The functions of natural killer (NK) cells are controlled by an abundance of activating and inhibitory receptors. Many of these interact with MHC class I molecules. The MHC system also interacts with cytotoxic T-lymphocytes and has been shown to comprise a rapidly evolving family of molecules. This challenges the functional relationship of NK cell receptors with their ligands. Although individual receptors have become subject to species-specific expansions over evolutionary time, the main themes of the NK cell interaction with MHC class I have been preserved. This review details the interaction of NK cell receptors with MHC class I and discusses their unexpectedly rapid evolution.

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