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 effect is due to the expression on NK cells of MHC class I-recognizing receptors which, upon ligation, transduce potent inhibitory signals into the NK cells. The molecular signalling mechanisms employed by the human NK-cell MHC-recognizing killer cell inhibitory receptors (KIR) and CD94 are the focus of this review. A sequential model of KIR signalling involving lck-dependent tyrosine phosphorylation of KIR and subsequent association of KIR with the SH2-containing tyrosine phosphatase, SHP-1, is presented. We explore how engagement of either KIR or CD94 modulates the protein tyrosine kinase-dependent biochemical signals responsible for activation of NK-cell cytotoxic function. Additionally, we discuss models of inhibitory signalling proposed for each of the lymphocyte lineages, emphasizing that disparate molecular mechanisms may be utilized by cells to produce similar biological responses.