Natural Killer Cell Education and Tolerance

Natural killer (NK) cells play a key role in the immune response to certain infections and malignancies by direct cytolysis of infected or transformed cells and by secretion of potent immune mediators. NK cells express an array of activating receptors that recognize self-molecules. If not restrained by inhibitory receptors recognizing major histocompatibility complex (MHC) class I proteins on the surface of self cells, NK cells are able to kill normal, healthy cells. Not all NK cells express inhibitory receptors for self-MHC class I; thus, other tolerance mechanisms are necessary to prevent NK cell-mediated autoimmunity. Here we review the major mechanisms of NK cell education and tolerance