6ng3

Structural highlights

Function

[BY55_HUMAN] CD160 antigen: Receptor on immune cells capable to deliver stimulatory or inhibitory signals that regulate cell activation and differentiation. Exists as a GPI-anchored and as a transmembrane form, each likely initiating distinct signaling pathways via phosphoinositol 3-kinase in activated NK cells and via LCK and CD247/CD3 zeta chain in activated T cells (PubMed:19109136, PubMed:11978774, PubMed:17307798). Receptor for both classical and non-classical MHC class I molecules (PubMed:9973372, PubMed:12486241). In the context of acute viral infection, recognizes HLA-C and triggers NK cell cytotoxic activity, likely playing a role in anti-viral innate immune response (PubMed:12486241). On CD8+ T cells, binds HLA-A2-B2M in complex with a viral peptide and provides a costimulatory signal to activated/memory T cells (PubMed:9973372). Upon persistent antigen stimulation, such as occurs during chronic viral infection, may progressively inhibit TCR signaling in memory CD8+ T cells, contributing to T cell exhaustion (PubMed:25255144). On endothelial cells, recognizes HLA-G and controls angiogenesis in immune privileged sites (PubMed:16809620). Receptor or ligand for TNF superfamily member TNFRSF14, participating in bidirectional cell-cell contact signaling between antigen presenting cells and lymphocytes. Upon ligation of TNFRSF14, provides stimulatory signal to NK cells enhancing IFNG production and anti-tumor immune response (By similarity). On activated CD4+ T cells, interacts with TNFRSF14 and downregulates CD28 costimulatory signaling, restricting memory and alloantigen-specific immune response (PubMed:18193050). In the context of bacterial infection, acts as a ligand for TNFRSF14 on epithelial cells, triggering the production of antimicrobial proteins and proinflammatory cytokines (By similarity).[UniProtKB:O88875]^{[1] [2] [3] [4] [5] [6] [7] [8]} CD160 antigen, soluble form: The soluble GPI-cleaved form, usually released by activated lymphocytes, might play an immune regulatory role by limiting lymphocyte effector functions.^[9]

References

1. ↑ Nikolova M, Marie-Cardine A, Boumsell L, Bensussan A. BY55/CD160 acts as a co-receptor in TCR signal transduction of a human circulating cytotoxic effector T lymphocyte subset lacking CD28 expression. Int Immunol. 2002 May;14(5):445-51. doi: 10.1093/intimm/14.5.445. PMID:11978774 doi:http://dx.doi.org/10.1093/intimm/14.5.445
2. ↑ Le Bouteiller P, Barakonyi A, Giustiniani J, Lenfant F, Marie-Cardine A, Aguerre-Girr M, Rabot M, Hilgert I, Mami-Chouaib F, Tabiasco J, Boumsell L, Bensussan A. Engagement of CD160 receptor by HLA-C is a triggering mechanism used by circulating natural killer (NK) cells to mediate cytotoxicity. Proc Natl Acad Sci U S A. 2002 Dec 24;99(26):16963-8. doi:, 10.1073/pnas.012681099. Epub 2002 Dec 16. PMID:12486241 doi:http://dx.doi.org/10.1073/pnas.012681099
3. ↑ Fons P, Chabot S, Cartwright JE, Lenfant F, L'Faqihi F, Giustiniani J, Herault JP, Gueguen G, Bono F, Savi P, Aguerre-Girr M, Fournel S, Malecaze F, Bensussan A, Plouet J, Le Bouteiller P. Soluble HLA-G1 inhibits angiogenesis through an apoptotic pathway and by direct binding to CD160 receptor expressed by endothelial cells. Blood. 2006 Oct 15;108(8):2608-15. doi: 10.1182/blood-2005-12-019919. Epub 2006, Jun 29. PMID:16809620 doi:http://dx.doi.org/10.1182/blood-2005-12-019919
4. ↑ Rabot M, El Costa H, Polgar B, Marie-Cardine A, Aguerre-Girr M, Barakonyi A, Valitutti S, Bensussan A, Le Bouteiller P. CD160-activating NK cell effector functions depend on the phosphatidylinositol 3-kinase recruitment. Int Immunol. 2007 Apr;19(4):401-9. doi: 10.1093/intimm/dxm005. Epub 2007 Feb 16. PMID:17307798 doi:http://dx.doi.org/10.1093/intimm/dxm005
5. ↑ Cai G, Anumanthan A, Brown JA, Greenfield EA, Zhu B, Freeman GJ. CD160 inhibits activation of human CD4+ T cells through interaction with herpesvirus entry mediator. Nat Immunol. 2008 Feb;9(2):176-85. doi: 10.1038/ni1554. Epub 2008 Jan 13. PMID:18193050 doi:http://dx.doi.org/10.1038/ni1554
6. ↑ Giustiniani J, Bensussan A, Marie-Cardine A. Identification and characterization of a transmembrane isoform of CD160 (CD160-TM), a unique activating receptor selectively expressed upon human NK cell activation. J Immunol. 2009 Jan 1;182(1):63-71. doi: 10.4049/jimmunol.182.1.63. PMID:19109136 doi:http://dx.doi.org/10.4049/jimmunol.182.1.63
7. ↑ Vigano S, Banga R, Bellanger F, Pellaton C, Farina A, Comte D, Harari A, Perreau M. CD160-associated CD8 T-cell functional impairment is independent of PD-1 expression. PLoS Pathog. 2014 Sep 25;10(9):e1004380. doi: 10.1371/journal.ppat.1004380., eCollection 2014 Sep. PMID:25255144 doi:http://dx.doi.org/10.1371/journal.ppat.1004380
8. ↑ Agrawal S, Marquet J, Freeman GJ, Tawab A, Bouteiller PL, Roth P, Bolton W, Ogg G, Boumsell L, Bensussan A. Cutting edge: MHC class I triggering by a novel cell surface ligand costimulates proliferation of activated human T cells. J Immunol. 1999 Feb 1;162(3):1223-6. PMID:9973372
9. ↑ Giustiniani J, Marie-Cardine A, Bensussan A. A soluble form of the MHC class I-specific CD160 receptor is released from human activated NK lymphocytes and inhibits cell-mediated cytotoxicity. J Immunol. 2007 Feb 1;178(3):1293-300. doi: 10.4049/jimmunol.178.3.1293. PMID:17237375 doi:http://dx.doi.org/10.4049/jimmunol.178.3.1293