The role of the NKG2D immunoreceptor in immune cell activation and natural killing

Amanda M. Jamieson, Andreas Diefenbach, Christopher W. McMahon, Na Xiong, James R. Carlyle, David H. Raulet

Research output: Contribution to journalArticlepeer-review

552 Scopus citations


Little is known concerning the stimulatory receptors responsible for tumor cell lysis by NK cells. We generated a monoclonal antibody specific for murine NKG2D in order to investigate its function. Blocking of NKG2D inhibited natural cytotoxicity of all tumor cells tested that express ligands for the receptor. Staining analysis showed that NKG2D is also expressed by activated CD8+ T cells and macrophages, and subsets of TCRγδ+ and NK1.1+ T cells. Contradicting reports that NKG2D is solely a costimulatory receptor, we observed that cross-linking of NKG2D directly stimulates NK cells and activated macrophages. In contrast, NKG2D costimulates activated CD8+ T cells. Thus, NKG2D engagement directly stimulates NK cells and macrophages, costimulates CD8+ T cells, and plays a substantial role in natural killing.

Original languageEnglish (US)
Pages (from-to)19-29
Number of pages11
Issue number1
StatePublished - 2002

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases


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