Receptors on NK cells

This chapter reviews the known NK receptors, their function, ligand specificity, and their overall contribution to NK cell recognition. Natural killer (NK) cells are bone marrow derived lymphocytes that are well-equipped for the destruction of tumor and virally infected cells without the need for prior antigen stimulation. Their killing machinery is quite complex and is determined by integrated signals obtained from activating and inhibitory receptors. Inhibitory receptors recognize molecules that are expressed on normal cells as a means of protecting healthy cells from attack by NK. This complex repertoire of NK cell receptors results in various NK cell subpopulations that can respond to bacteria, viruses, parasites, and tumor. Thus, although NK cells (unlike T and B cells) express only a limited number of receptors, the various combinations of receptors enable a remarkable diversity in NK cell activity. The prototypic inhibitory receptors recognize MHC class I molecules, but recent work has identified inhibitory receptors that have non-MHC-molecule ligands. The NK-activating receptors recognize pathogen-derived, stress-induced molecules and a series of still uncharacterized cellular ligands. Some of the future challenges in the NK field might include population dynamics, elucidating the precise threshold needed for NK cell activation and inhibition, and identifying the entire spectrum of NK cell inhibitory and activating receptors followed by the identification of their various physiological ligands.