NKG2D recruits two distinct adapters to trigger NK cell activation and costimulation.
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.
Gilfillan
Susan
S
Department of Pathology and Immunology, Washington University School of Medicine, 660 S. Euclid, St. Louis, MO 63110, USA.
Ho
Emily L
EL
Cella
Marina
M
Yokoyama
Wayne M
WM
Colonna
Marco
M
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D003602:Cytotoxicity, Immunologic; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology*; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology; D051379:Mice; D009154:Mutation; D055655:NK Cell Lectin-Like Receptor Subfamily K; D011971:Receptors, Immunologic / Q000235:genetics / Q000276:immunology*; D055607:Receptors, Natural Killer Cell; D015398:Signal Transduction / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
D048868:Adaptor Proteins, Signal Transducing; C492355:Hcst protein, mouse; D015395:Histocompatibility Antigens Class I; C527086:Klrk1 protein, mouse; D008565:Membrane Proteins; D055655:NK Cell Lectin-Like Receptor Subfamily K; D011971:Receptors, Immunologic; D055607:Receptors, Natural Killer Cell; C110546:TYROBP protein, human