NK CELL RECEPTORS

NK cells are regulated by opposing signals from receptors that activat e and inhibit effector function. While positive stimulation may be ini tiated by an array of costimulatory receptors, specificity is provided by inhibitory signals transduced by receptors for MHC class I. Three distinct receptor families, Ly49, CD94/NKG2, and KIR, are involved in NK cell recognition of polymorphic MHC class I molecules. A common pat hway of inhibitory signaling is provided by ITIM sequences in the cyto plasmic domains of these otherwise structurally diverse receptors. Upo n ligand binding and activation, the inhibitory NK cell receptors beco me tyrosine phosphorylated and recruit tyrosine phosphatases, SHP-1 an d possibly SHP-2, resulting in inhibition of NK cell-mediated cytotoxi city and cytokine expression. Recent studies suggest these inhibitory NK cell receptors are members of a larger superfamily containing ITIM sequences, the inhibitory receptor superfamily (IRS).