Surface receptors delivering opposite signals regulate the function of human NK cells

The effector function of NK cells is regulated by a number of positive and negative signals. The receptors involved in the negative regulation of NK c ells are Known since several years: they ave represented by different famil ies of MHC-specific receptors characterized by ITIM sequences in their cyto plasmic tail. In contrast, the surface molecules responsible for NK cell ac tivation in the process of natural cytotoxicity and tumor cell lysis have r emained elusive until recently. Three distinct NK-specific molecules termed 'natural cytotoxicity receptors' (NCR) have recently been identified and c loned They play a complementary role in mediating NK cell activation in the interaction and lysis of most tumor cells. They are associated with differ ent ITAM-containing adaptor proteins mediating signal transduction. Molecul ar cloning revealed novel members of the Ig superfamily displaying a limite d homology with known human receptors.