NK cell activation: distinct stimulatory pathways counterbalancing inhibitory signals

Hum Immunol. 2000 Jan;61(1):18-27. doi: 10.1016/s0198-8859(99)00160-3.


A delicate balance between positive and negative signals regulates NK cell effector function. Activation of NK cells may be initiated by the triggering of multiple adhesion or costimulatory molecules, and can be counterbalanced by inhibitory signals induced by receptors for MHC class I. A common pathway of inhibitory signaling is provided by immunoreceptor tyrosine-based inhibitory motifs (ITIMs) in the cytoplasmic domains of these receptors which 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 function. Several NK receptors using novel adaptors with immunoreceptor tyrosine-based activation motifs (ITAMs) and with PI 3-kinase recruiting motifs have been implicated in NK cell stimulation.

Publication types

  • Review

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Animals
  • Antigens, CD*
  • Histocompatibility Antigens Class I / immunology
  • Histocompatibility Antigens Class I / metabolism
  • Humans
  • Killer Cells, Natural / immunology*
  • Lymphocyte Activation*
  • Membrane Glycoproteins / immunology
  • Membrane Glycoproteins / metabolism
  • Membrane Proteins
  • Mice
  • Receptors, Immunologic / immunology*
  • Receptors, Immunologic / metabolism
  • Signaling Lymphocytic Activation Molecule Family


  • Adaptor Proteins, Signal Transducing
  • Antigens, CD
  • CD244 protein, human
  • Cd244a protein, mouse
  • Histocompatibility Antigens Class I
  • Membrane Glycoproteins
  • Membrane Proteins
  • Receptors, Immunologic
  • Signaling Lymphocytic Activation Molecule Family
  • TYROBP protein, human