Up on the tightrope: natural killer cell activation and inhibition

Nat Immunol. 2008 May;9(5):495-502. doi: 10.1038/ni1581.


Natural killer (NK) cells circulate through the blood, lymphatics and tissues, on patrol for the presence of transformed or pathogen-infected cells. As almost all NK cell receptors bind to host-encoded ligands, signals are constantly being transmitted into NK cells, whether they interact with normal or abnormal cells. The sophisticated repertoire of activating and inhibitory receptors that has evolved to regulate NK cell activity ensures that NK cells protect hosts against pathogens, yet prevents deleterious NK cell-driven autoimmune responses. Here I highlight recent advances in our understanding of the structural properties and signaling pathways of the inhibitory and activating NK cell receptors, with a particular focus on the ITAM-dependent activating receptors, the NKG2D-DAP10 receptor complexes and the CD244 receptor system.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Amino Acid Motifs / immunology
  • Animals
  • Antigens, CD / immunology
  • Humans
  • Killer Cells, Natural / immunology*
  • Lymphocyte Activation
  • Membrane Proteins / immunology
  • Membrane Proteins / metabolism
  • NK Cell Lectin-Like Receptor Subfamily K
  • Receptors, Immunologic / antagonists & inhibitors
  • Receptors, Immunologic / chemistry
  • Receptors, Immunologic / immunology
  • Receptors, Immunologic / metabolism
  • Receptors, Natural Killer Cell
  • Signal Transduction / immunology
  • Tyrosine


  • Antigens, CD
  • HCST protein, human
  • Hcst protein, mouse
  • KLRK1 protein, human
  • Klrk1 protein, mouse
  • Membrane Proteins
  • NK Cell Lectin-Like Receptor Subfamily K
  • Receptors, Immunologic
  • Receptors, Natural Killer Cell
  • Tyrosine