The cytoplasmic tail of killer inhibitory receptor (KIR) associates with TCR zeta in a phosphorylation-dependent manner

Killer inhibitory receptor (KIR) inhibits cytolytic function of killer cell s by specific interaction with class I MHC molecules. The inhibitory effect mediated by KIR requires co-engagement of KIR with an activating receptor, such as TCR or FcR. This implies that KIR may function in the immediate vi cinity of activating molecules, and previous studies have shown that p58 KI R is associated with TCR zeta- and FcR gamma-chain in NK cells. To better u nderstand the molecular interaction between KIR and TCR zeta-chain, we gene rated a His-tag fusion protein of a p70 KIR cytoplasmic tail (His-CytKIR) a nd used this protein to coprecipitate TCR zeta-chain from Jurkat T cells. W estern blots of the resolved coprecipitates showed that the cytoplasmic tai l of KIR associates with TCR zeta in vitro. Interestingly, the association between the His-CytKTR and TCR zeta was dependent on the phosphorylation of the His-CytKIR. Unlike the unphosphorylated His-CytKIR, the phosphorylated form no longer associated with TCR zeta. However, the association was not affected by the tyrosine phosphorylation of TCR zeta. These results suggest that the cytoplasmic tail of KIR may couple to TCR zeta in a phosphorylati on-dependent manner, so it could fine-tune the activation signals induced v ia the TCR. (C) 1999 Elsevier Science B.V. All rights reserved.