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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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    Figure 1.

    Mouse NKG2D receptor complex. Mice express two alternatively spliced isoforms of NKG2D. NKG2D-L (long) is expressed as a disulfide-bonded homodimer that can associate with DAP10 homodimers on the surface of resting mouse NK cells and on activated (but not resting) CD8+ T cells. After activation, mouse NK cells express a NKG2D-S (short) isoform that can associate with homodimers of either DAP10 or DAP12. DAP10 contains a YINM motif capable of recruiting a p85 PI3-kinase, Vav-1, to the Grb2 signaling complex, whereas DAP12 contains a canonical ITAM, which can recruit Syk and ZAP70.

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    Figure 2.

    Human NKG2D receptor complex. Humans express a single full-length isoform of NKG2D constitutively as a disulfide-bonded homodimer on the cell surface of essentially all NK cells and CD8+ T cells, associated in a hexameric complex with two homodimers of the DAP10 signaling protein. Some individuals express an alternatively spliced NKG2D transcript that lacks the entire extracellular domain but retains the transmembrane and cytoplasmic domains of NKG2D (NKG2D-TR). NKG2D-TR homodimers and heterodimers of NKG2D-TR and full-length NKG2D apparently associate with DAP10 homodimers, but are retained within the cytoplasm and degraded, thereby diminishing cell surface expression of functional NKG2D complexes.

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    Figure 3.

    Schematic diagram showing all human and mouse NKG2D ligands identified to date.

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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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  • Article
    • Abstract
    • Disclosure of Potential Conflicts of Interest
    • Editor's Disclosures
    • CME Staff Planners' Disclosures
    • Learning Objectives
    • Acknowledgment of Financial or Other Support
    • 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
    • Therapeutic Opportunities
    • Disclosure of Potential Conflicts of Interest
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