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 cells are known since several years: they are represented by different families of MHC-specific receptors characterized by ITIM sequences in their cytoplasmic tail. In contrast, the surface molecules responsible for NK cell activation in the process of natural cytotoxicity and tumor cell lysis have remained elusive until recently. Three distinct NK-specific molecules termed 'natural cytotoxicity receptors' (NCR) have recently been identified and cloned. They play a complementary role in mediating NK cell activation in the interaction and lysis of most tumor cells. They are associated with different ITAM-containing adaptor proteins mediating signal transduction. Molecular cloning revealed novel members of the Ig superfamily displaying a limited homology with known human receptors.