T cell antigen receptor engagement and specificity in the recognition of stress-inducible MHC class I-related chains by human epithelial γδ T cells
T cell antigen receptor engagement and specificity in the recognition of stress-inducible MHC class I-related chains by human epithelial γδ T cells
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DOI：
10.4049/jimmunol.169.3.1236
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发表时间：
2002-08-01
影响因子：
4.4
通讯作者：
Spies, T
中科院分区：
文献类型：
--
作者：
Wu, J;Groh, V;Spies, T
具有TCR可变区V(delta)1的人γ δ T细胞主要出现在上皮细胞中，并对应激诱导的MHC i类相关链A和B的表达做出反应，这些链在Ag呈递中没有作用。MIC作为NKG2D-DAP10的配体，NKG2D-DAP10是一种激活受体复合物，可触发NK细胞，共同刺激CD8 α β和V(γ)9V(δ)2 γ - δ T细胞，并且是刺激V(δ)1 γ - δ T细胞所必需的。然而，尚不清楚V(δ)1 γ δ TCRs的触发是否也由MIC或未识别的细胞表面成分介导。可溶性MICA四聚体被用作结合试剂，以证明与在缺乏NKG2D的T细胞系的转染物上表达的各种V(delta)1 γ - δ TCRs的特异性相互作用。四聚体结合仅限于来自应答性T细胞克隆的tcr，这些T细胞克隆被归类为对多种表达mic的靶细胞具有反应性，当tcr由不匹配的γ链和δ链组成时，四聚体结合被取消。这些结果以及V(δ)1 γ δ T细胞无法对表达NKG2D的ULBP/N2DL配体的靶细胞做出反应（这些配体与MIC高度不同）表明，MIC既传递tcr依赖性信号I，也传递NKG2D依赖性共刺激信号2。这种双重功能可能有助于防止错误的γ - δ T细胞被交叉反应的细胞表面决定因子激活。
Human gammadelta T cells with the TCR variable region V(delta)1 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 alphabeta and V(gamma)9V(delta)2 gammadelta T cells, and is required for stimulation of V(delta)1 gammadelta T cells. It is unresolved, however, whether triggering of V(delta)1 gammadelta 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 V(delta)1 gammadelta 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 gamma- and delta-chains. These results and the inability of V(delta)1 gammadelta 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 I and the NKG2D-dependent costimulatory signal 2. This dual function may serve to prevent erroneous gammadelta T cell activation by cross-reactive cell surface determinants.