[Regulatory mechanisms of NK cell functions]

Natural Killer (NK) cells discriminate self from non-self in a manner distinct from T cells. NK cells exhibit cytotoxicity against "missing-self" by killing any cells in principle except normal self-cells. Cells expressing low levels of self MHC class I molecules such as tumor cells and foreign cells are killed, whereas normal self cells are neglected by NK cells. Although identities of activation receptors triggering NK activity are still unclear, recent studies have revealed molecules inhibiting cytotoxicity against normal self cells. In this review, we summarize current understanding of molecular basis for missing-self hypothesis and control mechanisms of NK cell activation.