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GENE_NAME : CD2
CD_NAME : CD2
DESC: CD2 antigen (p50); sheep red blood cell receptor
OTH_NAMES: SRBC; T11CLONE_NAME ISO_TYPE SUBMITTER AVAILABLE_FROM LT2 IgG2b Filatov AbD Serotec RPA-2.10 IgG1k Aversa BD Biosciences 1E7E8 IgG2a Tinsley Novus Biologicals LT2 IgG2b Tinsley Novus Biologicals RPA-2.10 IgG1k Tinsley Novus Biologicals TS1/8 IgG1 Tinsley Novus Biologicals TS2/18.1.1 IgG1 Tinsley Novus Biologicals RPA-2.10 IgG1k Aversa BioLegend RPA-2.10 IgG1k Aversa AbD Serotec RPA-2.10 IgG1k Aversa Thermo Fisher Scientific TS1/8 BioLegend TS1/8 Mouse IgG1 kappa EXBIO Praha LT2 Mouse IgG2b Filatov EXBIO Praha MEM-65 Mouse IgG1 Horejsi EXBIO Praha -
CLONE_NAME ISO_TYPE SUBMITTER AVAILABLE_FROM 1E7E8 IgG2a Fox 1MONO2A6 IgG3 Reinherz 6F10.3 IgG1 Mawas 7A9 IgM Reinherz 37994 IgG2b Naito 38025 IgM Naito 9.6 IgG2a Kamoun MM 35.1 IgG2a Martin PJ 39B21 IgG2a Mawas 39C1.5 IgG2a Mawas 39C8.18 unknown Mawas 39H7.3 unknown Mawas 41F2.1 unknown Mawas 95-5-49 unknown Quinones AICD2.1 IgG2a Meuer B-E2 IgG2b Wijdenes CD2X11 IgG1 Boumsell CLB-T11.1/1 IgG1 van Lier CLB-T11/1 IgG1 Tetteroo CLB-T11.2/1 IgG1 van Lier CTAG-CD2, G11 IgG1 Johnson D66/1 IgG2b Bernard D66 (??) IgM Bernard D66 clone1 (??) IgM Bernard F92-3A11 (S-T21) IgG1 Poncelet F110.08 IgG1 Plesner GT2 IgG1 Bernard HIT11 IgG1 Chen JN-20-5 unknown Bai JOR-T2 IgG2b Amador L303 IgG2a Maino Leu-5b IgG2ak Warner Leu-5D IgG1 Becton Dickinson LT2 IgG2b Filatov AbD Serotec M-T26 IgG1 Rieber M-T110 unknown Rieber M-T201 IgG1 Rieber M-T910 IgG1 Rieber M-T1110 IgG1 Rieber MEM-65 IgG1 Horejsi NU-T1 IgG1 Sagawa NU-TER IgG1 Yokoyama O275 IgG1 Bernard OCH.217 IgM Colombani OKT11 IgG2a Ortho OR 101 IgG1 Gazit RPA-2.10 IgG1k Aversa BD Biosciences SA1-11 IgG1 Yang T11 IgG1 Coulter T11 /3PT2H9 IgG1 Meuer SC T11 /3T4-8B5 IgG2a Reinherz T11 /7E10 IgG2b Reinherz T11 /7T4-7A9 IgM Reinherz T11 /7T4-7E10 IgG2b Reinherz T11 /7T47E10 IgG2b Reinherz T11 /ROLD2-1H8 IgG1 Reinherz T56 IgM Maeda T57 IgG Maeda T411B5 IgG ?? Girardet TS1/8.1.1 IgG1 Springer TS2/18.1.1 IgG1 Springer WuT11-1 IgG1 Bin X/3 unknown Pulford XIX.8 IgG2b Bourel 1E7E8 IgG2a Tinsley Novus Biologicals LT2 IgG2b Tinsley Novus Biologicals RPA-2.10 IgG1k Tinsley Novus Biologicals TS1/8 IgG1 Tinsley Novus Biologicals TS2/18.1.1 IgG1 Tinsley Novus Biologicals RPA-2.10 IgG1k Aversa BioLegend RPA-2.10 IgG1k Aversa AbD Serotec RPA-2.10 IgG1k Aversa Thermo Fisher Scientific TS1/8 BioLegend TS1/8 Mouse IgG1 kappa EXBIO Praha LT2 Mouse IgG2b Filatov EXBIO Praha MEM-65 Mouse IgG1 Horejsi EXBIO Praha -
STRUCTURE
CD2 is a type 1 protein with two immunoglobulin superfamily (IgSF) domains. The N-terminal domain is the ligand binding domain.1 It has five proline-rich stretches in its cytoplasmic tail involved in signal transduction.2-4
1. Gray F, Cyster JG, Willis AC, Barclay AN, Williams AF. Structural analysis of the CD2 T lymphocyte antigen by site-directed mutagenesis to introduce a disulphide bond into domain 1. Protein Eng. 1993;6:965-70.2. Bell GM, Fargnoli J, Bolen JB, Kish L, Imboden JB. The SH3 domain of p56lck binds to proline-rich sequences in the cytoplasmic domain of CD2. J Exp Med. 1996;183:169-78.3. King PD, Sadra A, Teng JM, Bell GM, Dupont B. CD2-mediated activation of the Tec-family tyrosine kinase ITK is controlled by proline-rich stretch-4 of the CD2 cytoplasmic tail. Int Immunol. 1998;10:1009-16.4. Dustin ML, Olszowy MW, Holdorf AD, Li J, Bromley S, Desai N, Widder P, Rosenberger F, van der Merwe PA, Allen PM, Shaw AS. A novel adaptor protein orchestrates receptor patterning and cytoskeletal polarity in T-cell contacts. Cell.1998;94:667-77. -
LIGANDS
Extracellular
CD58 in humans.1,2 CD48 in rodents.3-5Intracellular associate molecules
Fyn, Lck, CD2AP, CD2BP1 and CD2BP2.6-9
1. Ikemizu S, Sparks LM, van der Merwe PA, Harlos K, Stuart DI, Jones EY, Davis SJ. Crystal structure of the CD2-binding domain of CD58 (lymphocyte function-associated antigen 3) at 1.8-A resolution. Proc Natl Acad Sci U S A. 1999;96:4289-94.2. Wang JH, Smolyar A, Tan K, Liu JH, Kim M, Sun ZY, Wagner G, Reinherz EL. Structure of a heterophilic adhesion complex between the human CD2 and CD58 (LFA-3) counterreceptors. Cell. 1999;97:791-803.3. Kato K, Koyanagi M, Okada H, Takanashi T, Wong YW, Williams AF, Okumura K, Yagita H. CD48 is a counter-receptor for mouse CD2 and is involved in T cell activation. J Exp Med. 1992;176(5):1241-9.4. Davis SJ, Ikemizu S, Wild MK, van der Merwe PA. CD2 and the nature of protein interactions mediating cell-cell recognition. Immunol Rev. 1998;163:217-36.5. Zhu B, Davies EA, van der Merwe PA, Calvert T, Leckband DE. Direct measurements of heterotypic adhesion between the cell surface proteins CD2 and CD48. Biochemistry. 2002;41:12163-70.6. Carmo AM, Mason DW, Beyers AD. Physical association of the cytoplasmic domain of CD2 with the tyrosine kinases p56lck and p59fyn. Eur J Immunol. 1993;23:2196-201.7. Dustin ML, Olszowy MW, Holdorf AD, Li J, Bromley S, Desai N, Widder P, Rosenberger F, van der Merwe PA, Allen PM, Shaw AS. A novel adaptor protein orchestrates receptor patterning and cytoskeletal polarity in T-cell contacts. Cell. 1998;94:667-77.8. Freund C, Kühne R, Yang H, Park S, Reinherz EL, Wagner G. Dynamic interaction of CD2 with the GYF and the SH3 domain of compartmentalized effector molecules. EMBO J. 2002;21:5985-95.9. Yang H, Reinherz EL. CD2BP1 modulates CD2-dependent T cell activation via linkage to protein tyrosine phosphatase (PTP)-PEST. J Immunol. 2006;176:5898-907.
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GENE_NAME : CD2
CD_NAME : CD2
It is expressed at high density on thymocytes, T-cells and on NK cells. It is one of the earliest markers expressed in T-cell development. CD2 is also expressed on mast cells, a subset of thymic B cells and dendritic cells.1-3
1. Hauswirth AW, Florian S, Schernthaner GH, Krauth MT, Sonneck K, Sperr WR, Valent P. Expression of cell surface antigens on mast cells: mast cell phenotyping. Methods Mol Biol. 2006;315:77-90.2. Punnonen J, de Vries JE. Characterization of a novel CD2+ human thymic B cell subset. J Immunol. 1993;151:100-10.3. Crawford K, Stark A, Kitchens B, Sternheim K, Pantazopoulos V, Triantafellow E, Wang Z, Vasir B, Larsen CE, Gabuzda D, Reinherz E, Alper CA. CD2 engagement induces dendritic cell activation: implications for immune surveillance and T-cell activation. Blood. 2003;102:1745-52.
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GENE_NAME : CD2
CD_NAME : CD2
CD2 functions as an adhesion, between T cells and antigen-presenting cells or NK cells and target cells, and costimulatory molecule. CD2 is not essential for the development and function of T cells.1 It has been shown to regulate TCR-affinity thresholds for T cell activation.2
CD2 colocalize with TCR in the center of the immne synapse, recruiting and activating several intracellular molecules, increasing T and NK cell signaling and cytotoxicity.3-5
1. Killeen N, Stuart SG, Littman DR. Development and function of T cells in mice with a disrupted CD2 gene. EMBO J. 1992;11:4329-36.2. van der Merwe PA. A subtle role for CD2 in T cell antigen recognition. J Exp Med. 1999;190:1371-4.3. Singleton K, Parvaze N, Dama KR, Chen KS, Jennings P, Purtic B, Sjaastad MD, Gilpin C, Davis MM, Wülfing C. A large T cell invagination with CD2 enrichment resets receptor engagement in the immunological synapse. J Immunol. 2006;177:4402-13.4. Espagnolle N, Depoil D, Zaru R, Demeur C, Champagne E, Guiraud M, Valitutti S. CD2 and TCR synergize for the activation of phospholipase Cgamma1/calcium pathway at the immunological synapse. Int Immunol. 2007;19:239-48.5. Kaizuka Y, Douglass AD, Vardhana S, Dustin ML, Vale RD. The coreceptor CD2 uses plasma membrane microdomains to transduce signals in T cells. J Cell Biol. 2009;185:521-34.6. Leitner J, Herndler-Brandstetter D, Zlabinger GJ, Grubeck-Loebenstein B, Steinberger P. CD58/CD2 Is the Primary Costimulatory Pathway in Human CD28-CD8+ T Cells. J Immunol. 2015;195:477-87.
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Cell markerGENE_NAME : CD2
CD_NAME : CD2
Useful as a T and NK cell marker.
Therapeutic
Phenotypic typing and NK cell and T leukemias and lymphomas.1-3 CD2 is expressed on neoplastic mast cells.4 Myeloma cells also express significant levels of CD2.5
Siplizumab (MEDI-507) is humanized monoclonal antibody against CD2 molecule that has been studied for the treatment of severe psoriasis and for prophylaxis of GvHD because of its T-cell depleting properties.6-8 Phase I/II trial of slipizumab in patients with malignant T-cell lymphoproliferative disorders have been initiated.9
Alefacept (Amevive) is a CD58-immunoglobulin (Ig) Fc fusion protein that binds to CD2. It has been approved for the treatment of psoriasis.10 Recently, it has been tested for the treatment of insulin-dependent diabetes.11
1. Kwong YL. Natural killer-cell malignancies: diagnosis and treatment. Leukemia. 2005;19:2186-94.2. Cortelazzo S, Ponzoni M, Ferreri AJ, Hoelzer D. Lymphoblastic lymphoma. Crit Rev Oncol Hematol. 2011;79:330-43.3. Ohshima K. Molecular Pathology of Adult T-Cell Leukemia/Lymphoma. Oncology. 2015;89 Suppl 1:7-15.4. Escribano L, Díaz-Agustín B, Núñez R, Prados A, Rodríguez R, Orfao A. Abnormal expression of CD antigens in mastocytosis. Int Arch Allergy Immunol. 2002;127:127-32.5. Ruiz-Argüelles GJ, San Miguel JF. Cell surface markers in multiple myeloma. Mayo Clin Proc. 1994;69:684-90.6. Bissonnette R, Langley RG, Papp K, Matheson R, Toth D, Hultquist M, Geba GP, White B. Humanized anti-CD2 monoclonal antibody treatment of plaque psoriasis: efficacy and pharmacodynamic results of two randomized, double-blind, placebo-controlled studies of intravenous and subcutaneous siplizumab. Arch Dermatol Res. 2009;301:429-42.7. Langley RG, Papp K, Bissonnette R, Toth D, Matheson R, Hultquist M, White B. Safety profile of intravenous and subcutaneous siplizumab, an anti-CD2 monoclonal antibody, for the treatment of plaque psoriasis: results of two randomized, double-blind, placebo-controlled studies. Int J Dermatol. 2010;49:818-28.8. Brochstein JA, Grupp S, Yang H, Pillemer SR, Geba GP. Phase-1 study of siplizumab in the treatment of pediatric patients with at least grade II newly diagnosed acute graft-versus-host disease. Pediatr Transplant. 2010;14:233-41.9. O'Mahony D, Morris JC, Stetler-Stevenson M, Matthews H, Brown MR, Fleisher T, Pittaluga S, Raffeld M, Albert PS, Reitsma D, Kaucic K, Hammershaimb L, Waldmann TA, Janik JE. EBV-related lymphoproliferative disease complicating therapy with the anti-CD2 monoclonal antibody, siplizumab, in patients with T-cell malignancies. Clin Cancer Res. 2009;15:2514-22.10. Chamian F, Lowes MA, Lin SL, Lee E, Kikuchi T, Gilleaudeau P, Sullivan-Whalen M, Cardinale I, Khatcherian A, Novitskaya I, Wittkowski KM, Krueger JG. Alefacept reduces infiltrating T cells, activated dendritic cells, and inflammatory genes in psoriasis vulgaris. Proc Natl Acad Sci U S A. 2005;102:2075-80.11. Rigby MR, Harris KM, Pinckney A, DiMeglio LA, Rendell MS, Felner EI, Dostou JM, Gitelman SE, Griffin KJ, Tsalikian E, Gottlieb PA, Greenbaum CJ, Sherry NA, Moore WV, Monzavi R, Willi SM, Raskin P, Keyes-Elstein L, Long SA, Kanaparthi S, Lim N, Phippard D, Soppe CL, Fitzgibbon ML, McNamara J, Nepom GT, Ehlers MR. Alefacept provides sustained clinical and immunological effects in new-onset type 1 diabetes patients. J Clin Invest. 2015;125:3285-96.
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GENE_NAME : CD2
CD_NAME : CD2
GENERAL_INFORMATION
NCBI_NAME CD2 NCBI_OTHER_NAME SRBC; T11 SWISS_NAMES CD2_HUMAN DESC CD2 antigen (p50); sheep red blood cell receptor LOCUS_INFO_LINKS
HGNC_LOCUS_TAG: 1639 ONLINE_MENDELIAN_INHERITANCE: 186990 NCBI_HOMOLOGENE: 1338 NCBI_MAP: 1p13 NCBI_ENTRE_GENE_ENTRY: 914 GENE_SIZE: 14750 EN_GE_EN: MRNA_SEQ_LENGTH: 1579 PRCORENC: 14 to 1069 ENTREN: ENST00000369478 PROTEIN_LENGTH_NCBI_REFSEQ: 352 NCBI_REF_SEF_ENTRY: NP_001758 , 4502653 PROTEIN_LENGTH_SWISPROT: 351 ENSEMBLE_PROT_ENTRY: ENSP00000358490 PR_MO_WEIGHT: 39439 SWPROT_PROTEIN_ENTRY: CD2_HUMAN , P06729 PR_SW_PR: 10.00 IPI_NUMBER: IPI00027484 NCBI_CONSV_DOMAINS: 4502653 ENSM_NUMBER: P06729
