the antigen-presenting extracellular vesicle of Example 2 ( FIG.  3 A ). 
     Test Example 1-2: Flow Cytometry Analysis of Fusion Protein Contained in Membrane of Extracellular Vesicle 
     The antigen-presenting extracellular vesicles of Example 3 were immunostained by a PS Capture (trademark) exosome flow cytometry kit (manufactured by FUJIFILM Wako Pure Chemical Corporation) according to the manufacturer&#39;s instruction. The antibodies used for the staining are as follows. After the staining, expression of each fusion protein was detected with a flow cytometer FACSCantoII (manufactured by BD Biosciences).
         APC-conjugated anti-mouse IL-2 antibody (JES6-5H4, manufactured by Biolegend, Inc.)   PE-conjugated anti-mouse CD80 antibody (16-10A1, manufactured by Biolegend, Inc.)   APC-Cy7-conjugated anti-mouse I-A/I-E antibody (M5/114.15.2, manufactured by Biolegend, Inc.)       

     The results are illustrated in  FIG.  3 B . 
     [Results] 
     From the results of Test Example 1-2, it could be seen that MHC class II molecules presenting OVA antigens, CD80, and IL-2 were contained in the membrane of the antigen-presenting extracellular vesicle of Example 3 ( FIG.  3 B ). 
     Test Example 1-3: Flow Cytometry Analysis of Fusion Protein Contained in Membrane of Extracellular Vesicle 
     The antigen-presenting extracellular vesicles of Example 4 were immunostained by a PS Capture (trademark) exosome flow cytometry kit (manufactured by FUJIFILM Wako Pure Chemical Corporation) according to the manufacturer&#39;s instruction. The antibodies used for the staining are as follows. After the staining, expression of each fusion protein was detected with a flow cytometer FACSCantoII (manufactured by BD Biosciences).
         APC-conjugated anti-mouse IL-2 antibody (JES6-5H4, manufactured by Biolegend, Inc.)   PE-conjugated anti-mouse CD80 antibody (16-10A1, manufactured by Biolegend, Inc.)   APC-Cy7-conjugated anti-mouse I-A/I-E antibody (M5/114.15.2, manufactured by Biolegend, Inc.)   APC-conjugated anti-mouse LAP (TGF-β1) antibody (TW7-16B4, manufactured by Biolegend, Inc.)       

     The results are illustrated in  FIG.  3 C . 
     [Results] 
     From the results of Test Example 1-3, it could be seen that MHC class II molecules presenting OVA antigens, CD80, IL-2, and TGF-β1 were contained in the membrane of the antigen-presenting extracellular vesicle of Example 4 ( FIG.  3 C ). 
     Test Example 1-4: Flow Cytometry Analysis of Fusion Protein Contained in Membrane of Extracellular Vesicle 
     The antigen-presenting extracellular vesicles of Example 5 were immunostained by a PS Capture (trademark) exosome flow cytometry kit (manufactured by FUJIFILM Wako Pure Chemical Corporation) according to the manufacturer&#39;s instruction. The antibodies used for the staining are as follows. After the staining, expression of each fusion protein was detected with a flow cytometer FACSCantoII (manufactured by BD Biosciences).
         Alexa Fluor 488-conjugated anti-mouse IL-4 antibody (11B11, manufactured by Biolegend, Inc.)   PE-conjugated anti-mouse CD80 antibody (16-10A1, manufactured by Biolegend, Inc.)   APC-Cy7-conjugated anti-mouse I-A/I-E antibody (M5/114.15.2, manufactured by Biolegend, Inc.)       

     The results are illustrated in  FIG.  3 D . 
     [Results] 
     From the results of Test Example 1-4, it could be seen that MHC class II molecules presenting OVA antigens, CD80, and IL-4 were contained in the membrane of the antigen-presenting extracellular vesicle of Example 5 ( FIG.  3 D ). 
     Test Example 2: Experiment on Activation of OVA-Specific CD8-Positive T Cells (OT-1 T Cells) In Vitro by Antigen-Presenting Extracellular Vesicles 
     The following test was conducted in vitro to determine whether the antigen-presenting extracellular vesicles activate antigen-specific CD8-positive T cells. 
     Lymph nodes extracted from an OT-1 mouse, which was an OVA-reactive TCR transgenic mouse, were disrupted on a 100 μm filter to obtain a lymph node cell suspension. The cell suspension was stained using CellTrace Violet (manufactured by Thermo Fisher Scientific Inc.) as a cell proliferation assay reagent according to the manufacturer&#39;s instructions. 2×10 5  stained lymph node cells were suspended in 200 μL of an RPMI1640 medium to which 10% fetal bovine serum, 50 μM 2-mercaptoethanol, and penicillin/streptomycin were added, the antigen-presenting extracellular vesicles of Example 1 or 2 (final concentration: 3 μg/mL), a mixture of three types of the extracellular vesicles of Reference Examples 2 to 4 (final concentration of each of the three types of the extracellular vesicles: 3 μg/mL), or the extracellular vesicles of Reference Examples 1, 2, or 5 (final concentration: 3 μg/mL) were added, culture was performed in a 96 well round bottom plate for 3 days, and then, immunostaining was performed. Antibodies used for staining are as follows (staining time: 15 minutes, temperature: 4° C.). After the staining, a luminescence intensity of CellTrace Violet as a cell proliferation assay reagent in the OT-1 T cells was detected with a flow cytometer FACSCantoII (manufactured by BD Biosciences).
         APC-conjugated anti-mouse CD8 antibody (53-6.7, manufactured by Biolegend, Inc.)   PE-conjugated anti-mouse TCR Vb5.1, 5.2 antibody (MR9-4, manufactured by Biolegend, Inc.)       

     The results are illustrated in  FIG.  4   . 
     [Results] 
     From the results of Test Example 2, it was confirmed that the antigen-presenting extracellular vesicles of Examples 1 and 2 remarkably differentiated and/or proliferated antigen-specific CD8-positive T cells in comparison with the mixture of the three types of the extracellular vesicles of Reference Examples 2 to 4 or the extracellular vesicles of Reference Examples 1, 2, and 5 ( FIG.  4   ). 
     Test Example 3: Experiment on Activation of OVA-Specific CD8-Positive T Cells (OT-1 T Cells) In Vivo by Antigen-Presenting Extracellular Vesicles 
     The following test was conducted in vivo to determine whether the antigen-presenting extracellular vesicles activate antigen-specific CD8-positive T cells. 
     Lymph nodes were extracted from an OT-1 mouse, which was OVA-reactive TCR transgenic mouse, and the same lymphocyte suspension as that of Test Example 2 was prepared. Lymph nodes were similarly extracted from a CD45.1 congenic mouse, and a lymphocyte suspension was prepared. The respective lymphocyte suspensions were mixed at a ratio of 1:1, and the mixture was stained using CellTrace Violet as a cell proliferation assay reagent. 1×10 7  CellTrace Violet-stained mixed lymphocyte suspension suspended in PBS was transferred from the tail vein of the CD45.1/CD45.2 congenic mouse. The next day, a mixture (IL-2/anti-IL-2 antibody complex) of 50 μg of the antigen-presenting extracellular vesicles of Example 2 or the extracellular vesicles of Reference Example 1, or 1.5 μg of IL-2 (manufactured by Biolegend, Inc.) and 50 μg of anti-mouse IL-2 antibodies (S4B6-1, manufactured by Bio X Cell) was transferred to from the tail vein into a CD45.1/CD45.2 congenic mouse. 4 days after cell transfer, lymph nodes were extracted from the recipient mouse, and a lymphocyte suspension was prepared and immunostained. Antibodies used for staining are as follows (staining time: 15 minutes, temperature: 4° C.). After the staining, a luminescence intensity of CellTrace Violet as a cell proliferation assay reagent in the transferred OT-1 T cells and wild-type CD8T cells was detected with a flow cytometer FACSCantoII (manufactured by BD Biosciences).
         PE-Cy7-conjugated anti-mouse CD8 antibody (53-6.7, manufactured by Biolegend, Inc.)   PE-conjugated anti-mouse TCR Vb5.1, 5.2 antibody (MR9-4, manufactured by Biolegend, Inc.)   FITC-conjugated anti-mouse CD45.1 antibody (A20, manufactured by Biolegend, Inc.)   APC-conjugated anti-mouse CD45.2 antibody (104, manufactured by Biolegend, Inc.)       

     The results are illustrated in  FIG.  5   . 
     [Results] 
     From the results of Test Example 3, it could be seen that the antigen-presenting extracellular vesicles of Example 2 hardly activated other CD8-positive T cells (antigen-non-specific CD8-positive T cells) and remarkably differentiated and/or proliferated antigen-specific CD8-positive T cells in vivo in comparison with the extracellular vesicles of Reference Example 1 ( FIG.  5   ). In addition, it is possible that serious side effects such as cytokine storm are low because the antigen-presenting extracellular vesicles of Example 2 hardly activate other CD8-positive T cells (antigen-non-specific CD8-positive T cells) in comparison with the IL-2/anti-IL-2 antibody complex ( FIG.  5   ). 
     Test Example 4: Experiment on Activation of OVA-Specific CD4-Positive T Cells (OT-2 T Cells) In Vitro by Antigen-Presenting Extracellular Vesicles 
     The following test was conducted in vitro to determine whether the antigen-presenting extracellular vesicles activate antigen-specific CD4-positive T cells. 
     Lymph nodes extracted from an OT-2 mouse, which was an OVA-reactive CD4TCR transgenic mouse, were disrupted on a 100 μm filter to obtain a lymph node cell suspension. The cell suspension was stained using CellTrace Violet (manufactured by Thermo Fisher Scientific Inc.) as a cell proliferation assay reagent according to the manufacturer&#39;s instructions. 2×10 5  stained lymph node cells were suspended in 200 μL of an RPMI1640 medium to which 10% fetal bovine serum, 50 μNI 2-mercaptoethanol, and penicillin/streptomycin were added, the antigen-presenting extracellular vesicles of Example 3 or the extracellular vesicles of Reference Example 1 were added so that the final concentration was 10 μg/mL, and culture was performed in a 96 well round bottom plate for 4 days. After 4 days, the cells were recovered and immunostained. Antibodies used for staining are as follows (staining time: 15 minutes, temperature: 4° C.). After the staining, a luminescence intensity of CellTrace Violet as a cell proliferation assay reagent in the OT-2 T cells was detected with a flow cytometer FACSCantoII (manufactured by BD Biosciences).
         PE-Cy7-conjugated anti-mouse CD4 antibody (RM4-5, manufactured by Biolegend, Inc.)   APC-conjugated anti-mouse TCR Vb5.1, 5.2 antibody (MR9-4, manufactured by Biolegend, Inc.)       

     The results are illustrated in  FIG.  6   . 
     [Results] 
     From the results of Test Example 4, it was confirmed that the antigen-presenting extracellular vesicles of Example 3 remarkably differentiated and/or proliferated antigen-specific CD4 T cells in comparison with the extracellular vesicles of Reference Example 1 ( FIG.  6   ). 
     Test Example 5: Experiment on Differentiation Induction of OVA-Specific CD4-Positive T Cells (OT-2 T Cells) In Vitro into Regulatory T Cells by Antigen-Presenting Extracellular Vesicles 
     The following test was conducted in vitro to determine whether the antigen-presenting extracellular vesicles induce antigen-specific CD4-positive T cells into regulatory T cells (Treg). 
     Lymph nodes extracted from an OT-2 mouse, which was an OVA-reactive CD4TCR transgenic mouse, were disrupted on a 100 μm filter to obtain a lymph node cell suspension. The cell suspension was stained using CellTrace Violet (manufactured by Thermo Fisher Scientific Inc.) as a cell proliferation assay reagent according to the manufacturer&#39;s instructions. 2×10 5  stained lymph node cells were suspended in 200 μL of an RPMI1640 medium to which 10% fetal bovine serum, 50 μM 2-mercaptoethanol, and penicillin/streptomycin were added, the antigen-presenting extracellular vesicles of Example 4 or the extracellular vesicles of Reference Example 1 were added so that the final concentration was 10 μg/mL, and culture was performed in a 96 well round bottom plate for 4 days. After 4 days, the cells were recovered, and extracellular immunostaining was performed. Antibodies used for staining are as follows (staining time: 15 minutes, temperature: 4° C.). After the extracellular staining, intracellular immunostaining was performed using True-Nuclear Transcription Factor Buffer Set (manufactured by Biolegend, Inc.) and anti-mouse FOXP3 antibodies according to the manufacturer&#39;s instructions. After the intracellular staining, expression of CD25 molecules and FOXP3 molecules as markers of regulatory T cells on the OT-2 T cells was detected with a flow cytometer FACSCantoII (manufactured by BD Biosciences).
         PE-conjugated anti-mouse CD25 antibody (PC61, manufactured by Biolegend, Inc.)   PE-Cy7-conjugated anti-mouse CD4 antibody (RM4-5, manufactured by Biolegend, Inc.)   APC-conjugated anti-mouse TCR Vb5.1, 5.2 antibody (MR9-4, manufactured by Biolegend, Inc.)   Alexa Fluor 488-conjugated anti-mouse FOXP3 antibody (MF-14, manufactured by Biolegend, Inc.)       

     The results are illustrated in  FIG.  7   . 
     [Results] 
     From the results of Test Example 5, it could be seen that the antigen-presenting extracellular vesicles of Example 4 induced differentiation of the antigen-specific CD4-positive T cells into regulatory T cells (preferably, regulatory T cells expressing Foxp3) in comparison with the extracellular vesicles of Reference Example 1 ( FIG.  7   ). 
     Test Example 6: Experiment on Differentiation Induction of OVA-Specific CD4-Positive T Cells (OT-2 T Cells) In Vitro into Th2T Cells by Antigen-Presenting Extracellular Vesicles 
     The following test was conducted in vitro to determine whether antigen-presenting extracellular vesicles induce differentiation of antigen-specific CD4-positive T cells into Th2T cells. 
     Lymph nodes extracted from an OT-2 mouse, which was an OVA-reactive CD4TCR transgenic mouse, were disrupted on a 100 μm filter to obtain a lymph node cell suspension. The cell suspension was stained using CellTrace Violet (manufactured by Thermo Fisher Scientific Inc.) as a cell proliferation assay reagent according to the manufacturer&#39;s instructions. 2×10 5  stained lymph node cells were suspended in 200 μL of an RPMI1640 medium to which 10% fetal bovine serum, 50 μM 2-mercaptoethanol, and penicillin/streptomycin were added, the antigen-presenting extracellular vesicles of Example 3 or 5 or the extracellular vesicles of Reference Example 1 were added so that the final concentration was 10 μg/mL, and culture was performed in a 96 well round bottom plate for 4 days. After 4 days, the cells were recovered, and extracellular immunostaining was performed. Antibodies used for staining are as follows (staining time: 15 minutes, temperature: 4° C.). After the extracellular staining, intracellular immunostaining was performed using True-Nuclear Transcription Factor Buffer Set (manufactured by Biolegend, Inc.) and anti-GATA3 antibodies according to the manufacturer&#39;s instructions. After the intracellular staining, a luminescence intensity of CellTrace Violet as a cell proliferation assay reagent in the OT-2 T cells and expression of GATA3 as a marker of Th2T cells were detected with a flow cytometer FACSCantoII (manufactured by BD Biosciences).
         PE-conjugated anti-mouse TCR Vb5.1, 5.2 antibody (MR9-4, manufactured by Biolegend, Inc.)   PE-Cy7-conjugated anti-mouse CD4 antibody (RM4-5, manufactured by Biolegend, Inc.)   APC-conjugated anti-GATA3 antibody (16E10A23, manufactured by Biolegend, Inc.)       

     The results are illustrated in  FIG.  8   . 
     [Results] 
     From the results of Test Example 6, it could be seen that the antigen-presenting extracellular vesicles of Examples 3 and 5 induced differentiation of antigen-specific CD4-positive T cells into Th2 cells in vitro in comparison with the extracellular vesicles of Reference Example 1 ( FIG.  8   ). The Th2 cells secrete cytokines such as IL-4 or IL-5, activate differentiation of naive B cells that recognize the same antigen, and promote induction of antigen-specific IgE production (that is, activation of humoral immunity). 
     [Example 6] Antigen-Presenting Extracellular Vesicles 4 Containing MHC Class II Molecules, T-Cell Costimulatory Molecules, and T-Cell Stimulatory Cytokines in Membrane 
     HEK293T cells were seeded in a cell culture dish and cultured in a Dulbecco&#39;s modified Eagle medium to which 2% fetal bovine serum and penicillin/streptomycin were added. Cells at about 50% confluence were transfected with the four plasmids (pCAG vectors encoding sc-Dimer-CD81-IL-12p40, an MHC class IIα chain, CD80-CD9, and IL-12p35, respectively) prepared above at the same time using polyethylenimine “Max” (manufactured by Polysciences Inc.) according to the manufacturer&#39;s instructions. 3 to 12 hours after the transfection, the medium was replaced, and 24 hours after the transfection, the medium was replaced with a Dulbecco&#39;s modified Eagle medium to which 2% fetal bovine exosomes-removed serum and penicillin/streptomycin were added. 72 hours after the transfection, a supernatant was collected, and then the supernatant was centrifuged at 300 g for 5 minutes after being passed through a 0.22 μm filter. Supernatant was collected, and the supernatant was centrifuged at 2,000 g for 20 minutes. Supernatant was collected, and the supernatant was centrifuged at 10,000 g for 30 minutes. After supernatant was collected and the supernatant was centrifuged at 100,000 g for 2 hours, the supernatant was removed, and pellets were washed with PBS. After PBS was added to the pellets and the pellets were centrifuged at 100,000 g for 2 hours, supernatant was removed, and the pellets suspended in 100 μL of PBS were used as antigen-presenting extracellular vesicles of Example 6. The concentration of the antigen-presenting extracellular vesicles was measured according to the manufacturer&#39;s instructions using a BCA protein assay kit (manufactured by Thermo Fisher Scientific Inc.). 
     Test Example 1-5: Flow Cytometry Analysis of Fusion Protein Contained in Membrane of Extracellular Vesicle 
     The antigen-presenting extracellular vesicles of Example 6 were immunostained by a PS Capture (trademark) exosome flow cytometry kit (manufactured by FUJIFILM Wako Pure Chemical Corporation) according to the manufacturer&#39;s instruction. The antibodies used for the staining are as follows. After the staining, expression of each fusion protein was detected with a flow cytometer FACSCantoII (manufactured by BD Biosciences).
         Alexa Fluor 488-conjugated anti-mouse I-A/I-E antibody M5/114.15.2, manufactured by Biolegend, Inc.)   PE-conjugated anti-mouse IL-12 antibody (C15.6, manufactured by Biolegend, Inc.)   The results of APC-conjugated anti-mouse CD80 antibody (16-10A1, manufactured by Biolegend, Inc.) are illustrated in  FIG.  3 E .       

     [Results] 
     From the results of Test Example 1-5, it could be confirmed that MHC class II molecules presenting OVA antigens, CD80, and functional IL-12 were contained in the membrane of the antigen-presenting extracellular vesicle of Example 6 ( FIG.  3 E ). 
     [Example 7] Antigen-Presenting Extracellular Vesicles 5 Containing MHC Class II Molecules, T-Cell Costimulatory Molecules, and T-Cell Stimulatory Cytokines in Membrane 
     HEK293T cells were seeded in a cell culture dish and cultured in a Dulbecco&#39;s modified Eagle medium to which 2% fetal bovine serum and penicillin/streptomycin were added. Cells at about 50% confluence were transfected with the five plasmids (pCAG vectors encoding sc-Dimer-CD81, an MHC class IIα chain, CD80-CD9, CD81-IL-6, and TGF-β-MFGE8, respectively) prepared above at the same time using polyethylenimine “Max” (manufactured by Polysciences Inc.) according to the manufacturer&#39;s instructions. 3 to 12 hours after the transfection, the medium was replaced, and 24 hours after the transfection, the medium was replaced with a Dulbecco&#39;s modified Eagle medium to which 2% fetal bovine exosomes-removed serum and penicillin/streptomycin were added. 72 hours after the transfection, a supernatant was collected, and then the supernatant was centrifuged at 300 g for 5 minutes after being passed through a 0.22 μm filter. Supernatant was collected, and the supernatant was centrifuged at 2,000 g for 20 minutes. Supernatant was collected, and the supernatant was centrifuged at 10,000 g for 30 minutes. After supernatant was collected and the supernatant was centrifuged at 100,000 g for 2 hours, the supernatant was removed, and pellets were washed with PBS. After PBS was added to the pellets and the pellets were centrifuged at 100,000 g for 2 hours, supernatant was removed, and the pellets suspended in 100 μL of PBS were used as antigen-presenting extracellular vesicles of Example 7. The concentration of the antigen-presenting extracellular vesicles was measured according to the manufacturer&#39;s instructions using a BCA protein assay kit (manufactured by Thermo Fisher Scientific Inc.). 
     Test Example 1-6: Flow Cytometry Analysis of Fusion Protein Contained in Membrane of Extracellular Vesicle 
     The antigen-presenting extracellular vesicles of Example 7 were immunostained by a PS Capture (trademark) exosome flow cytometry kit (manufactured by FUJIFILM Wako Pure Chemical Corporation) according to the manufacturer&#39;s instruction. The antibodies used for the staining are as follows. After the staining, expression of each fusion protein was detected with a flow cytometer FACSCantoII (manufactured by BD Biosciences).
         FITC-conjugated anti-mouse CD80 antibody (16-10A1, manufactured by Biolegend, Inc.)   PE-conjugated anti-mouse IL-6 antibody (MP5-20F3, manufactured by Biolegend, Inc.)   APC-Cy7-conjugated anti-mouse I-A/I-E antibody (M5/114.15.2, manufactured by Biolegend, Inc.)   APC-conjugated anti-mouse LAP (TGF-α1) antibody (TW7-16B4, manufactured by Biolegend, Inc.)       

     The results are illustrated in  FIG.  3 F . 
     [Results] 
     From the results of Test Example 1-6, it could be seen that MHC class II molecules presenting OVA antigens, CD80, IL-6, and TGFb were contained in the membrane of the antigen-presenting extracellular vesicle of Example 7 ( FIG.  3 F ). 
     [Example 8] Establishment of Cell Strain Stably Expressing MHC Class I Molecules, T-Cell Costimulatory Molecules, and T-Cell Stimulatory Cytokines and Preparation of Antigen-Presenting Extracellular Vesicles 
     PLAT-A cells were seeded in a cell culture dish and cultured in a Dulbecco&#39;s modified Eagle medium to which 2% fetal bovine serum and penicillin/streptomycin were added. Cells at about 50% confluence were transfected with a pMX vector encoding CD80-CD9 or sc-Trimer-CD81-IL-2 using polyethylenimine “Max” (manufactured by Polysciences Inc.) according to manufacturer&#39;s instructions. 12 hours after the transfection, the medium was replaced, and 60 hours after the transfection, a supernatant was collected and centrifuged at 300 g for 5 minutes. The collected supernatant was used as virus particles. HEK293 cells were seeded in a cell culture dish and cultured in a Dulbecco&#39;s modified Eagle medium to which 2% fetal bovine serum and penicillin/streptomycin were added. A DOTAP transfection reagent (Roche) was added to viral particles in which the CD80-CD9 adjusted above was incorporated into the cells at about 50% confluence according to the manufacturer&#39;s instructions, and the mixture was added to HEK293 cells. The cells to which the viral particles were added were centrifuged at 2,500 rpm for 3 minutes. 24 hours after the transfection, the medium was replaced, and 1 week after the transfection, CD80-positive cells were sorted with FACSMelody (manufactured by BD Biosciences). The sorted CD80-positive cells were cultured for 1 week, and the cultured cells were seeded in a dish and cultured in a Dulbecco&#39;s modified Eagle medium to which 2% fetal bovine serum and penicillin/streptomycin were added. A DOTAP transfection reagent was added to viral particles in which the sc-Trimer-CD81-IL-2 prepared above was incorporated into the cells at about 50% confluence according to the manufacturer&#39;s instructions, and the mixture was added to CD80-positive HEK293 cells. The cells to which the viral particles were added were centrifuged at 2,500 rpm for 3 minutes. 24 hours after the transfection, the medium was replaced, and 1 week after the transfection, CD80-positive and MHCI-positive cells were sorted with FACSMelody (manufactured by BD Biosciences). The sorted cells were used as stable expression cells. The stable expression cells were seeded in a dish and cultured in a Dulbecco&#39;s modified Eagle medium to which 2% fetal bovine serum and penicillin/streptomycin were added. The supernatant of the cells at about 50% confluence was replaced with a Dulbecco&#39;s modified Eagle medium to which 2% fetal bovine exosomes-removed and penicillin/streptomycin were added. 72 hours after the medium replacement, supernatant was collected, and then the supernatant was centrifuged at 300 g for 5 minutes after being passed through a 0.22 μm filter. Supernatant was collected, and the supernatant was centrifuged at 2,000 g for 20 minutes. Supernatant was collected, and the supernatant was centrifuged at 10,000 g for 30 minutes. After supernatant was collected and the supernatant was centrifuged at 100,000 g for 2 hours, the supernatant was removed, and pellets were washed with PBS. After PBS was added to the pellets and the pellets were centrifuged at 100,000 g for 2 hours, supernatant was removed, and the pellets suspended in 100 μL of PBS were used as antigen-presenting extracellular vesicles of Example 8. 
     Test Example 1-7: Flow Cytometry Analysis of Fusion Protein Contained in Membrane of Extracellular Vesicle 
     The antigen-presenting extracellular vesicles of Example 8 were immunostained by a PS Capture (trademark) exosome flow cytometry kit (manufactured by FUJIFILM Wako Pure Chemical Corporation) according to the manufacturer&#39;s instruction. Antibodies used for staining are as follows (staining time: 15 minutes, temperature: 4° C.). After the staining, expression of each fusion protein was detected with a flow cytometer FACSCantoII (manufactured by BD Biosciences).
         PE-conjugated anti-mouse H-2KbOVA complex antibody (25-D1.16, manufactured by Biolegend, Inc.)   FITC-conjugated anti-mouse CD80 antibody (16-10A1, manufactured by Biolegend, Inc.)   APC-conjugated anti-mouse IL-2 antibody (JES6-5H4, manufactured by Biolegend, Inc.)       

     The results are illustrated in  FIG.  3 G . 
     [Results] 
     From the results of Test Example 1-7, it could be confirmed that MHC class I molecules presenting OVA antigens, CD80, and IL-2 were contained in the membrane of the antigen-presenting extracellular vesicle of Example 8 ( FIG.  3 G ). 
     [Example 9] Antigen-Presenting Extracellular Vesicles Containing HLA Class I Molecules, Human T-Cell Costimulatory Molecules, and Human T-Cell Stimulatory Cytokines in Membrane 
     HEK293T cells in which B2m was deleted were seeded in a cell culture dish and cultured in a Dulbecco&#39;s modified Eagle medium to which 2% fetal bovine serum and penicillin/streptomycin were added. Cells at about 50% confluence were transfected with the two plasmids (pCAG vectors encoding HLAsc-Trimer-human CD81, human CD80-human CD9, and CD63-IL2, respectively) prepared above at the same time using polyethylenimine “Max” (manufactured by Polysciences Inc.) according to the manufacturer&#39;s instructions. 3 to 12 hours after the transfection, the medium was replaced, and 24 hours after the transfection, the medium was replaced with a Dulbecco&#39;s modified Eagle medium to which 2% fetal bovine exosomes-removed serum and penicillin/streptomycin were added. 72 hours after the transfection, supernatant was collected, and then the supernatant was centrifuged at 300 g for 5 minutes after being passed through a 0.22 μm filter. Supernatant was collected, and the supernatant was centrifuged at 2,000 g for 20 minutes. Supernatant was collected, and the supernatant was centrifuged at 10,000 g for 30 minutes. After supernatant was collected and the supernatant was centrifuged at 100,000 g for 2 hours, the supernatant was removed, and pellets were washed with PBS. After PBS was added to the pellets and the pellets were centrifuged at 100,000 g for 2 hours, supernatant was removed, and the pellets suspended in 100 μL of PBS were used as human antigen-presenting extracellular vesicles of Example 9. The concentration of the antigen-presenting extracellular vesicles was measured according to the manufacturer&#39;s instructions using a BCA protein assay kit (manufactured by Thermo Fisher Scientific Inc.). 
     By using SARS-CoV2sc-Trimer-hCD81 instead of hsc-Trimer-hCD81, it is possible to prepare human antigen-presenting extracellular vesicles presenting antigen-presenting MHC molecules presenting SARS-CoV2 peptides as antigens, hCD80, and hIL-2 on a surface thereof. 
     Test Example 1-8: Flow Cytometry Analysis of Fusion Protein Contained in Membrane of Extracellular Vesicle 
     The antigen-presenting extracellular vesicles of Example 9 were immunostained by a PS Capture (trademark) exosome flow cytometry kit (manufactured by FUJIFILM Wako Pure Chemical Corporation) according to the manufacturer&#39;s instruction. Antibodies used for staining are as follows (staining time: 15 minutes, temperature: 4° C.). After the staining, expression of each fusion protein was detected with a flow cytometer FACSCantoII (manufactured by BD Biosciences).
         APC-conjugated anti-human IL-2 antibody (MQ1-17H12, manufactured by Biolegend, Inc.)   PE-conjugated anti-human CD80 antibody (2D10, manufactured by Biolegend, Inc.)   APC-conjugated anti-human β2m antibody (2M2, manufactured by Biolegend, Inc.)       

     The results are illustrated in  FIG.  3 H . 
     [Results] 
     From the results of Test Example 1-8, it could be confirmed that MHC class I molecules presenting WT1 antigens, hCD80, and hIL-2 were contained in the membrane of the antigen-presenting extracellular vesicle of Example 9 ( FIG.  3 H ). 
     Test Example 7: Experiment on Differentiation Induction of OVA-Specific CD4-Positive T Cells (OT-2 T Cells) In Vitro into Th1T Cells by Antigen-Presenting Extracellular Vesicles 
     The following test was conducted in vitro to determine whether the antigen-presenting extracellular vesicles induce differentiation of antigen-specific CD4-positive T cells into Th1T cells. 
     Lymph nodes extracted from an OT-2 mouse, which was an OVA-reactive CD4TCR transgenic mouse, were disrupted on a 100 μm filter to obtain a lymph node cell suspension. The cell suspension was stained using CellTrace Violet (manufactured by Thermo Fisher Scientific Inc.) as a cell proliferation assay reagent according to the manufacturer&#39;s instructions. 2×10 5  stained lymph node cells were suspended in 200 μL of an RPMI1640 medium to which 10% fetal bovine serum, 50 μM 2-mercaptoethanol, and penicillin/streptomycin were added, the antigen-presenting extracellular vesicles of Example 3 or 6 or the extracellular vesicles of Reference Example 1 were added so that the final concentration was 10 μg/mL, and culture was performed in a 96 well round bottom plate for 4 days. After 4 days, the cells were recovered, and extracellular immunostaining was performed. Antibodies used for staining are as follows (staining time: 15 minutes, temperature: 4° C.). After the extracellular staining, intracellular immunostaining was performed using True-Nuclear Transcription Factor Buffer Set (manufactured by Biolegend, Inc.) and anti-T-bet antibodies according to the manufacturer&#39;s instructions. After the intracellular staining, a luminescence intensity of CellTrace Violet as a cell proliferation assay reagent in the OT-2 T cells and expression of T-bet as a marker of Th1T cells were detected with a flow cytometer FACSCantoII (manufactured by BD Biosciences).
         PerCP/Cy5.5-conjugated anti-mouse TCRVa2 antibody (B20.1, manufactured by Biolegend, Inc.)   APC-Cy7-conjugated anti-mouse CD4 antibody (RM4-5, manufactured by Biolegend, Inc.)   PE-conjugated anti-T-bet antibody (4B10, manufactured by Biolegend, Inc.)       

     The results are illustrated in  FIG.  9   . 
     [Results] 
     From the results of Test Example 7, it was confirmed that the antigen-presenting extracellular vesicles of Example 6 induced differentiation of antigen-specific CD4-positive T cells into Th1 cells in vitro in comparison with the extracellular vesicles of Reference Example 1 ( FIG.  9   ). The Th1 cells produce IFN-γ, IL-2, or the like, and promote activation of macrophages and cytotoxic T cells that destroy pathogen cells, virus-infected cells, cancer cells, and the like (that is, activation of cellular immunity). 
     Test Example 8: Experiment on Differentiation Induction of OVA-Specific CD4-Positive T Cells (OT-2 T Cells) In Vitro into Th17T Cells by Antigen-Presenting Extracellular Vesicles 
     The following test was conducted in vitro to determine whether the antigen-presenting extracellular vesicles induce differentiation of antigen-specific CD4-positive T cells into Th17T cells. 
     Lymph nodes extracted from a mouse obtained by mating an OVA-reactive CD4TCR transgenic mouse and an RORrt-GFP mouse were disrupted on a 100 μm filter to obtain a lymph node cell suspension. The cell suspension was stained using CellTrace Violet (manufactured by Thermo Fisher Scientific Inc.) as a cell proliferation assay reagent according to the manufacturer&#39;s instructions. 2×10 5  stained lymph node cells were suspended in 200 μL of an RPMI1640 medium to which 10% fetal bovine serum, 50 μM 2-mercaptoethanol, and penicillin/streptomycin were added, the antigen-presenting vesicles of Example 7 or the extracellular vesicles of Reference Example 1 were added so that the final concentration was 10 μg/mL, and culture was performed in a 96 well round bottom plate for 4 days. After 4 days, the cells were recovered, and extracellular immunostaining was performed. Antibodies used for staining are as follows (staining time: 15 minutes, temperature: 4° C.). After the intracellular staining, a luminescence intensity of CellTrace Violet as a cell proliferation assay reagent in the OT-2 T cells and expression of RORrt as a marker of Th17T cells were detected with a flow cytometer FACSCantoII (manufactured by BD Biosciences).
         APC-conjugated anti-mouse TCRVa2 antibody (B20.1, manufactured by Biolegend, Inc.)   PE-Cy7-conjugated anti-mouse CD4 antibody (RM4-5, manufactured by Biolegend, Inc.)   PE-conjugated anti-mouse TCR Vb5.1, 5.2 antibody (MR9-4, manufactured by Biolegend, Inc.)       

     The results are illustrated in  FIG.  10   . 
     [Results] 
     From the results of Test Example 8, it could be seen that the antigen-presenting extracellular vesicles of Example 7 induced differentiation of antigen-specific CD4-positive T cells into Th17 cells in vitro in comparison with the extracellular vesicles of Reference Example 1 ( FIG.  10   ). Unlike the Th1 or Th2 cells, the Th17 cells produce inflammatory cytokines such as IL-17, IL-21, IL-22, and TNF-α to induce inflammation, promote recruitment and proliferation of neutrophils and monocytes, and contribute to infection defense of fungi (including pathogenic fungi such as  candida, Staphylococcus aureus , and  Streptococcus pyogenes ). 
     Test Example 9: Experiment on Activation of OVA-Specific CD8-Positive T Cells (OT-1 T Cells) In Vitro by Antigen-Presenting Extracellular Vesicles Obtained by Purification of Stable Cell Strain 
     The following test was conducted in vitro to determine whether the antigen-presenting extracellular vesicles obtained by purification of a stable cell line activate antigen-specific CD8-positive T cells. 
     Lymph nodes extracted from an OT-1 mouse, which was an OVA-reactive TCR transgenic mouse, were disrupted on a 100 μm filter to obtain a lymph node cell suspension. The cell suspension was stained using CellTrace Violet (manufactured by Thermo Fisher Scientific Inc.) as a cell proliferation assay reagent according to the manufacturer&#39;s instructions. 2×10 5  stained lymph node cells were suspended in 200 μL of an RPMI1640 medium to which 10% fetal bovine serum, 50 μM 2-mercaptoethanol, and penicillin/streptomycin were added, the antigen-presenting extracellular vesicles of Example 1 or 8 or the extracellular vesicles of Reference Example 1 were added so that the final concentration was 9 μg/mL, and culture was performed in a 96 well round bottom plate for 4 days. After the culture in the 96 well round bottom plate for 3 days, immunostaining was performed. Antibodies used for staining are as follows (staining time: 15 minutes, temperature: 4° C.). After the staining, a luminescence intensity of CellTrace Violet as a cell proliferation assay reagent in the OT-1 T cells was detected with a flow cytometer FACSCantoII (manufactured by BD Biosciences).
         APC-conjugated anti-mouse CD8 antibody (53-6.7, manufactured by Biolegend, Inc.)   PE-conjugated anti-mouse TCR Vb5.1, 5.2 antibody (MR9-4, manufactured by Biolegend, Inc.)       

     The results are illustrated in  FIG.  11   . 
     [Results] 
     From the results of Test Example 9, it was confirmed that the antigen-presenting extracellular vesicles of Examples 1 and 8 remarkably proliferated antigen-specific CD8-positive T cells in comparison with the extracellular vesicles of Reference Example 1 ( FIG.  11   ). This indicates that not only the extracellular vesicles in which the constitutional requirement (A) exemplified by sc-Trimer-CD81 and the constitutional requirement (B) exemplified by CD81-IL-2 are present as different proteins, but also the extracellular vesicles in which a fusion protein having both functions, which is exemplified by sc-Trimer-CD81-IL-2, is present, exhibit equivalent effects on T cells. 
     Test Example 10: Experiment for Evaluating Anti-Tumor Effect by Antigen-Presenting Extracellular Vesicles 
     In order to determine whether the antigen-presenting extracellular vesicles obtained by purification of a stable cell strain have an anti-tumor effect, 1×10 5  B16 melanoma cells expressing OVA were subcutaneously ingested in a CD45.1/CD45.2 congenic mouse, and 1×10 5  OT-1T cells were transferred after 3 days. After 1 day, 4 days, and 7 days after the OT-1T cell transfer, 50 μg of the antigen-presenting extracellular vesicles of Example 8 or the extracellular vesicles of Reference Example 1 were transferred from the tail vein of the recipient mouse, and the size of the B16 melanoma cells was observed. 
     [Results] 
     From the results of Test Example 10, it was confirmed that the antigen-presenting extracellular vesicles of Example 8 remarkably suppressed proliferation of B16 melanoma cells in comparison with the extracellular vesicles of Reference Example 1 ( FIG.  12   ). This indicates that not only the extracellular vesicles in which the constitutional requirement (A) exemplified by sc-Trimer-CD81 and the constitutional requirement (B) exemplified by CD81-IL-2 are present as different proteins, but also the extracellular vesicles in which a fusion protein having both functions, which is exemplified by sc-Trimer-CD81-IL-2, is present, exhibit equivalent medicinal effects. 
     [Example 10] Antigen-Presenting Extracellular Vesicles Containing sc-Trimer-CD81-IL-2 Fusion Protein in Membrane 
     HEK293T cells were seeded in a cell culture dish and cultured in a Dulbecco&#39;s modified Eagle medium to which 2% fetal bovine serum and penicillin/streptomycin were added. Cells at about 50% confluence were transfected with the plasmid (an expression vector expressing sc-Trimer-CD81-IL-2) prepared above using polyethylenimine “Max” (manufactured by Polysciences Inc.) according to manufacturer&#39;s instructions. Antigen-presenting extracellular vesicles were prepared from the cells after the transfection by the method described above. 
     Reference Example 6: Antigen-Presenting Extracellular Vesicles Containing CD63-AkaLuc Fusion Protein in Membrane 
     HEK293T cells were seeded in a cell culture dish and cultured in a Dulbecco&#39;s modified Eagle medium to which 2% fetal bovine serum and penicillin/streptomycin were added. Cells at about 50% confluence were transfected with the plasmid (an expression vector expressing CD63-AkaLuc) prepared above using polyethylenimine “Max” (manufactured by Polysciences Inc.) according to manufacturer&#39;s instructions. Antigen-presenting extracellular vesicles were prepared from the cells after the transfection by the method described above. 
     Test Example 11: Experiment on Activation of OVA-Specific CD8-Positive T Cells (OT-1 T Cells) In Vivo by Antigen-Presenting Extracellular Vesicles Containing sc-Trimer-CD81-IL-2 Fusion Protein in Membrane 
     Lymph nodes extracted from an OT-1 mouse, which was an OVA-reactive TCR transgenic mouse, were disrupted on a 100 μm filter to obtain a lymph node cell suspension. Lymph nodes were similarly extracted from a CD45.1 congenic mouse, and a lymphocyte suspension was prepared. The respective lymphocyte suspensions were mixed at a ratio of 1:1, and the mixture was stained using CellTrace Violet as a cell proliferation assay reagent. 1×10 7  CellTrace Violet-stained mixed lymphocyte suspension suspended in PBS was transferred from the tail vein of the CD45.1/CD45.2 congenic mouse. The next day, 50 μg of the extracellular vesicles of Example 11 or Reference Example 6 were transferred from the tail vein to a CD45.1/CD45.2 congenic mouse. 4 days after cell transfer, the spleen was extracted from the recipient mouse, and a lymphocyte suspension was prepared and immunostained. The following antibodies were used for the staining (staining time: 15 minutes, temperature: 4° C.). After the staining, a luminescence intensity of CellTrace Violet as a cell proliferation assay reagent in the transferred OT-1 T cells and wild-type CD8T cells was detected with a flow cytometer FACSCantoII (manufactured by BD Biosciences).
         PE-Cy7-conjugated anti-mouse CD8 antibody (53-6.7, manufactured by Biolegend, Inc.)   PE-conjugated anti-mouse TCR Vb5.1, 5.2 antibody (MR9-4, manufactured by Biolegend, Inc.)   FITC-conjugated anti-mouse CD45.1 antibody (A20, manufactured by Biolegend, Inc.)   APC-conjugated anti-mouse CD45.2 antibody (104, manufactured by Biolegend, Inc.)       

     The extracellular vesicles of Example 10 hardly activate other CD8-positive T cells (antigen-non-specific CD8-positive T cells) and can remarkably differentiate and/or proliferate antigen-specific CD8-positive T cells in vivo in comparison with the extracellular vesicles of Reference Example 6. 
     Test Example 12: Experiment on Activation of Intrinsic OVA-Reactive T Cells by Extracellular Vesicles Expressing sc-Trimer-CD81-IL-2 Fusion Protein 
     50 μg of the extracellular vesicles of Example 10 or Reference Example 6 were transferred from a tail vein of a C57BL/6 mouse. 4 days after transfer, the spleen was extracted from the recipient mouse, a lymphocyte suspension was prepared, and OVA-reactive T cells were immunostained with a tetramer according to the manufacturer&#39;s instructions. The following antibodies were used for the staining. After the staining, tetramer-positive cells were detected with a flow cytometer FACSCantoII (manufactured by BD Biosciences).
         APC-conjugated H-2Kb OVA Tetramer (Tetramer Shop ApS)   PE-conjugated H-2Kb OVA Tetramer (Tetramer Shop ApS)   Brilliant Violet421-conjugated anti-mouse CD8 antibody (53-6.7, manufactured by Biolegend, Inc.)       

     The extracellular vesicles of Example 10 can proliferate OVA-reactive CD8T cells that are remarkably intrinsically present, in comparison with the extracellular vesicles of Reference Example 6. 
     Hereinabove, as described in the examples, the antigen-presenting extracellular vesicles and polynucleotides described in the present specification can satisfactorily activate, proliferate, and/or differentiate antigen-specific T cells (for example, antigen-specific CD8-positive T cells, antigen-specific CD4-positive cells, and the like). 
     Hereinafter, a summary of the sequences included in the sequence listing will be described. 
     
       
         
           
               
               
             
               
                 TABLE 15 
               
             
            
               
                   
               
               
                   
                 SEQ ID NO: 
               
            
           
           
               
               
               
            
               
                   
                 Amino acid 
                   
               
               
                   
                 sequence 
                 Polynucleotide 
               
               
                   
               
               
                 Signal peptide of β 2   
                   1 
                   2 
               
               
                 microglobulin 
                   
                   
               
               
                 β 2  Microglobulin 
                   7 
                   8 
               
               
                 (from which signal peptide 
                   
                   
               
               
                 is removed) 
                   
                   
               
               
                 MHC class Iα chain 
                   9 
                 1 0 
               
               
                 (from which signal peptide 
                   
                   
               
               
                 is removed) 
                   
                   
               
               
                 Signal peptide of MHC 
                 3 3 
                 3 4 
               
               
                 class IIβ chain 
                   
                   
               
               
                 MHC class IIβ chain 
                 3 7 
                 3 8 
               
               
                 (from which signal peptide 
                   
                   
               
               
                 is removed) 
                   
                   
               
               
                 MHC class IIα chain 
                 4 5 
                 4 6 
               
               
                 (full length) 
                   
                   
               
               
                 MHC class IIα chain 
                 7 1 
                 7 2 
               
               
                 (from which signal peptide 
                   
                   
               
               
                 is removed) 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
             
               
                 TABLE 16 
               
             
            
               
                   
               
               
                   
                 SEQ ID NO: 
               
            
           
           
               
               
               
            
               
                   
                 Amino acid 
                   
               
               
                   
                 sequence 
                 Polynucleotide 
               
               
                   
               
               
                 OVA PEPTIDE 1 
                   3 
                   4 
               
               
                 (for MHC class I molecule) 
                   
                   
               
               
                 OVA PEPTIDE 2 
                 3 5 
                 3 6 
               
               
                 (for MHC class II 
                   
                   
               
               
                 molecule) 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
             
               
                 TABLE 17 
               
             
            
               
                   
               
               
                   
                 SEQ ID NO: 
               
            
           
           
               
               
               
            
               
                   
                 Amino acid 
                   
               
               
                   
                 sequence 
                 Polynucleotide 
               
               
                   
               
               
                 CD9 (full length) 
                 2 1 
                 2 2 
               
               
                 CD63 (full length) 
                 2 7 
                 2 8 
               
               
                 CD63 
                 5 7 
                 5 8 
               
               
                 (partial sequence containing 
                   
                   
               
               
                 TM1 to TM3) 
                   
                   
               
               
                 CD63 
                 5 9 
                 6 0 
               
               
                 (partial sequence containing 
                   
                   
               
               
                 TM4) 
                   
                   
               
               
                 CD81 (full length) 
                 1 5 
                 1 6 
               
               
                 CD81 
                 6 1 
                 6 2 
               
               
                 (partial sequence containing 
                   
                   
               
               
                 TM1 to TM3) 
                   
                   
               
               
                 CD81 
                 6 3 
                 6 4 
               
               
                 (partial sequence containing 
                   
                   
               
               
                 TM4) 
                   
                   
               
               
                 MFG-E8 
                 4 9 
                 5 0 
               
               
                 (from which signal peptide is 
                   
                   
               
               
                 removed) 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
             
               
                 TABLE 18 
               
             
            
               
                   
               
               
                   
                 SEQ ID NO: 
               
            
           
           
               
               
               
            
               
                   
                 Amino acid 
                   
               
               
                   
                 sequence 
                 Polynucleotide 
               
               
                   
               
               
                 IL-2 
                 2 5 
                 2 6 
               
               
                 (from which signal peptide 
                   
                   
               
               
                 is removed) 
                   
                   
               
               
                 IL-4 
                 5 3 
                 5 4 
               
               
                 (from which signal peptide 
                   
                   
               
               
                 is removed) 
                   
                   
               
               
                 TGF-β1 (full length) 
                 4 7 
                 4 8 
               
               
                 TGF-β1 
                 7 3 
                 7 4 
               
               
                 (from which signal peptide 
                   
                   
               
               
                 is removed) 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
             
               
                 TABLE 19 
               
             
            
               
                   
               
               
                   
                 SEQ ID NO: 
               
            
           
           
               
               
               
            
               
                   
                 Amino acid 
                   
               
               
                   
                 sequence 
                 Polynucleotide 
               
               
                   
               
               
                 CD80 (full length) 
                 1 9 
                 2 0 
               
               
                 CD80 
                 6 7 
                 6 8 
               
               
                 (from which signal peptide 
                   
                   
               
               
                 is removed) 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
             
               
                 TABLE 20 
               
             
            
               
                   
               
               
                   
                 SEQ ID NO: 
               
            
           
           
               
               
               
            
               
                   
                 Amino acid 
                   
               
               
                   
                 sequence 
                 Polynucleotide 
               
               
                   
               
               
                 Peptide linker 1 
                   5 
                   6 
               
               
                 Peptide linker 2 
                 1 1 
                 1 2 
               
               
                 Peptide linker 3 
                 2 9 
                 3 0 
               
               
                 Peptide linker 4 
                 3 9 
                 4 0 
               
               
                 Peptide linker 5 
                 7 7 
                 7 8 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
             
               
                 TABLE 21 
               
             
            
               
                   
               
               
                   
                 SEQ ID NO: 
               
            
           
           
               
               
               
            
               
                   
                 Amino acid 
                   
               
               
                   
                 sequence 
                 Polynucleotide 
               
               
                   
               
               
                 Single chain MHC class 
                 6 5 
                 6 6 
               
               
                 I molecule 
                   
                   
               
               
                 (β  2  microglobulin + 
                   
                   
               
               
                 MHC class Iα chain) 
                   
                   
               
               
                 sc-Trimer 
                 1 3 
                 1 4 
               
               
                 (OVA peptide 1 + 
                   
                   
               
               
                 single chain MHC class 
                   
                   
               
               
                 I molecule) 
                   
                   
               
               
                 sc-Trimer +  
                 1 7 
                 1 8 
               
               
                 CD81 (full length) 
                   
                   
               
               
                 sc-Dimer 
                 4 1 
                 4 2 
               
               
                 (OVA peptide 2 + 
                   
                   
               
               
                 MHC class IIβ chain) 
                   
                   
               
               
                 sc-Dimer +  
                 4 3 
                 4 4 
               
               
                 CD81 (full length) 
                   
                   
               
               
                 CD63-IL-2 
                 3 1 
                 3 2 
               
               
                 CD81-IL-4 
                 5 5 
                 5 6 
               
               
                 TGF-β1 (full length) + 
                 5 1 
                 5 2 
               
               
                 MGF-E8 (from which 
                   
                   
               
               
                 signal peptide is removed) 
                   
                   
               
               
                 TGF-B1 (from which 
                 7 5 
                 7 6 
               
               
                 signal peptide is removed) + 
                   
                   
               
               
                 MGF-E8 (from which 
                   
                   
               
               
                 signal peptide is removed) 
                   
                   
               
               
                 CD80 (full length) + 
                 2 3 
                 2 4 
               
               
                 CD9 (full length) 
                   
                   
               
               
                 CD80 (from which signal 
                 6 9 
                 7 0 
               
               
                 peptide is removed) + 
                   
                   
               
               
                 CD9 (full length) 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
             
               
                 TABLE 22 
               
             
            
               
                   
               
               
                   
                 SEQ ID NO: 
               
            
           
           
               
               
               
            
               
                   
                 Amino acid 
                   
               
               
                   
                 sequence 
                 Polynucleotide 
               
               
                   
               
               
                 PNE tag 
                 7 9 
                 8 0 
               
               
                 Anti-PNE tag nanobody 
                 8 1 
                 8 2 
               
               
                 (full length) 
                   
                   
               
               
                 Anti-PNE tag nanobody 
                 8 3 
                 8 4 
               
               
                 (from which signal peptide 
                   
                   
               
               
                 is removed) 
                   
                   
               
               
                 CD8a 
                 8 5 
                 8 6 
               
               
                 Anti-PNE tag nanobody 
                 8 7 
                 8 8 
               
               
                 (full length) + CD8a + 
                   
                   
               
               
                 CD81 (full length) 
                   
                   
               
               
                 Anti-PNE tag nanobody 
                 8 9 
                 9 0 
               
               
                 (from which signal peptide 
                   
                   
               
               
                 is removed) + CD8a +  
                   
                   
               
               
                 CD81 (full length) 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
               
             
               
                 TABLE 23-1 
               
             
            
               
                   
               
               
                   
                 SEQ ID NO: 
               
            
           
           
               
               
               
            
               
                   
                 Amino acid 
                   
               
               
                   
                 sequence 
                 Polynucleotide 
               
               
                   
               
            
           
           
               
               
               
            
               
                 sc-Dimer-CD81-IL-12α 
                 91 
                 92 
               
               
                 IL-12α 
                 93 
                 94 
               
               
                 (from which signal peptide is removed) 
                   
                   
               
               
                 CD81-IL-12a 
                 95 
                 96 
               
               
                 IL-12β 
                 97 
                 98 
               
               
                 IL-6 
                 99 
                 100 
               
               
                 (from which signal peptide is removed) 
                   
                   
               
               
                 CD81-IL-6 
                 101 
                 102 
               
               
                 hCD80 
                 103 
                 104 
               
               
                 hCD9 
                 105 
                 106 
               
               
                 hCD80-hCD9 
                 107 
                 108 
               
               
                 hIL-2 
                 109 
                 110 
               
               
                 (from which signal peptide is removed) 
                   
                   
               
               
                 hCD63 
                 111 
                 112 
               
               
                 (amino acids 1 to 170) 
                   
                   
               
               
                 hCD63 
                 113 
                 114 
               
               
                 (amino acids 171 to 238) 
                   
                   
               
               
                 hCD63-IL-2 
                 115 
                 116 
               
               
                 Signal peptide of hβ2 microglobulin 
                 117 
                 118 
               
               
                 WT1 PEPTIDE 1 
                 119 
                 120 
               
               
                 (for MHC class I molecule) 
                   
                   
               
               
                 h32 Microglobulin 
                 121 
                 122 
               
               
                 (from which signal peptide is removed) 
                   
                   
               
               
                 hMHC class Iα chain 
                 123 
                 124 
               
               
                 (from which signal peptide is removed) 
                   
                   
               
               
                 h single chain MHC class I molecule 
                 125 
                 126 
               
               
                 (β2 microglobulin (from which signal peptide 
                   
                   
               
               
                 is removed) + peptide linker 2 + MHC class 
                   
                   
               
               
                 Iα chain (from which signal peptide is 
                   
                   
               
               
                 removed)) 
                   
                   
               
               
                 hsc-Trimer 
                 127 
                 128 
               
               
                 (WT1 peptide 1 + peptide linker 1 + single 
                   
                   
               
               
                 chain MHC class I molecule) 
                   
                   
               
               
                 hCD81 
                 129 
                 130 
               
               
                 hsc-Trimer-CD81 
                 131 
                 132 
               
               
                 (sc-Trimer + CD81) 
                   
                   
               
               
                 CD81-IL-2 
                 133 
                 134 
               
               
                 sc-Trimer-CD81-IL-2 
                 135 
                 136 
               
               
                 (sc-Trimer + CD8) 
                   
                   
               
               
                 Aka-Luc 
                 137 
                 138 
               
               
                 CD63-Aka-Luc 
                 139 
                 140 
               
               
                 SARS-CoV2 peptide 1 
                 141 
                 142 
               
               
                 hMHC class I (HLA-A0201) α chain 
                 143 
                 144 
               
               
                 (from which signal peptide is removed) 
                   
                   
               
               
                 h single chain MHC class I molecule 
                 145 
                 146 
               
               
                 (β2 microglobulin (from which signal peptide 
                   
                   
               
               
                 is removed) + peptide linker 2 + MHC class 
                   
                   
               
               
                 I (HLA-A0201) α chain (from which signal 
                   
                   
               
               
                 peptide is removed)) 
                   
                   
               
               
                 hsc-Trimer 
                 147 
                 148 
               
               
                 (SARS-CoV2 peptide 1 + peptide linker 1 + 
                   
                   
               
               
                 single chain MHC class I (HLA-A0201) 
                   
                   
               
               
                 molecule) 
                   
                   
               
               
                 hsc-Trimer-CD81 
                 149 
                 150 
               
               
                 (SARS-CoV2sc-Trimer + CD81)