Natural killer (NK) cells, like B and T lymphocytes, are potent effector cells that are crucial for immunity to tumors and infections. These effector responses must be controlled to avoid inadvertent attack against normal self. Yet, the mechanisms that guide NK cell tolerance differ from those guiding T and B cell tolerance. Here, we discuss how NK cells are licensed by self-MHC class I molecules through their inhibitory receptors which results in NK cell functional competence to be triggered through their activation receptors. We discuss recent data with respect to issues related to licensing, thereby providing a framework for unifying concepts on NK cell education.
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