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Masters of Immunology

NKG2D Receptor and Its Ligands in Host Defense

Lewis L. Lanier
Lewis L. Lanier
Department of Microbiology and Immunology, University of California San Francisco, San Francisco, California.
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  • For correspondence: lewis.lanier@ucsf.edu
DOI: 10.1158/2326-6066.CIR-15-0098 Published June 2015
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Abstract

NKG2D is an activating receptor expressed on the surface of natural killer (NK) cells, CD8+ T cells, and subsets of CD4+ T cells, invariant NKT cells (iNKT), and γδ T cells. In humans, NKG2D transmits signals by its association with the DAP10 adapter subunit, and in mice alternatively spliced isoforms transmit signals either using DAP10 or DAP12 adapter subunits. Although NKG2D is encoded by a highly conserved gene (KLRK1) with limited polymorphism, the receptor recognizes an extensive repertoire of ligands, encoded by at least eight genes in humans (MICA, MICB, RAET1E, RAET1G, RAET1H, RAET1I, RAET1L, and RAET1N), some with extensive allelic polymorphism. Expression of the NKG2D ligands is tightly regulated at the level of transcription, translation, and posttranslation. In general, healthy adult tissues do not express NKG2D glycoproteins on the cell surface, but these ligands can be induced by hyperproliferation and transformation, as well as when cells are infected by pathogens. Thus, the NKG2D pathway serves as a mechanism for the immune system to detect and eliminate cells that have undergone “stress.” Viruses and tumor cells have devised numerous strategies to evade detection by the NKG2D surveillance system, and diversification of the NKG2D ligand genes likely has been driven by selective pressures imposed by pathogens. NKG2D provides an attractive target for therapeutics in the treatment of infectious diseases, cancer, and autoimmune diseases. Cancer Immunol Res; 3(6); 575–82. ©2015 AACR.

  • Received April 10, 2015.
  • Accepted April 14, 2015.
  • ©2015 American Association for Cancer Research.
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Cancer Immunology Research: 3 (6)
June 2015
Volume 3, Issue 6
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NKG2D Receptor and Its Ligands in Host Defense
Lewis L. Lanier
Cancer Immunol Res June 1 2015 (3) (6) 575-582; DOI: 10.1158/2326-6066.CIR-15-0098

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NKG2D Receptor and Its Ligands in Host Defense
Lewis L. Lanier
Cancer Immunol Res June 1 2015 (3) (6) 575-582; DOI: 10.1158/2326-6066.CIR-15-0098
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    • Introduction
    • NKG2D Genes and Proteins
    • NKG2D Ligand Genes and Proteins
    • Activation of NK Cells and T Cells by NKG2D
    • NKG2D in Immunity to Infectious Diseases and Cancer
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