Regulation of ligands for the NKG2D activating receptor

Annu Rev Immunol. 2013:31:413-41. doi: 10.1146/annurev-immunol-032712-095951. Epub 2013 Jan 3.


NKG2D is an activating receptor expressed by all NK cells and subsets of T cells. It serves as a major recognition receptor for detection and elimination of transformed and infected cells and participates in the genesis of several inflammatory diseases. The ligands for NKG2D are self-proteins that are induced by pathways that are active in certain pathophysiological states. NKG2D ligands are regulated transcriptionally, at the level of mRNA and protein stability, and by cleavage from the cell surface. In some cases, ligand induction can be attributed to pathways that are activated specifically in cancer cells or infected cells. We review the numerous pathways that have been implicated in the regulation of NKG2D ligands, discuss the pathologic states in which those pathways are likely to act, and attempt to synthesize the findings into general schemes of NKG2D ligand regulation in NK cell responses to cancer and infection.

Publication types

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

MeSH terms

  • Animals
  • Humans
  • Killer Cells, Natural / immunology*
  • Killer Cells, Natural / metabolism*
  • Killer Cells, Natural / pathology
  • Ligands
  • Mice
  • NK Cell Lectin-Like Receptor Subfamily K / biosynthesis
  • NK Cell Lectin-Like Receptor Subfamily K / metabolism*
  • Natural Killer T-Cells / immunology
  • Natural Killer T-Cells / metabolism
  • Natural Killer T-Cells / pathology
  • Receptors, Antigen, T-Cell, gamma-delta / metabolism*


  • KLRK1 protein, human
  • Klrk1 protein, mouse
  • Ligands
  • NK Cell Lectin-Like Receptor Subfamily K
  • Receptors, Antigen, T-Cell, gamma-delta