NK cell activation: Distinct stimulatory pathways counterbalancing inhibitory signals

A delicate balance between positive and negative signals regulates NK cell effector function. Activation of NK cells may be initiated by the triggerin g of multiple adhesion or costimulatory molecules, and can be counterbalanc ed by inhibitory signals induced by receptors for MHC class I. A common pat hway of inhibitory signaling is provided by immunoreceptor tyrosine-based i nhibitory motifs (ITIMs) in the cytoplasmic domains of. these receptors whi ch mediate the recruitment of SH2 domain-bearing tyrosine phosphate-1 (SHP- 1). In contrast to the extensive progress that. has been made regarding the negative regulation of NK cell function, our knowledge of the signals that activate NK cells is still poor. Recent studies of the activating receptor complexes have shed new light on the induction of NK cell effector functio n. Several NK receptors using novel adaptors with Immunoreceptor tyrosine-b ased activation motifs (ITAMs) and with PI 3-kinase recruiting motifs have been implicated in NK cell stimulation. Human Immunology 61, 18-27 (2000). (C) American Society for Histocompatibility and Immunogenetics, 2000. Publi shed by Elsevier Science Inc.