FUNCTION OF KILLER-CELL INHIBITORY RECEPTORS FOR MHC CLASS-I MOLECULES

NK- and T-cells express at their surface, members of a multigenic fami ly of killer-cell inhibitory receptors (KIR) for MHC Class I molecules . KIR engagement leads to the inhibition of NK- and T-cell activation programs. These receptors recruit the protein tyrosine phosphatases (P TPase), SHP-1 and SHP-2, upon tyrosine phosphorylation of immunorecept or tyrosine-based inhibition motif (ITIM) expressed in both human and mouse KIR. We further define the ITIM amino acids sequence required in that recognition and demonstrate the critical role of the phospho Y-2 amino acid residue in this V/IxYxxL/V motif. In addition, using RBL-2 H3 cells expressing endogenous Fc epsilon RI receptors as well as tran sfected CD25/CD3 zeta chimera and p58.183 human KIR, we show that KIR inhibitory function requires co-engagement of KIR and ITAM-containing receptors. These results document the pathway used by KIR to down-regu late NK- and T-cell activation programs. (C) 1996 Elsevier Science B.V .