Early signaling via inhibitory and activating NK receptors

This review focuses on recent findings on the structural features of inhibitory NK cell receptors containing immunoreceptor tyrosine-based inhibition motif (ITIM) and of NK cell activating receptors, both in human and mouse. First, the study of the inhibitory killer cell immunoglobulin-like receptors (KIR) unveiled the presence of intracytoplasmic ITIM and their capacity to recruit protein tyrosine phosphatases such as SHP-1 in vivo. A brief summary of the known SHP-1 targets may help us to understand the inhibition mediated by the KIR. The characterization of ITIM thus allowed the definition of a large group of inhibitory cell surface receptors. The second part of the review describes the known NK cell activating receptors. Most of them require association with ITAM-containing polypeptides in order to mediate cell activation.