The natural killer gene complex encodes proteins, some of which are structurally unrelated, that impact on NK-cell function. Detailed analyses have indicated that these molecules are involved in NK-cell recognition, activation, and inhibition. The importance of this genomic region is highlighted by studies indicating that NKC-associated genes significantly influence NK cell-mediated innate host defense against life-threatening pathogens and that the NKC is conserved among diverse species. Thus, further elucidation of the NKC and its gene products will provide a genetic basis for understanding innate immunity and NK-cell activity at the molecular level.
Natural killer (NK) cells express C-type lectinlike receptors, encoded in the NK gene complex, that interact with major histocompatibility complex class I and either inhibit or activate functional activity. Human NK cells express heterodimers consisting of CD94 and NKG2 family molecules, whereas murine NK cells express homodimers belonging to the Ly-49 family. The corresponding orthologues for other species, however, have not been described. In this report, we used probes derived from the expressed sequence tag database to clone C57BL͞6-derived cDNAs homologous to human NKG2-D and CD94. Among normal tissues, murine NKG2-D and CD94 transcripts are highly expressed only in activated NK cells, including both Ly-49A ؉ and Ly-49A ؊ subpopulations. Additionally, mNKG2-D is expressed in murine NK cell clones KY-1 and KY-2, whereas mCD94 expression is observed only in KY-1 cells but not KY-2. Last, we have finely mapped the physical location of the Cd94 (centromeric) and Nkg2d (telomeric) genes between Cd69 and the Ly49 cluster in the NK complex. Thus, these data indicate the expanding complexity of the NK complex and the corresponding repertoire of C-type lectin-like receptors on murine NK cells.Natural killer (NK) cells are a distinct lymphocytic lineage that functions as a critical component of innate immunity against a wide variety of intracellular and parasitic pathogens and may also mediate tumor surveillance and influence hematopoiesis (1, 2). The activity of NK cells is controlled by inhibitory surface receptors for major histocompatibility complex (MHC) class I molecules (3, 4). Two structural types of NK receptors for MHC class I have been described-type I integral membrane Ig-like killer inhibitory receptors and type II integral-membrane C type lectin-like disulfide-linked dimers, including the human (h) CD94͞NKG2 family of heterodimers and the murine (m) Ly-49 family of homodimers (5-8). Both types of NK cell receptors for MHC class I transmit potent inhibitory signals that are dependent upon the presence of immunoreceptor tyrosine-based inhibitory motifs (ITIM) consisting of the consensus sequence I͞VXYXXV͞L in the cytoplasmic domains (9, 10). Receptor cross-linking appears to lead to tyrosine phosphorylation of the ITIM and the subsequent recruitment of the SHP-1 intracellular tyrosine phosphatase that then presumably dephosphorylates tyrosine residues on molecules involved in the activation cascade.Among the C-type lectin-like receptors, cross-linking of hCD94 with a mAb either inhibited cytolytic activity or induced redirected lysis of various NK clones, leading to confusion about its function in NK cells (11)(12)(13)(14). Remarkably, the cDNA sequence of CD94 reveals an extremely short cytoplasmic domain that contains no consensus sequences involved in cell signaling (15). The phenotypic differences observed with CD94 engagement has been recently clarified in studies demonstrating that CD94 forms heterodimers with NKG2 molecules (16,17). At least five NKG2 family members have been described in h...
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.