Encyclopedia of Signaling Molecules

2018 Edition
| Editors: Sangdun Choi


Reference work entry
DOI: https://doi.org/10.1007/978-3-319-67199-4_101856


Historical Background

The T cell surface glycoprotein CD6 was first identified in 1981 by Kamoun et al. who for that purpose used a monoclonal antibody 12.1, raised against a human secondary mixed leukocyte reaction, that labeled all normal T cells and many T- and B-cell leukemias and lymphomas (Kamoun et al. 1981). The CD6 gene was later cloned from HPB-ALL cells by the group of Brian Seed using his pioneering cloning strategy, and revealed sequences with high homology with the cysteine-rich domain of the type I scavenger receptor of macrophages (Aruffo et al. 1991). Nevertheless, the obtained cDNA was incomplete such that the sequence corresponding to the cytoplasmic tail only coded for 44 amino acids. Based on comparisons with the mouse CD6 gene, Jane Parnes and colleagues finally published the currently known sequence, which includes a cytoplasmic tail of 244 amino acids (Robinson et al. 1995).

CD6 is highly...

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  1. Aruffo A, Melnick MB, Linsley PS, Seed B. The lymphocyte glycoprotein CD6 contains a repeated domain structure characteristic of a new family of cell surface and secreted proteins. J Exp Med. 1991;174(4):949–52.PubMedCrossRefGoogle Scholar
  2. Bonet L, Farnós M, Martínez-Florensa M, Martínez VG, Lozano F. Identification of functionally relevant phoshorylatable serine clusters in the cytoplasmic region of the human CD6 lymphocyte surface receptor. FEBS Lett. 2013;587(14):2205–13.PubMedCrossRefGoogle Scholar
  3. Castro MAA, Nunes RJ, Oliveira MI, Tavares PA, Simões C, Parnes JR, et al. OX52 is the rat homologue of CD6: evidence for an effector function in the regulation of CD5 phosphorylation. J Leukoc Biol. 2003;73(1):183–90.PubMedCrossRefGoogle Scholar
  4. De Jager PL, Jia X, Wang J, de Bakker PI, Ottoboni L, Aggarwal NT, et al. Meta-analysis of genome scans and replication identify CD6, IRF8 and TNFRSF1A as new multiple sclerosis susceptibility loci. Nat Genet. 2009;41(7):776–82.PubMedPubMedCentralCrossRefGoogle Scholar
  5. Gimferrer I, Calvo M, Mittelbrunn M, Farnós M, Sarrias MR, Enrich C, et al. Relevance of CD6-mediated interactions in T cell activation and proliferation. J Immunol. 2004;173(4):2262–70.PubMedCrossRefGoogle Scholar
  6. Gimferrer I, Ibáñez A, Farnós M, Sarrias MR, Fenutría R, Roselló S, et al. The lymphocyte receptor CD6 interacts with syntenin-1, a scaffolding protein containing PDZ domains. J Immunol. 2005;175(3):1406–14.PubMedCrossRefGoogle Scholar
  7. Hassan NJ, Barclay AN, Brown MH. Optimal T cell activation requires the engagement of CD6 and CD166. Eur J Immunol. 2004;34(4):930–40.PubMedCrossRefGoogle Scholar
  8. Hassan NJ, Simmonds SJ, Clarkson NG, Hanrahan S, Puklavec MJ, Bomb M, et al. CD6 regulates T-cell responses through activation-dependent recruitment of the positive regulator SLP-76. Mol Cell Biol. 2006;26(17):6727–38.PubMedPubMedCentralCrossRefGoogle Scholar
  9. Kamoun M, Kadin ME, Martin PJ, Nettleton J, Hansen JA A novel human T cell antigen preferentially expressed on mature T cells and shared by both well and poorly differentiated B cell leukemias and lymphomas. J Immunol. 1981;127(3):987–91.PubMedGoogle Scholar
  10. Kofler DM, Severson CA, Mousissian N, De Jager PL, Hafler DA. The CD6 multiple sclerosis susceptibility allele is associated with alterations in CD4+ T cell proliferation. J Immunol. 2011;187(6):3286–91.PubMedCrossRefGoogle Scholar
  11. Ledbetter JA, Norris NA, Grossmann A, Grosmaire LS, June CH, Uckun FM, et al. Enhanced transmembrane signalling activity of monoclonal antibody heteroconjugates suggests molecular interactions between receptors on the T cell surface. Mol Immunol. 1989;26(2):137–45.PubMedCrossRefGoogle Scholar
  12. Nair P, Melarkode R, Rajkumar D, Montero E. CD6 synergistic co-stimulation promoting proinflammatory response is modulated without interfering with the activated leucocyte cell adhesion molecule interaction. Clin Exp Immunol. 2010;162(1):116–30.PubMedPubMedCentralCrossRefGoogle Scholar
  13. Oliveira MI, Gonçalves CM, Pinto M, Fabre S, Santos AM, Lee SF, et al. CD6 attenuates early and late signaling events, setting thresholds for T-cell activation. Eur J Immunol. 2012;42(1):195–205.PubMedCrossRefGoogle Scholar
  14. Orta-Mascaró M, Consuegra-Fernández M, Carreras E, Roncagalli R, Carreras-Sureda A, Alvarez P, et al. CD6 modulates thymocyte selection and peripheral T cell homeostasis. J Exp Med. 2016;213(8):1387–97.PubMedPubMedCentralCrossRefGoogle Scholar
  15. Pinto M, Carmo AM. CD6 as a therapeutic target in autoimmune diseases: successes and challenges. BioDrugs. 2013;27(3):191–202.PubMedCrossRefGoogle Scholar
  16. Reinherz EL, Geha R, Rappeport JM, Wilson M, Penta AC, Hussey RE, et al. Reconstitution after transplantation with T-lymphocyte-depleted HLA haplotype-mismatched bone marrow for severe combined immunodeficiency. Proc Natl Acad Sci USA. 1982;79(19):6047–51.PubMedPubMedCentralCrossRefGoogle Scholar
  17. Robinson WH, Neuman de Vegvar HE, Prohaska SS, Rhee JW, Parnes JR. Human CD6 possesses a large, alternatively spliced cytoplasmic domain. Eur J Immunol. 1995;25(10):2765–9.PubMedCrossRefGoogle Scholar
  18. Roncagalli R, Hauri S, Fiore F, Liang Y, Chen Z, Sansoni A, et al. Quantitative proteomics analysis of signalosome dynamics in primary T cells identifies the surface receptor CD6 as a Lat adaptor-independent TCR signaling hub. Nat Immunol. 2014;15(4):384–92.PubMedPubMedCentralCrossRefGoogle Scholar
  19. Santos RF, Oliveira L, Carmo AM. Tuning T cell activation: the function of CD6 at the immunological synapse and in T cell responses. Curr Drug Targets. 2016;17(6):630–9.PubMedCrossRefGoogle Scholar
  20. Walker C, Bettens F, Pichler WJ. T cell activation by cross-linking anti-CD3 antibodies with second anti-T cell antibodies: dual antibody cross-linking mimics physical monocyte interaction. Eur J Immunol. 1987;17(11):1611–8.PubMedCrossRefGoogle Scholar

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© Springer International Publishing AG 2018

Authors and Affiliations

  1. 1.i3S - Instituto de Investigação e Inovação em SaúdeUniversidade do PortoPortoPortugal
  2. 2.IBMC – Instituto de Biologia Molecular e CelularPortoPortugal
  3. 3.ICBAS – Instituto de Ciências Biomédicas Abel SalazarUniversidade do PortoPortoPortugal