A new self: MHC-class-I-independent natural-killer-cell self-tolerance

Nat Rev Immunol. 2005 May;5(5):363-74. doi: 10.1038/nri1603.


A fundamental tenet of the immune system is the requirement for lymphocytes to respond to transformed or infected cells while remaining tolerant of normal cells. Natural killer (NK) cells discriminate between self and non-self by monitoring the expression of MHC class I molecules. According to the 'missing-self' hypothesis, cells that express self-MHC class I molecules are protected from NK cells, but those that lack this self-marker are eliminated by NK cells. Recent work has revealed that there is another system of NK-cell inhibition, which is independent of MHC class I molecules. Newly discovered NK-cell inhibitory receptors that have non-MHC-molecule ligands broaden the definition of self as seen by NK cells.

Publication types

  • Review

MeSH terms

  • Animals
  • Antigens, Neoplasm / immunology
  • Autoimmunity / immunology
  • Cell Adhesion Molecules / immunology
  • Histocompatibility Antigens Class I / immunology
  • Humans
  • Killer Cells, Natural / immunology*
  • Lectins / metabolism
  • Receptors, Antigen / immunology
  • Self Tolerance / immunology*
  • Sialic Acids / metabolism


  • Antigens, Neoplasm
  • Cell Adhesion Molecules
  • Histocompatibility Antigens Class I
  • Lectins
  • Receptors, Antigen
  • Sialic Acids