Alternative titles; symbols
HGNC Approved Gene Symbol: KLRB1
Cytogenetic location: 12p13.31 Genomic coordinates (GRCh38): 12:9,594,551-9,607,916 (from NCBI)
Natural killer (NK) cells are lymphocytes that mediate cytotoxicity and secrete cytokines after immune stimulation. Several genes of the C-type lectin superfamily, including the rodent NKRP1 family of glycoproteins, are expressed by NK cells and may be involved in the regulation of NK cell function. Using an expression cloning strategy, Lanier et al. (1994) identified an IL2-activated polyclonal NK cell line cDNA encoding a human NKRP1 homolog that they designated NKRP1A. The predicted protein contains a 158-amino acid extracellular domain with several motifs characteristic of C-type lectins, a 29-amino acid transmembrane domain, and a 38-amino acid cytoplasmic domain. NKRP1A is classified as a type II membrane protein because it has an external C terminus. The amino acid sequence of NKRP1A is 46% identical to those of rat and mouse NKRP1, and 26% identical to human NKG2A. On Northern blots of an IL2-activated polyclonal NK cell line, Lanier et al. (1994) observed a single broad 0.8- to 1.3-kb signal. Using flow cytometry, they found that NKRP1 is present on a subset of human NK cells and on approximately 25% of peripheral blood T cells.
Aldemir et al. (2005) found that LLT1 (CLEC2D; 605659) bound to cells expressing CD161. Expression of LLT1 in various NK-cell targets rapidly reduced CD161 surface expression, protected the targets from NK-mediated lysis, and inhibited IFNG (147570) production. Anti-CD161 alone failed to stimulate T-cell secretion of IFNG, but anti-CD161 together with anti-CD3 (see 186740) enhanced IFNG production compared with anti-CD3 alone. Aldemir et al. (2005) concluded that LLT1 is a ligand for CD161 and that their interaction differentially regulates NK- and T-cell functions. Rosen et al. (2005) presented similar findings.
Kleinschek et al. (2009) demonstrated that CD161-positive CD4 (186940) T cells comprise a circulating and gut-resident Th17 cell (see IL17A; 603149) population. During Crohn disease (CD; 266600), these cells displayed increased expression of IL17, IL22 (605330), and IL23R (607562). CD161-positive CD4 cells from CD patients produced both IL17 and IFNG upon stimulation with IL23 (605580), whereas cells from healthy subjects first required priming by inflammatory stimuli. CD161-positive Th17 cells appeared to be imprinted for gut homing, as indicated by high expression of CCR6 (601835) and ITGB7 (147559), and were found in increased numbers in inflammatory cells in CD lesions. Kleinschek et al. (2009) concluded that CD161-positive CD4 T cells are a resting pool of Th17 cells that can be activated by IL23 and mediate destructive tissue inflammation.
Lanier et al. (1994) mapped the NKRP1A gene to chromosome 12 using a somatic cell hybrid panel. By fluorescence in situ hybridization and analysis of a YAC contig, Renedo et al. (1997) found that NKRP1A, or NKR, is the most distal gene in an NK gene complex (NKC) located at 12p13-p12. The NKC contains several C-type lectin genes preferentially expressed in NK cells, including CD69 (107273), members of the NKG2 family, and CD94 (KLRD1; 602894).
Aldemir, H., Prod'homme, V., Dumaurier, M.-J., Retiere, C., Poupon, G., Cazareth, J., Bihl, F., Braud, V. M. Cutting edge: lectin-like transcript 1 is a ligand for the CD161 receptor. J. Immun. 176: 7791-7795, 2005.
Kleinschek, M. A., Boniface, K., Sadekova, S., Grein, J., Murphy, E. E., Turner, S. P., Raskin, L., Desai, B., Faubion, W. A., de Waal Malefyt, R., Pierce, R. H., McClanahan, T., Kastelein, R. A. Circulating and gut-resident human Th17 cells express CD161 and promote intestinal inflammation. J. Exp. Med. 206: 525-534, 2009. [PubMed: 19273624] [Full Text: https://doi.org/10.1084/jem.20081712]
Lanier, L. L., Chang, C., Phillips, J. H. A disulfide-linked homodimer of the C-type lectin superfamily expressed by a subset of NK and T lymphocytes. J. Immun. 153: 2417-2428, 1994. [PubMed: 8077657]
Renedo, M., Arce, I., Rodriguez, A., Carretero, M., Lanier, L. L., Lopez-Botet, M., Fernandez-Ruiz, E. The human natural killer gene complex is located on chromosome 12p12-p13. Immunogenetics 46: 307-311, 1997. [PubMed: 9218532] [Full Text: https://doi.org/10.1007/s002510050276]
Rosen, D. B., Bettadapura, J., Alsharifi, M., Mathew, P. A., Warren, H. S., Lanier, L. L. Cutting edge: lectin-like transcript-1 is a ligand for the inhibitory human NKR-P1A receptor. J. Immun. 176: 7796-7799, 2005.