A Role for cis Interaction between the Inhibitory Ly49A receptor and MHC class I for natural killer cell education

Immunity. 2009 Mar 20;30(3):337-47. doi: 10.1016/j.immuni.2008.12.019.


Natural killer (NK) cells show enhanced functional competence when they express inhibitory receptors specific for inherited major histocompatibility complex class I (MHC-I) molecules. Current models imply that NK cell education requires an interaction of inhibitory receptors with MHC-I expressed on other cells. However, the inhibitory Ly49A receptor can also bind MHC-I ligand on the NK cell itself (in cis). Here we describe a Ly49A variant, which can engage MHC-I expressed on other cells but not in cis. Even though this variant inhibited NK cell effector function, it failed to educate NK cells. The association with MHC-I in cis sequestered wild-type Ly49A, and this was found to relieve NK cells from a suppressive effect of unengaged Ly49A. These data explain how inhibitory MHC-I receptors can facilitate NK cell activation. They dissociate classical inhibitory from educating functions of Ly49A and suggest that cis interaction of Ly49A is necessary for NK cell education.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cells, Cultured
  • Flow Cytometry
  • Genetic Variation
  • Histocompatibility Antigens Class I / metabolism*
  • Killer Cells, Natural / immunology*
  • Lymphocyte Activation / immunology
  • Mice
  • Mice, Inbred C57BL
  • NK Cell Lectin-Like Receptor Subfamily A / genetics
  • NK Cell Lectin-Like Receptor Subfamily A / metabolism*


  • Histocompatibility Antigens Class I
  • NK Cell Lectin-Like Receptor Subfamily A