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T Cells1
Fred Hutchinson Cancer Research Center, Seattle, WA 98109
Human 
T cells with the TCR variable region V1
occur mainly in epithelia and respond to stress-induced expression of
the MHC class I-related chains A and B, which have no function in Ag
presentation. MIC function as ligands for NKG2D-DAP10, an activating
receptor complex that triggers NK cells, costimulates CD8 
and
V9V2 T cells, and is required for
stimulation of V1 T cells. It is unresolved,
however, whether triggering of V1 TCRs is also
mediated by MIC or by unidentified cell surface components. Soluble
MICA tetramers were used as a binding reagent to demonstrate specific
interactions with various V1 TCRs expressed on
transfectants of a T cell line selected for lack of NKG2D. Tetramer
binding was restricted to TCRs derived from responder T cell clones
classified as reactive against a broad range of MIC-expressing target
cells and was abrogated when TCRs were composed of mismatched - and
-chains. These results and the inability of V1
T cells to respond to target cells expressing the ULBP/N2DL ligands of
NKG2D, which are highly divergent from MIC, indicate that MIC delivers
both the TCR-dependent signal 1 and the NKG2D-dependent costimulatory
signal 2. This dual function may serve to prevent erroneous T
cell activation by cross-reactive cell surface
determinants.
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