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

Nat Immunol. 2002 Dec;3(12):1150-5. doi: 10.1038/ni857. Epub 2002 Nov 11.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Animals
  • Cytotoxicity, Immunologic
  • Histocompatibility Antigens Class I / immunology
  • Killer Cells, Natural / immunology*
  • Lymphocyte Activation / immunology*
  • Membrane Proteins / genetics
  • Membrane Proteins / immunology
  • Mice
  • Mutation
  • NK Cell Lectin-Like Receptor Subfamily K
  • Receptors, Immunologic / genetics
  • Receptors, Immunologic / immunology*
  • Receptors, Natural Killer Cell
  • Signal Transduction / immunology
  • T-Lymphocytes / immunology


  • Adaptor Proteins, Signal Transducing
  • Hcst protein, mouse
  • Histocompatibility Antigens Class I
  • Klrk1 protein, mouse
  • Membrane Proteins
  • NK Cell Lectin-Like Receptor Subfamily K
  • Receptors, Immunologic
  • Receptors, Natural Killer Cell
  • TYROBP protein, human