Missing self recognition and self tolerance of natural killer (NK) cells

Natural killer cells express inhibitory receptors specific for polymorphic MHC molecules, which enables them to mediate “missing self recognition”, the capacity to attack self cells that extinguish expression of MHC class I molecules. A key question is: how are NK cells rendered self-tolerant? It was proposed that all NK cells express at least one inhibitory receptor specific for self MHC, but we recently identified an NK cell subset that does not. Instead, these NK cells, like anergic B and T cells, are hyporesponsive to stimulation. These findings indicate that NK cell activity can be modulated independently of inhibitory receptors specific for MHC molecules, and that such modulation may contribute to self tolerance. This review summarizes current understanding of NK cell recognition and self tolerance.