NKG2D ligands: key targets of the immune response

Trends Immunol. 2008 Aug;29(8):397-403. doi: 10.1016/j.it.2008.04.007. Epub 2008 Jul 3.


NKG2D is an activating receptor expressed by NK and T cells. NKG2D ligands show a restricted expression in normal tissues, but they are frequently overexpressed in cancer and infected cells. The binding of NKG2D to its ligands activates NK and T cells and promotes cytotoxic lysis of the cells expressing these molecules. The mechanisms involved in the expression of the ligands of NKG2D play a key role in the recognition of stressed cells by the immune system and represent a promising therapeutic target for improving the immune response against cancer or autoimmune disease. In this review, we analyse the recent advances in understanding the regulation of NKG2D ligand expression and their therapeutic implications.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cytotoxicity, Immunologic*
  • GPI-Linked Proteins
  • Gene Expression
  • Gene Expression Regulation / immunology*
  • Humans
  • Intercellular Signaling Peptides and Proteins / chemistry
  • Intercellular Signaling Peptides and Proteins / physiology*
  • Killer Cells, Natural / immunology
  • NK Cell Lectin-Like Receptor Subfamily K
  • Neoplasms / immunology
  • Receptors, Immunologic / chemistry
  • Receptors, Immunologic / physiology*
  • Receptors, Natural Killer Cell
  • T-Lymphocytes / immunology


  • GPI-Linked Proteins
  • Intercellular Signaling Peptides and Proteins
  • KLRK1 protein, human
  • NK Cell Lectin-Like Receptor Subfamily K
  • Receptors, Immunologic
  • Receptors, Natural Killer Cell
  • ULBP2 protein, human