Licensing of natural killer cells by self-major histocompatibility complex class I

Immunol Rev. 2006 Dec;214:143-54. doi: 10.1111/j.1600-065X.2006.00458.x.


Natural killer (NK) cells have potent capacities to immediately kill cellular targets and produce cytokines that may potentially damage normal self-tissues unless they are kept in check. Such tolerance mechanisms are incompletely understood. Here we discuss recent studies suggesting that NK cells undergo a host major histocompatibility complex (MHC) class I-dependent functional maturation process, termed 'licensing'. Ironically, licensing directly involves inhibitory receptors that recognize target cell MHC class I molecules and block activation of NK cells in effector responses. This process results in two types of tolerant NK cells: functionally competent (licensed) NK cells, whose effector responses are inhibited by self-MHC class I molecules through the same receptors that conferred licensing, and functionally incompetent (unlicensed) NK cells.

Publication types

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

MeSH terms

  • Animals
  • Autoantigens / immunology*
  • Cell Differentiation / immunology
  • Histocompatibility Antigens Class I / immunology*
  • Humans
  • Killer Cells, Natural / cytology
  • Killer Cells, Natural / immunology*
  • Self Tolerance / immunology*


  • Autoantigens
  • Histocompatibility Antigens Class I