CD antigens 2001 (2001)

The process of categorizing the antigenic molecules and epitopes associated with human white cells, via the collaborative study of monoclonal antibodies, dates back to the early 1980s, when the first HLDA (Human Leukocyte Differentiation Antigen) Workshop was held in Paris. This initial meeting listed only 15 agreed molecular entities, but it created an internationally agreed basis for the nomenclature of leukocyte molecules (the CD scheme), and also provided a forum for reporting studies on their function and practical relevance. A further six HLDA meetings have been held since the first Paris meeting. The most recent of these ("HLDA7") took place last year in Harrogate, GB, and the proceedings of the meeting will be published later this year (Leucocyte Typing VII, Oxford University Press). The limitations of "blind" antibody screening: It was apparent at the previous meeting, HLDA6, held in Kobe, Japan in 1996, that the technique of detecting molecular entities by screening coded panels of monoclonal antibodies against human cells was becoming obsolescent. Antibodies to the most immunogenic molecules had already been produced, and fewer laboratories than in the early days were prepared to devote resources to raising new antibodies, since the probability of finding novel reagents becomes ever less likely. In consequence many antibodies in the 6th Workshop were reagents (submitted by laboratories that were not equipped to characterize them) which proved to be of known specificity. Selection of antibodies: With these considerations in mind the 7th Workshop adopted a different approach: instead of screening poorly characterised antibodies, reagents were selected (and actively solicited) for which at least some molecular data were already available. A substantial number of monoclonal antibodies reactive with leukocyte-associated molecules exist that do not meet the traditional criterion for establishing a new CD specificity (i. e., the existence of at least two independent antibodies of the same specificity). This rule dates from the first HLDA Workshop two decades ago: since that time biochemical and molecular biological techniques for characterizing the targets of new antibodies have come to be widely used. In consequence it is now considered appropriate to establish a CD designation for a molecule if its gene has been cloned and at least one specific monoclonal antibody has been studied in the Workshop. New Workshop Sections: Four new Sections were introduced in the 7th HLDA Workshop to add to the traditional list from past meetings: namely Dendritic Cells, Stem / progenitor Cells, Erythroid Cells and Carbohydrate Structures. Although it has been recognized for many years that monoclonal antibodies reactive with human leukocytes can be specific for carbohydrate epitopes (e. g. the carbohydrate CD category CD15 was identified at the first Workshop), they had not received specific attention in any Workshop. The inclusion of erythroid molecules, although it may seem out of place in a "Leukocyte Workshop", was justified by the number of molecules shared between white and red cells (e. g. cytokine receptors) that hint at unexplored functions of red cells. This more active approach to the identification of new CD specificities represented a break with tradition, but the results justified the new approach, since a total of well over 80 new entities were added to the list of CD specificities. This compares favourably with previous Workshops (an average of less than 30 CD specificities per Workshop), and it also largely avoided the laborious screening in multiple laboratories of antibodies that prove to be directed against known CD molecules. Tables 1 and 2 list the new specificities established at the 7th Workshop. Full details will be found in Leukocyte Typing VII, and molecular, functional and other data can be found for many of these new specificities on the PROW (Protein Reviews on the Web) Web site (http://www.ncbi.nlm.nih.gov / prov / ). CD designation Name Section Locus link CD15u Sulfated CD15 Carbohydrate structures CD60a GD3 Carbohydrate structures CD60b 9-O-acetyl-GD3 Carbohydrate structures CD60c 7-O-acetyl-GD3 Carbohydrate structures CD75 Lactosamines Carbohydrate structures CD75s Alpha-2,6-sialylated lactosamines (formerly CDw75 and CDw76) Carbohydrate structures CD85 ILT / LIR family (see Table 2 Dendritic cells CD110 MPL, TPO R Platelets 4352 CD111 PRR1 / Nectin1 Myeloid cells 5818 CD112 PRR2 Myeloid cells 5819 CD133 AC133 Stem / progenitor cells 8842 CD156b TACE / ADAM17 Adhesion structures 6868 CD158 KIR family (see Table 2) NK cells CD159a NKG2A NK cells 3821 CD160 BY55 T cells 11126 CD162R PEN5 NK cells 6404 CD167a Discoidin domain R (DDR1) Adhesion structures 780 CD168 RHAMM Adhesion structures 3161 CD169 Sialoadhesin Adhesion structures 6614 CD170 Siglec-5 Adhesion structures 8778 CD171 L1 Adhesion structures 3897 CD172a SIRP alpha Adhesion structures 8194 CD173 Blood group H type 2 Carbohydrate structures CD174 Lewis y Carbohydrate structures CD175 Tn Carbohydrate structures CD175s Sialyl-Tn Carbohydrate structures CD176 TF Carbohydrate structures CD177 NB1 Myeloid cells CD178 Fas ligand Cytokine / chemokine receptors 356 CD179a Vpre-B B cells 7441 CD179b Lambda 5 B cells 3543 CD180 RP105 B cells 4064 CD183 CXCR3 Cytokine / chemokine receptors 2833 CD184 CXCR4 Cytokine / chemokine receptors 7852 CD195 CCR5 Cytokine / chemokine receptors 1234 CDw197 CCR7 Cytokine / chemokine receptors 1236 CD200 OX2 Non-lineage molecules 4345 CD201 EPC R Endothelial cells 10544 CD202b Tie2 (Tek) Endothelial cells 7010 CD203c NPP3 / PDNP3 Myeloid cells 5169 CD204 Macrophage scavenger R Myeloid cells 4481 CD205 DEC205 Dendritic cells 4065 CD206 Macrophage mannose R Dendritic cells 4360 CD207 Langerin Dendritic cells 50489 CD208 DC-LAMP Dendritic cells CD209 DC-SIGN Dendritic cells 30385 CDw210 IL-10R Cytokine / chemokine receptors 3587; 3588 CD212 IL-12 R Cytokine / chemokine receptors 3594 CD213a1 IL-13 R alpha 1 Cytokine / chemokine receptors 3597 CD213a2 IL-13 R alpha 2 Cytokine / chemokine receptors 3598 CDw217 IL-17 R Cytokine / chemokine receptors 23765 CD220 Insulin R Non-lineage molecules 3643 CD221 IGF1 R Non-lineage molecules 3480 CD222 Mannose-6-phosphate / IGF2 R Non-lineage molecules 3482 CD223 LAG-3 Non-lineage molecules 3902 CD224 Gamma-glutamyl transferase Non-lineage molecules 2678 CD225 Leu13 Non-lineage molecules 8519 CD226 DNAM-1 (PTA1) T cells 10666 CD227 MUC.1 Non-lineage molecules 4582 CD228 Melanotransferrin Non-lineage molecules 4241 CD229 Ly9 Non-lineage molecules 4063 CD230 Prion protein Non-lineage molecules 5621 CD231 TALLA-1 / A15 Non-lineage molecules 7102 CD232 VESP R Non-lineage molecules 10154 CD233 Band 3 Erythroid cells 6521 CD234 Fy-glycoprotein (DARC) Erythroid cells 2532 CD235a Glycophorin A Erythroid cells 2993 CD235b Glycophorin B Erythroid cells 2994 CD235ab Glycophorin A / B crossreactive mAb Erythroid cells CD236 Glycophorin C / D Erythroid cells CD236R Glycophorin C Erythroid cells 2995 CD238 Kell Erythroid cells 3792 CD239 B-CAM Erythroid cells 4059 CD240CE Rh30CE Erythroid cells 6006 CD240D Rh30D Erythroid cells 6007 CD240DCE Rh30D / CE crossreactive mAb Erythroid cells CD241 RhAg Erythroid cells 6005 CD242 ICAM-4 Erythroid cells 3386 CD243 MDR-1 Stem / progenitor cells CD244 2B4 NK cells 51744 CD245 p220 / 240 T cells CD246 Anaplastic lymphoma kinase T cells 238 CD247 Zeta chain T cells 919 Plans are well advanced for the 8th Workshop, to be organized in Adelaide in 2004 under the aegis of Prof. H. Zola (see: www.hlda8.org). It is sometimes assumed that the catalogue of surface molecules associated with human hemopoietic cells is now essentially complete, but there is abundant evidence in the literature for novel surface molecules that would merit study at the next Workshop, and that could provide the basis for new CD designations. Table 3 comprises a list of potential new molecules reported following the production of monoclonal antibodies, and also a more extensive list of surface molecules identified via gene cloning. In most instances, no antibodies are available against the putative new leucocyte / endothelial markers in this latter group. Specific and well characterised reagents, whether monoclonal or polyclonal, are needed not only for detecting these new "virtual" molecules but also for defining functional domains, for characterizing 3D protein structure, and for analyzing protein-protein interactions. It may be added that cloning of gene sequences often reveals multiple members of new or existing molecular families (e. g., the Toll-like receptors) and may identify surface receptors that bind more than one ligand or vice versa, (e. g. the TALL-1 and APRIL ligands for TACI and BCMA). Furthermore, a number of leukocyte-associated markers have been cloned from mice and other species, and almost all will have human homologues. The 8th Workshop will provide a forum for a range of antibody-based studies based on this accumulating corpus of genomic and proteomic data. As in the 7th Workshop, in which four new sections were added, it may be possible to include neuronal cells in the 8th Workshop. Many neuronal cells express cell surface proteins found on leukocytes and vice versa (e. g., CD56, CD171, CD100, CDD168). Furthermore, the guidance cues used by neuronal cells share similarities to those involved in leukocyte extravasation, so the expression of these molecules in common may reflect shared biological processes. CD designation Name The ILT / LIR family CD85a ILT5 / LIR3 CD85b ILT8 CD85c LIR8 CD85d ILT4 / LIR2, MIR10 CD85e ILT6 / LIR4 CD85f ILT11 CD85g ILT7 CD85h ILT1 / LIR7 CD85i LIR6 CD85j ILT2 / LIR1, MIR7 CD85k ILT3 / LIR5 CD85l ILT9 CD85m ILT10 The KIR family CD158z KIR3DL7 / KIRC1 CD158b1 and CD158b2 KIR2DL2 / p58.2 and KIR2DL3 / p58.3 CD158a KIR2DL1 / p58.1 CD158c KIR2DS6 / KIRX CD158d KIR2DL4 CD158e1 KIR3DL1 / p70 CD158e2 KIR3DS1 / p70 CD158f KIR2DL5 CD158g KIR2DS5 CD158h KIR2DS1 / p50.1 CD158i KIR2DS4 / p50.3 CD158j KIR2DS2 / p50.2 CD158k KIR3DL2 / p140 Molecule Mol. Size Cell types Comments References Identified following antibody production AM-3K antigen 70 and 120 kDa Macrophages Zeng, L. et al., J. Pathol. 1996. 178: 207. BDCA-2, BDCA-3, and BDCA-4 antigens Dendritic cells Identifies subsets of dendritic cells Dzionek, A., et al., J. Immunol. 2000. 165: 6037. BENE 17 kDa Endothelium "Raft-associated" member of MAL family. Interacts with caveolin-1 de Marco M.C. et al., J. Biol. Chem. 2001. 276: 23009. CMRF-44 ? Dendritic cells Differentiated/Activated Hock, B.D. et al., Immunology. 1994. 83: 573. CMRF-56 95 Dendritic cells Differentiated/Activated Hock, B.D. et al., Tissue Antigens. 1999. 53: 320. H47 antigen 100 kDa (non red.) 120 kDa (red.) T cells & most NK, B cells and monocytes ? Involved in T cell activation Hirohashi, N. et al., Cell Immunol. 1993. 152: 371 Hal-1 200 kDa (100 kDa) T cells, EBV-transformed B cells, myelomonocytic cells, anaplastic large cell lymphoma ? New lymphoma marker Asanuma, H. et al., Br. J. Haematol. 1999, 106: 55. LAK1 and LAK2 antigens 120 kDa and 110 + 140 kDa, respectively LGL and LAK cells Zocchi, M. R. et al., Cell Immunol. 1989, 124: 144. NKp80 80 kDa dimer NK cells and CD56-positive T cells Novel member of the killer cell lectin-like receptor gene family, encoded by KLRF1 gene. Triggers NK cell cytotoxicity. Vitale, M. et al.,Eur. J. Immunol. 2001, 31: 233. Roda-Navarro, P. et al., Eur. J. Immunol. 2000, 30: 568 VAP-1 (Vascular adhesion protein) 90 kDa Endothelium Mediates lymphocyte-endothelial adhesion. Has monoamine oxidase activity Bono, P. et al., J. Immunol. 1998, 160: 5563. Salmi, M. and Jalkanen, S. Science 1992, 257: 1407. Wue-1 antigen 94 kDa Plasma cells Stimulates growth of plasma cells Greiner, A. et al., Virchows Arch. 2000, 437: 372. Identified via gene cloning B cell maturation factor (BCMA) 184 aa B cells TNFR family member. Receptor for TALL-1 and APRIL Madry C., et al., Int. Immunol. 1998, 10: 1693. Shu, H. B. and Johnson, H., Proc. Natl. Acad. Sci. USA 2000, 97: 9156 B7-H2 302 aa Dendritic cells New member of B7 family. Binds ICOS on activated T cells Wang, S. et al., Blood 2000, 96: 2808. CLEC-1 280 aa Dendritic cells Novel C-type lectin-like receptor with cytoplasmic tyrosine-based motif Colonna, M. et al., Eur. J. Immunol. 2000, 30: 697. CMRF-35A CMRF-35H 224 aa 300aa NK cells, neutrophils, monocytes, dendritic cells and subset of T lymphocytes Novel Ig superfamily receptors. CMRF-35H contains 3 cytoplasmic tyrosine based motifs Jackson, D. G. et al., Eur. J. Immunol. 1992. 22: 1157. Green et al., Int. Immunol. 1998. 10: 891. CS1 NK cells Novel receptor belonging to CD2 subset of Ig superfamily Boles, K. S. et al., Immunogenetics 2001, 52: 302. DC-STAMP 470 aa Dendritic cells Novel protein containing seven putative transmembrane domains Hartgers, F. C. et al., Eur. J. Immunol. 2000, 30: 3585. EMR3 652 aa Mainly leukocyte restricted. Highest levels on neutrophils, monocytes and macrophages Novel EGF-TM7 molecule. Interacts with a surface ligand on myeloid cells Stacey, M. et al., J. Biol. Chem. 2001, 276: 18863. Flt-1 (VEGFR-1) Endothelial cells, monocytes Sawano, A. et al., Blood 2001, 97: 785. GPRv53 390 aa Leukocytes Identified by gene cloning. G-protein-coupled histamine receptor Oda, T. et al., J. Biol. Chem. 2000, 275: 36781. IRTA1 and IRTA2 Subpopulations of B cells Homologous to the Fc and inhibitory receptor families Hatzivassiliou, G. et al. Immunity 2001, 14: 277. M160 1453 aa Macrophages New member of scavenger receptor cysteine-rich superfamily Gronlund, J. et al., J. Immunol. 2000, 165: 6406. MARCO (Macrophage receptor with collagenous structure) 520 aa Macrophages Class A scavenger receptor. Involved in bacterial clearance in vivo Elomaa et al., J. Biol. Chem. 1998, 273: 4530. Van der Laan LJ et al., J. Immunol. 1999, 162: 939. TACI 293 aa B cells TNFR family member. Receptor for TALL-1 and APRIL Xia, X. Z. et al., J. Exp. Med. 2000, 192: 137. TREM-1 and TREM-2 (Triggering receptors expressed on myeloid cells) Neutrophils and subset of monocytes (TREM-1) and macrophages (TREM-2) Novel Ig superfamily receptors. TREM-1 triggersneutrophil secretion (e. g. IL-8) and degranulation. TREM-2 activates macrophages. Both associate with DAP12 Bouchon, A. et al., J. Immunol. 2000, 164: 4991. Daws, M. R. et al., Eur. J. Immunol. 2001, 31: 783. Finally, it remains to be established how the 8th and subsequent HLDA Workshops should deal with lineage- or stage-restricted leucocyte molecules that are localized within the cell cytoplasm (or nucleus). Given the importance of many of these molecules in signaling pathways initiated via known surface CD molecules, their identification and study is an inevitable extension of the work of the first seven HLDA Workshops. Whether or not a new "intracellular CD" categorization scheme is devised for such molecules, they are of interest for many laboratories interested in human hematopoietic cells, and their study will be among the aims of the next Workshop.