cd2 antigens


Summary: Glycoprotein members of the immunoglobulin superfamily which participate in T-cell adhesion and activation. They are expressed on most peripheral T-lymphocytes, natural killer cells, and thymocytes, and function as co-receptors or accessory molecules in the T-cell receptor complex.

Top Publications

  1. Martelli M, Lin H, Zhang W, Samelson L, Bierer B. Signaling via LAT (linker for T-cell activation) and Syk/ZAP70 is required for ERK activation and NFAT transcriptional activation following CD2 stimulation. Blood. 2000;96:2181-90 pubmed
    ..These data suggest that LAT is an adapter protein important for the regulation of CD2-mediated T-cell activation. ..
  2. Sasada T, Reinherz E. A critical role for CD2 in both thymic selection events and mature T cell function. J Immunol. 2001;166:2394-403 pubmed
    ..Collectively, these findings show that CD2 plays a role in pre-TCR function in double-negative thymocytes, TCR selection events during thymocyte development, and TCR-stimulated cytokine production in mature T cells. ..
  3. Green J, Karpitskiy V, Kimzey S, Shaw A. Coordinate regulation of T cell activation by CD2 and CD28. J Immunol. 2000;164:3591-5 pubmed
    ..This suggests that CD2 and CD28 may function together to facilitate interactions of the T cell and APC, allowing for efficient signal transduction through the TCR. ..
  4. Damschroder M, Kozhich A, Woods R, Cheng L, Mullikin B, Wilson S, et al. Analysis of human and primate CD2 molecules by protein sequence and epitope mapping with anti-human CD2 antibodies. Mol Immunol. 2004;41:985-1000 pubmed publisher
  5. Douglass A, Vale R. Single-molecule microscopy reveals plasma membrane microdomains created by protein-protein networks that exclude or trap signaling molecules in T cells. Cell. 2005;121:937-50 pubmed
    ..Our data suggest that diffusional trapping through protein-protein interactions creates microdomains that concentrate or exclude cell surface proteins to facilitate T cell signaling. ..
  6. Gebauer M, von Melchner H, Beckers T. Genomewide trapping of genes that encode secreted and transmembrane proteins repressed by oncogenic signaling. Genome Res. 2001;11:1871-7 pubmed
    ..Molecular analysis of six randomly chosen integrations revealed that, in each case, U3Ceo captured a signal sequence from proteins involved in oncogenic transformation and metastatic spread. ..
  7. Dustin M. Adhesive bond dynamics in contacts between T lymphocytes and glass-supported planar bilayers reconstituted with the immunoglobulin-related adhesion molecule CD58. J Biol Chem. 1997;272:15782-8 pubmed
    ..These findings have implications for the mechanism of signaling by CD2 and the mechanism of cell detachment from large numbers of transient interactions. ..
  8. Lynn D, Freeman A, Murray C, Bradley D. A genomics approach to the detection of positive selection in cattle: adaptive evolution of the T-cell and natural killer cell-surface protein CD2. Genetics. 2005;170:1189-96 pubmed
    ..Moreover, we show that selection has operated primarily on the extracellular domain of CD2 and discuss the implications of this for an important regulator of the adaptive immune response. ..
  9. Brossay A, Hube F, Moreau T, Bardos P, Watier H. Porcine CD58: cDNA cloning and molecular dissection of the porcine CD58-human CD2 interface. Biochem Biophys Res Commun. 2003;309:992-8 pubmed
    ..These structural data will help us to develop poCD58 blocking agents for xenotransplantation. ..

More Information


  1. Davis S, Ikemizu S, Wild M, van der Merwe P. CD2 and the nature of protein interactions mediating cell-cell recognition. Immunol Rev. 1998;163:217-36 pubmed
    ..The crystallographic analysis of the CD2-binding domain of CD58 strongly supports this concept. ..
  2. Orange J, Harris K, Andzelm M, Valter M, Geha R, Strominger J. The mature activating natural killer cell immunologic synapse is formed in distinct stages. Proc Natl Acad Sci U S A. 2003;100:14151-6 pubmed
    ..Thus the process of CD2, CD11a, CD11b, and F-actin accumulation in the pSMAC and perforin accumulation in the central SMAC of the NKIS are sequential processes with distinct cytoskeletal requirements. ..
  3. Wang J. Protein recognition by cell surface receptors: physiological receptors versus virus interactions. Trends Biochem Sci. 2002;27:122-6 pubmed
    ..Viruses might take advantage of this low affinity to invade a host cell by evolving a stronger binding affinity to the surface receptors than that associated with physiological ligands. Structural data appear to support this notion. ..
  4. Shimojima M, Nishimura Y, Miyazawa T, Kato K, Nakamura K, Izumiya Y, et al. A feline CD2 homologue interacts with human red blood cells. Immunology. 2002;105:360-6 pubmed
    ..These results are indicative of the similarity of feline and human CD2 structures. fCD2 was found to be expressed in feline peripheral blood T lymphocytes, monocytes and cultured lymphoid cells...
  5. Nishizawa K, Freund C, Li J, Wagner G, Reinherz E. Identification of a proline-binding motif regulating CD2-triggered T lymphocyte activation. Proc Natl Acad Sci U S A. 1998;95:14897-902 pubmed
    ..Hence, a proline-binding module distinct from SH3 and WW domains regulates protein-protein interactions. ..
  6. Dustin M, Olszowy M, Holdorf A, Li J, Bromley S, Desai N, et al. A novel adaptor protein orchestrates receptor patterning and cytoskeletal polarity in T-cell contacts. Cell. 1998;94:667-77 pubmed
    ..This novel protein, called CD2AP, is likely to facilitate receptor patterning in the contact area by linking specific adhesion receptors to the cytoskeleton. ..
  7. Lin Z, Fillmore G, Um T, Elenitoba Johnson K, Lim M. Comparative microarray analysis of gene expression during activation of human peripheral blood T cells and leukemic Jurkat T cells. Lab Invest. 2003;83:765-76 pubmed
  8. Boysen P, Olsen I, Berg I, Kulberg S, Johansen G, Storset A. Bovine CD2-/NKp46+ cells are fully functional natural killer cells with a high activation status. BMC Immunol. 2006;7:10 pubmed
    ..These results provide evidence that bovine CD2- as well as CD2+ cells of the NKp46+ phenotype are fully functional NK cells, the CD2- subset showing signs of being more activated in the circulation. ..
  9. van der Merwe P, Davis S. Molecular interactions mediating T cell antigen recognition. Annu Rev Immunol. 2003;21:659-84 pubmed
    ..These studies provide the necessary framework for exploring how these molecular interactions initiate T cell activation. ..
  10. Vesosky B, Turner O, Turner J, Orme I. Activation marker expression on bovine peripheral blood gammadelta T cells during post-natal development and following vaccination with a commercial polyvalent viral vaccine. Dev Comp Immunol. 2003;27:439-47 pubmed
  11. McNerney M, Kumar V. The CD2 family of natural killer cell receptors. Curr Top Microbiol Immunol. 2006;298:91-120 pubmed
    ..This review discusses these multiple roles for CD2 family members, focusing specifically on the regulation of NK cells. ..
  12. Hutchings N, Clarkson N, Chalkley R, Barclay A, Brown M. Linking the T cell surface protein CD2 to the actin-capping protein CAPZ via CMS and CIN85. J Biol Chem. 2003;278:22396-403 pubmed
    ..These adaptor proteins are important in T cell signaling consistent with a role for CD2 in regulating pathways initiated by CMS/CIN85 and CAPZ. ..
  13. De Jager P, Baecher Allan C, Maier L, Arthur A, Ottoboni L, Barcellos L, et al. The role of the CD58 locus in multiple sclerosis. Proc Natl Acad Sci U S A. 2009;106:5264-9 pubmed publisher
  14. Saveliev A, Everett C, Sharpe T, Webster Z, Festenstein R. DNA triplet repeats mediate heterochromatin-protein-1-sensitive variegated gene silencing. Nature. 2003;422:909-13 pubmed
  15. Liu J, Chow V, Jois S. A novel, rapid and sensitive heterotypic cell adhesion assay for CD2-CD58 interaction, and its application for testing inhibitory peptides. J Immunol Methods. 2004;291:39-49 pubmed
    ..This method was successfully applied for testing inhibitory peptides to CD2-CD58 interaction. ..
  16. Bachmann M, Barner M, Kopf M. CD2 sets quantitative thresholds in T cell activation. J Exp Med. 1999;190:1383-92 pubmed
    ..Thus, CD2 sets quantitative thresholds and fine-tunes T cell activation both in vitro and in vivo. ..
  17. Koo H, Park Y, Hamilton M, Barrington G, Davies C, Kim J, et al. Analysis of the immune response to Mycobacterium avium subsp. paratuberculosis in experimentally infected calves. Infect Immun. 2004;72:6870-83 pubmed
    ..The studies clearly show multicolor FC offers a consistent reliable way to monitor the evolution and changes in the immune response to M. avium subsp. paratuberculosis that occur during disease progression. ..
  18. Wang J, Smolyar A, Tan K, Liu J, Kim M, Sun Z, et al. Structure of a heterophilic adhesion complex between the human CD2 and CD58 (LFA-3) counterreceptors. Cell. 1999;97:791-803 pubmed
    ..These features explain CD2-CD58 dynamic binding, offering insights into interactions of related immunoglobulin superfamily receptors. ..
  19. Cleverley S, Henning S, Cantrell D. Inhibition of Rho at different stages of thymocyte development gives different perspectives on Rho function. Curr Biol. 1999;9:657-60 pubmed
  20. Depoil D, Zaru R, Guiraud M, Chauveau A, Harriague J, Bismuth G, et al. Immunological synapses are versatile structures enabling selective T cell polarization. Immunity. 2005;22:185-94 pubmed
    ..The combination of sustained signaling with preferential and rapid polarization provides a mechanism for the high sensitivity and selectivity of T cell responses. ..
  21. Loza M, Luppi P, Kiefer K, Martin E, Szczytkowski J, Perussia B. Human peripheral CD2-/lo T cells: an extrathymic population of early differentiated, developing T cells. Int Immunol. 2005;17:1213-25 pubmed
  22. Killeen N, Stuart S, Littman D. Development and function of T cells in mice with a disrupted CD2 gene. EMBO J. 1992;11:4329-36 pubmed
    ..Within the context of other targetted mutations, these mice should be useful in defining the precise roles of various cell surface molecules involved in T cell responses. ..
  23. Teh S, Killeen N, Tarakhovsky A, Littman D, Teh H. CD2 regulates the positive selection and function of antigen-specific CD4- CD8+ T cells. Blood. 1997;89:1308-18 pubmed
    ..Furthermore, the results highlight the potential for a differential role for CD2 in thymocyte selection and T-cell immune responses. ..
  24. Bell G, Fargnoli J, Bolen J, Kish L, Imboden J. The SH3 domain of p56lck binds to proline-rich sequences in the cytoplasmic domain of CD2. J Exp Med. 1996;183:169-78 pubmed
    ..Thus, proline-rich sequences in the cytoplasmic domain of CD2 allow this transmembrane receptor to bind to the SH3 domain of p56lck. ..
  25. Schraven B, Samstag Y, Altevogt P, Meuer S. Association of CD2 and CD45 on human T lymphocytes. Nature. 1990;345:71-4 pubmed
    ..Using chemical crosslinking techniques, we now show that CD45 is linked to CD2 on the surface of human T lymphocytes. ..
  26. Robertson M, Caligiuri M, Manley T, Levine H, Ritz J. Human natural killer cell adhesion molecules. Differential expression after activation and participation in cytolysis. J Immunol. 1990;145:3194-201 pubmed
    ..These studies suggest that CAM play a central role in the regulation of NK cytolysis, and that changes in CAM expression may alter the target cell specificity of activated NK effectors. ..
  27. Hahn W, Menu E, Bothwell A, Sims P, Bierer B. Overlapping but nonidentical binding sites on CD2 for CD58 and a second ligand CD59. Science. 1992;256:1805-7 pubmed
    ..These observations suggest that direct interactions between CD2 and both CD58 and CD59 contribute to T cell activation and adhesion. ..
  28. Kato K, Koyanagi M, Okada H, Takanashi T, Wong Y, Williams A, et al. CD48 is a counter-receptor for mouse CD2 and is involved in T cell activation. J Exp Med. 1992;176:1241-9 pubmed
    ..These results indicate that CD48 is a ligand for mouse CD2 and is involved in regulating T cell activation. ..
  29. Lang G, Wotton D, Owen M, Sewell W, Brown M, Mason D, et al. The structure of the human CD2 gene and its expression in transgenic mice. EMBO J. 1988;7:1675-82 pubmed
  30. Evans C, Rall G, Killeen N, Littman D, Oldstone M. CD2-deficient mice generate virus-specific cytotoxic T lymphocytes upon infection with lymphocytic choriomeningitis virus. J Immunol. 1993;151:6259-64 pubmed
    ..Our results indicate that CD2 is not required for the generation of an LCMV-specific CTL response in vivo, nor is CD2 required for the maintenance or activation of memory CTL. ..
  31. Carmo A, Castro M, Arosa F. CD2 and CD3 associate independently with CD5 and differentially regulate signaling through CD5 in Jurkat T cells. J Immunol. 1999;163:4238-45 pubmed
    ..The modulation of CD5 phosphorylation may thus represent a level of regulation controlled by CD2 in signal transduction mechanisms in human T lymphocytes. ..
  32. Henschke S, Pawlowski N, Wild M, Kroesen A, Zeitz M, Hoffmann J. Lamina propria T cell activation: role of the costimulatory molecule CD2 and its cytoplasmic tail for the regulation of proliferation and apoptosis. Int J Colorectal Dis. 2006;21:321-31 pubmed
    ..The cytoplasmic tail of CD2 is not required, and CD45 appears to transmit apoptotic signals entering the T cell via CD2. ..
  33. Rouleau M, Mollereau B, Bernard A, Metivier D, Rosenthal Allieri M, Charpentier B, et al. CD2 induced apoptosis of peripheral T cells. Transplant Proc. 1997;29:2377-8 pubmed
  34. Hayes M, Sessions R, Brady R, Clarke A. Engineered assembly of intertwined oligomers of an immunoglobulin chain. J Mol Biol. 1999;285:1857-67 pubmed
    ..The ability of a protein molecule to form higher-order antiparallel structures is reminiscent of the behaviour of hairpins, duplexes, three-way and Holliday junctions in DNA. ..
  35. Kaito K, Otsubo H, Dobashi N, Usui N, Kobayashi M. CD2+ tetraploid acute promyelocytic leukemia variant with double (15;17) translocations. Int J Hematol. 2005;81:29-31 pubmed
    ..Double translocations were an additional abnormality in this case, and this patient's karyotype might have had some influence on morphological characteristics, expression of CD2, and poor clinical outcome. ..
  36. Zhang Z, Zhang M, Ravetch J, Goldman C, Waldmann T. Effective therapy for a murine model of adult T-cell leukemia with the humanized anti-CD2 monoclonal antibody, MEDI-507. Blood. 2003;102:284-8 pubmed
    ..These results demonstrate that MEDI-507 has therapeutic efficacy on ATL in vivo and provides support for a clinical trial involving this monoclonal antibody in the treatment of patients with CD2-expressing leukemias and lymphomas. ..
  37. Berney S, Schaan T, Wolf R, Van der Heyde H, Atkinson T. CD2 (OKT11) augments CD3-mediated intracellular signaling events in human T lymphocytes. J Investig Med. 2000;48:102-9 pubmed
    ..These results indicate that CD2 augments signaling through CD3, and consequently functions as a costimulatory molecule for resting T cells in the initial activation step. ..
  38. Kaleem Z, White G, Zutter M. Aberrant expression of T-cell-associated antigens on B-cell non-Hodgkin lymphomas. Am J Clin Pathol. 2001;115:396-403 pubmed
    ..Unless aggressive behavior is noted consistently, no aggressive treatment is justified. ..
  39. Snanoudj R, Rouleau M, Bidere N, Carmona S, Baron C, Latinne D, et al. A role for CD2 antibodies (BTI-322 and its humanized form) in the in vivo elimination of human T lymphocytes infiltrating an allogeneic human skin graft in SCID mice: an Fcgamma receptor-related mechanism involving co-injected human NK cells. Transplantation. 2004;78:50-8 pubmed
    ..The results are consistent with an FcgammaR-dependent ADCC mechanism mediated in vivo by human NK cells. ..
  40. Martelli M, Boomer J, Bu M, Bierer B. T cell regulation of p62(dok) (Dok1) association with Crk-L. J Biol Chem. 2001;276:45654-61 pubmed
  41. Elhmouzi Younes J, Boysen P, Pende D, Storset A, Le Vern Y, Laurent F, et al. Ovine CD16+/CD14- blood lymphocytes present all the major characteristics of natural killer cells. Vet Res. 2010;41:4 pubmed publisher
    ..Taken together, these findings led us to conclude that the ovine CD16(+)/CD14(-) lymphocyte sub-population displays the phenotype and functional characteristics of NK cells. ..
  42. Dustin M, Starr T, Coombs D, Majeau G, Meier W, Hochman P, et al. Quantification and modeling of tripartite CD2-, CD58FC chimera (alefacept)-, and CD16-mediated cell adhesion. J Biol Chem. 2007;282:34748-57 pubmed
    ..These results suggest that additional information is needed to correctly predict Alefacept-mediated bridge formation. ..
  43. Cheng Y, Foster B, Holland S, Klion A, Nutman T, Casale T, et al. CD2 identifies a monocyte subpopulation with immunoglobulin E-dependent, high-level expression of Fc epsilon RI. Clin Exp Allergy. 2006;36:1436-45 pubmed
    ..As such, this new description of CD2(high) monocytes as Fc epsilon RI-bearing cells suggests that they may be potential targets of anti-IgE immunomodulatory therapies. ..
  44. Chang H, Yi Q. Acute myeloid leukemia with pseudo-Chèdiak-Higashi anomaly exhibits a specific immunophenotype with CD2 expression. Am J Clin Pathol. 2006;125:791-4 pubmed
    ..9%) of 140 cases of newly diagnosed AML without PCH anomaly. CD2 expression correlated strongly with AML with PCH anomaly (P < .01), suggesting a link between a specific immunophenotypic marker, CD2, and AML with PCH anomaly. ..
  45. Langley R, Papp K, Bissonnette R, Toth D, Matheson R, Hultquist M, et al. 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 pubmed publisher
    ..V. or S.C. doses. Higher, clinically relevant doses of siplizumab would need to be tested to fully assess its safety. ..
  46. Yoneyama H, Matsuno K, Toda E, Nishiwaki T, Matsuo N, Nakano A, et al. Plasmacytoid DCs help lymph node DCs to induce anti-HSV CTLs. J Exp Med. 2005;202:425-35 pubmed
    ..pDC-derived IFN-alpha further stimulated the recovered LNDCs to induce CTLs. Therefore, the help provided by pDCs for LNDCs in primary immune responses seems to be pivotal to optimally inducing anti-HSV CTLs. ..
  47. Bimal S, Singh S, Das V, Sinha P, Gupta A, Bhattacharya S, et al. Leishmania donovani: effect of therapy on expression of CD2 antigen and secretion of macrophage migration inhibition factor by T-cells in patients with visceral leishmaniasis. Exp Parasitol. 2005;111:130-2 pubmed
    ..The study, therefore, identifies a possible role of CD2 antigen in immunity to VL. ..
  48. Schramm C, Huber S, Protschka M, Czochra P, Burg J, Schmitt E, et al. TGFbeta regulates the CD4+CD25+ T-cell pool and the expression of Foxp3 in vivo. Int Immunol. 2004;16:1241-9 pubmed
    ..Therefore, our study provides in vivo evidence for a role of TGFbeta in the homeostasis of CD4+CD25+ T-cells. ..
  49. Svane I, Nikolajsen K, Hansen S, Kamby C, Nielsen D, Johnsen H. Impact of high-dose chemotherapy on antigen-specific T cell immunity in breast cancer patients. Application of new flow cytometric method. Bone Marrow Transplant. 2002;29:659-66 pubmed
    ..These data indicate that introduction of a preventive cancer vaccination in combination with intensive chemotherapy may be a realistic treatment option. ..
  50. Daibata M, Taguchi T, Nemoto Y, Saito T, Machida H, Imai S, et al. Epstein-Barr virus (EBV)-positive pyothorax-associated lymphoma (PAL): chromosomal integration of EBV in a novel CD2-positive PAL B-cell line. Br J Haematol. 2002;117:546-57 pubmed
    ..This cell line represents the first example of EBV integration in PAL and could enable the study of the potential role of integrated viral infection in the development of PAL as well as mechanism of the aberrant phenotype expression. ..
  51. da Silva A, Brickelmaier M, Majeau G, Li Z, Su L, Hsu Y, et al. Alefacept, an immunomodulatory recombinant LFA-3/IgG1 fusion protein, induces CD16 signaling and CD2/CD16-dependent apoptosis of CD2(+) cells. J Immunol. 2002;168:4462-71 pubmed
    ..Thus alefacept acts as an effector molecule, mediating cognate interactions to activate Fc gamma R(+) cells (e.g., NK cells) to induce apoptosis of sensitive CD2(+) target cells. ..
  52. Zaru R, Cameron T, Stern L, Müller S, Valitutti S. Cutting edge: TCR engagement and triggering in the absence of large-scale molecular segregation at the T cell-APC contact site. J Immunol. 2002;168:4287-91 pubmed
  53. van der Merwe P. A subtle role for CD2 in T cell antigen recognition. J Exp Med. 1999;190:1371-4 pubmed