NKG2-C type II integral membrane protein or NKG2C is a protein that in humans is encoded by the KLRC2gene.[3][4]. It is also known as or cluster of differentiation 159c (CD159c).
Function
Natural killer (NK) cells are lymphocytes that can mediate lysis of certain tumor cells and virus-infected cells without previous activation. They can also regulate specific humoral and cell-mediated immunity. NK cells preferentially express several calcium-dependent (C-type) lectins, which have been implicated in the regulation of NK cell function. The group, designated KLRC (NKG2) are expressed primarily in natural killer (NK) cells and encodes a family of transmembrane proteins characterized by a type II membrane orientation (extracellular C terminus) and the presence of a C-type lectin domain. The KLRC (NKG2) gene family is located within the NK complex, a region that contains several C-type lectin genes preferentially expressed on NK cells. KLRC2 alternative splice variants have been described but their full-length nature has not been determined.[4]
Interactions
KLRC2 has been shown to interact and form dimers with CD94.[5][6] The CD94/NKG2C heterodimer can bind to HLA-E[7][8] and this binding leads to NK cells activation.
During infection with human cytomegalovirus, peptides derived from the virus are presented on HLA-E and natural killer cells that express the CD94/NKG2C receptor can specifically recognise the virus peptides. This recognition leads to activation, expansion, and differentiation of adaptive NK cells.[9]
^"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^Plougastel B, Trowsdale J (Apr 1998). "Sequence analysis of a 62-kb region overlapping the human KLRC cluster of genes". Genomics. 49 (2): 193–9. doi:10.1006/geno.1997.5197. PMID9598306.
^Lazetic S, Chang C, Houchins JP, Lanier LL, Phillips JH (Dec 1996). "Human natural killer cell receptors involved in MHC class I recognition are disulfide-linked heterodimers of CD94 and NKG2 subunits". Journal of Immunology. 157 (11): 4741–5. PMID8943374.
^Ding Y, Sumitran S, Holgersson J (May 1999). "Direct binding of purified HLA class I antigens by soluble NKG2/CD94 C-type lectins from natural killer cells". Scandinavian Journal of Immunology. 49 (5): 459–65. doi:10.1046/j.1365-3083.1999.00566.x. PMID10320637.
^Braud VM, Allan DS, O'Callaghan CA, Söderström K, D'Andrea A, Ogg GS, Lazetic S, Young NT, Bell JI, Phillips JH, Lanier LL, McMichael AJ (Feb 1998). "HLA-E binds to natural killer cell receptors CD94/NKG2A, B and C.". Nature. 391 (6669): 795–9. doi:10.1038/35869. PMID9486650.
^Hammer Q, Rückert T, Borst EM, Dunst J, Haubner A, Durek P, Heinrich F, Gasparoni G, Babic M, Tomic A, Pietra G, Nienen M, Blau IW, Hofmann J, Na IK, Prinz I, Koenecke C, Hemmati P, Babel N, Arnold R, Walter J, Thurley K, Mashreghi MF, Messerle M, Romagnani C (May 2018). "Peptide-specific recognition of human cytomegalovirus strains controls adaptive natural killer cells". Nature Immunology. 19 (5): 453–463. doi:10.1038/s41590-018-0082-6. PMID29632329.
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Houchins JP, Lanier LL, Niemi EC, Phillips JH, Ryan JC (Apr 1997). "Natural killer cell cytolytic activity is inhibited by NKG2-A and activated by NKG2-C". Journal of Immunology. 158 (8): 3603–9. PMID9103421.
Braud VM, Allan DS, O'Callaghan CA, Söderström K, D'Andrea A, Ogg GS, Lazetic S, Young NT, Bell JI, Phillips JH, Lanier LL, McMichael AJ (Feb 1998). "HLA-E binds to natural killer cell receptors CD94/NKG2A, B and C". Nature. 391 (6669): 795–9. doi:10.1038/35869. PMID9486650.
Lanier LL, Corliss B, Wu J, Phillips JH (Jun 1998). "Association of DAP12 with activating CD94/NKG2C NK cell receptors". Immunity. 8 (6): 693–701. doi:10.1016/S1074-7613(00)80574-9. PMID9655483.
Glienke J, Sobanov Y, Brostjan C, Steffens C, Nguyen C, Lehrach H, Hofer E, Francis F (Aug 1998). "The genomic organization of NKG2C, E, F, and D receptor genes in the human natural killer gene complex". Immunogenetics. 48 (3): 163–73. doi:10.1007/s002510050420. PMID9683661.
Ding Y, Sumitran S, Holgersson J (May 1999). "Direct binding of purified HLA class I antigens by soluble NKG2/CD94 C-type lectins from natural killer cells". Scandinavian Journal of Immunology. 49 (5): 459–65. doi:10.1046/j.1365-3083.1999.00566.x. PMID10320637.
Khakoo SI, Rajalingam R, Shum BP, Weidenbach K, Flodin L, Muir DG, Canavez F, Cooper SL, Valiante NM, Lanier LL, Parham P (Jun 2000). "Rapid evolution of NK cell receptor systems demonstrated by comparison of chimpanzees and humans". Immunity. 12 (6): 687–98. doi:10.1016/S1074-7613(00)80219-8. PMID10894168.
Ortega C, Romero P, Palma A, Orta T, Peña J, García-Vinuesa A, Molina IJ, Santamaría M (Dec 2004). "Role for NKG2-A and NKG2-C surface receptors in chronic CD4+ T-cell responses". Immunology and Cell Biology. 82 (6): 587–95. doi:10.1111/j.0818-9641.2004.01284.x. PMID15550116.
Gumá M, Busch LK, Salazar-Fontana LI, Bellosillo B, Morte C, García P, López-Botet M (Jul 2005). "The CD94/NKG2C killer lectin-like receptor constitutes an alternative activation pathway for a subset of CD8+ T cells". European Journal of Immunology. 35 (7): 2071–80. doi:10.1002/eji.200425843. PMID15940674.