Conserved and variable natural killer cell receptors: diverse approaches to viral infections

Natural killer (NK) cells are lymphocytes of the innate immune system with essential roles during viral infections. NK cell functions are mediated through a repertoire of non-rearranging inhibitory and activating receptors that interact with major histocompatibility complex (MHC)–peptide complexes on the surface of infected cells. Recent work studying the conserved CD94–NKG2A and variable killer cell immunoglobulin-like receptor–MHC systems suggest that these two receptor families may have subtly different properties in terms of interactions with MHC class I bound peptides, and in recognition of down-regulation of MHC class I. In this review, we discuss how these properties generate diversity in the NK cell response to viruses.