SIGNAL-TRANSDUCTION BY HUMAN NK CELL MHC-RECOGNIZING RECEPTORS

Cells may be protected from natural killer (NK)-cell-mediated killing by the expression of specific MHC class I complexes. This protective e ffect is due to the expression on NK cells of MHC class I-recognizing receptors which, upon ligation, transduce potent inhibitory signals in to the NK cells. The molecular signalling mechanisms employed by the h uman NK-cell MHC-recognizing killer cell inhibitory receptors (HR) and CD94 are the focus of this review. A sequential model of KIR signalli ng involving lck-dependent tyrosine phosphorylation of KIR and subsequ ent association of KIR with the SH2-containing tyrosine phosphatase, S HP-1, is presented. We explore how engagement of either KIR or CD94 mo dulates the protein tyrosine kinase-dependent biochemical signals resp onsible for activation of NK-cell cytotoxic function. Additionally, we discuss models of inhibitory signalling proposed for each of the lymp hocyte lineages, emphasizing that disparate molecular mechanisms may b e utilized by cells to produce similar biological responses.