The NKC and regulation of natural killer cell-mediated immunity

Abstract

The natural killer gene complex (NKC) contains many linked genes that encode type II protein members of the C-type lectin superfamily. Most of these genes are discretely clustered in families within the gene complex. NKC gene order and organization is conserved among humans and rodents suggesting common ancestry and conservation of function. Most known NKC encoded mole­cules are expressed at the plasma membrane of natural killer cells as disulfide-linked, dimeric receptors that may either activate or inhibit NK cell activity, de­pendent upon the presence or absence of cytoplasmic domain regulatory sequences. In addition, both classical and non-classical MHC molecules may modulate natural killing through engagement of these receptors. Notably, several NKC loci control various immunologic phenotypes, including the Cmvl locus that regulates NK cell-mediated immunity to murine cytomegalovirus. As a means to understand NKC regulation of viral immunity, we have cloned and mapped the NKC. Moreover, by genetic analysis of intra-NKC recombinant mice we have physically defined a Cmvl critical region (<300 kb) between the NKC-linked Ly49 and Prp gene clusters. Thus, this detailed evaluation of the NKC will lead to enhanced understanding of the role of NK cells in innate immunity.