Natural killer cell specificity for viral infections

Natural killer (NK) cells are lymphocytes that contribute to the early immune responses to viruses. NK cells are innate immune cells that do not express rearranged antigen receptors but sense their environment via receptors for pro-inflammatory cytokines, as well as via germline-encoded activating receptors specific for danger or pathogen signals. A group of such activating receptors is stochastically expressed by certain subsets within the NK cell compartment. After engagement of the cognate viral ligand, these receptors contribute to the specific activation and ‘preferential’ population expansion of defined NK cell subsets, which partially recapitulate some features of adaptive lymphocytes. In this Review, we discuss the numerous modes for the specific recognition of viral antigens and peptides by NK cells and the implications of this for the composition of the NK cell repertoire as well as for the the selection of viral variants. Romagnani and colleagues discuss the specific recognition of viral antigens and peptides by NK cells and its implications for the composition of the NK cell repertoire and the selection of viral variants.