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NKG2-C type II integral membrane protein is a protein that in humans is encoded by the KLRC2 gene.[1][2]


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.[2]


KLRC2 has been shown to interact with KLRD1.[3][4] The binding of this CD94/NKG2C heterodimer to its cellular ligand HLA-E has been shown to drive the expansion of a subset of Natural Killer (NK) cells in response to viral infections.[5]

See also


  1. 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. PMID 9598306.
  2. 2.0 2.1 "Entrez Gene: KLRC2 killer cell lectin-like receptor subfamily C, member 2".
  3. 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. PMID 8943374.
  4. 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. PMID 10320637.
  5. Rölle A, Pollmann J, Ewen EM, Le VT, Halenius A, Hengel H, Cerwenka A (Dec 2014). "IL-12-producing monocytes and HLA-E control HCMV-driven NKG2C+ NK cell expansion". The Journal of Clinical Investigation. 124 (12): 5305–16. doi:10.1172/JCI77440. PMC 4348979. PMID 25384219.

Further reading

  • Houchins JP, Yabe T, McSherry C, Bach FH (Apr 1991). "DNA sequence analysis of NKG2, a family of related cDNA clones encoding type II integral membrane proteins on human natural killer cells". The Journal of Experimental Medicine. 173 (4): 1017–20. doi:10.1084/jem.173.4.1017. PMC 2190798. PMID 2007850.
  • Yabe T, McSherry C, Bach FH, Fisch P, Schall RP, Sondel PM, Houchins JP (1993). "A multigene family on human chromosome 12 encodes natural killer-cell lectins". Immunogenetics. 37 (6): 455–60. doi:10.1007/BF00222470. PMID 8436421.
  • 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. PMID 9103421.
  • 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. PMID 9486650.
  • 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. PMID 9655483.
  • 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. PMID 9683661.
  • 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. PMID 10320637.
  • 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. PMID 10894168.
  • Shum BP, Flodin LR, Muir DG, Rajalingam R, Khakoo SI, Cleland S, Guethlein LA, Uhrberg M, Parham P (Jan 2002). "Conservation and variation in human and common chimpanzee CD94 and NKG2 genes". Journal of Immunology. 168 (1): 240–52. doi:10.4049/jimmunol.168.1.240. PMID 11751968.
  • Hikami K, Tsuchiya N, Yabe T, Tokunaga K (Mar 2003). "Variations of human killer cell lectin-like receptors: common occurrence of NKG2-C deletion in the general population". Genes and Immunity. 4 (2): 160–7. doi:10.1038/sj.gene.6363940. PMID 12618865.
  • Miyashita R, Tsuchiya N, Hikami K, Kuroki K, Fukazawa T, Bijl M, Kallenberg CG, Hashimoto H, Yabe T, Tokunaga K (Jan 2004). "Molecular genetic analyses of human NKG2C (KLRC2) gene deletion". International Immunology. 16 (1): 163–8. doi:10.1093/intimm/dxh013. PMID 14688071.
  • 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. PMID 15550116.
  • 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. PMID 15940674.

This article incorporates text from the United States National Library of Medicine, which is in the public domain.