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NKG2D recruits two distinct adapters to trigger NK cell activation and costimulation

Nature Immunologyvolume 3pages11501155 (2002) | Download Citation

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Abstract

NKG2D is a receptor on natural killer (NK) cells and cytotoxic T lymphocytes that binds major histocompatibility complex (MHC) class I–like ligands expressed primarily on virally infected and neoplastic cells. In vitro studies indicate that NKG2D provides costimulation through an associated adapter, DAP10, which recruits phosphatidylinositol-3 kinase. Here we show that in DAP10-deficient mice, CD8+ T cells lack NKG2D expression and are incapable of mounting tumor-specific responses. However, DAP10-deficient NK cells express a functional NKG2D receptor due to the association of NKG2D with another adapter molecule, DAP12 (also known as KARAP), which recruits protein tyrosine kinases. Thus, NKG2D is a versatile receptor that, depending on the availability of adapter partners, mediates costimulation in T cells and/or activation in NK cells.

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Acknowledgements

We thank K. Rajewsky for the Cre-transgenic mice, T. Miyazaki for the original vial of E14.1 cells, S. Kuschert for blastocyst injection, E. Wagner and colleagues for animal care at the former Basel Institute for Immunology and C. Strader for technical assistance. E. L. H. was supported by a training grant from the Cancer Research Institute and W. M. Y. was supported by NIH grants, the Barnes-Jewish Hospital Foundation and the Howard Hughes Medical Institute.

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Affiliations

  1. Department of Pathology and Immunology, Washington University School of Medicine, 660 S. Euclid, St. Louis, 63110, MO, USA

    • Susan Gilfillan
    • , Marina Cella
    •  & Marco Colonna
  2. Rheumatology Division, Department of Medicine, Howard Hughes Medical Institute, Barnes-Jewish Hospital and Washington University School of Medicine, 660 S. Euclid, St. Louis, 63110, MO, USA

    • Emily L. Ho
    •  & Wayne M. Yokoyama

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The authors declare no competing financial interests.

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Correspondence to Marco Colonna.

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https://doi.org/10.1038/ni857

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