NKG2D recruits two distinct adapters to trigger NK cell activation and costimulation
S Gilfillan, EL Ho, M Cella, WM Yokoyama… - Nature …, 2002 - nature.com
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 …
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 …
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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