T cell antigen receptor engagement and specificity in the recognition of stress-inducible MHC class I-related chains by human epithelial gamma delta T cells.
T cell antigen receptor engagement and specificity in the recognition of stress-inducible MHC class I-related chains by human epithelial gamma delta T cells.
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发表时间：
2002
影响因子：
4.4
通讯作者：
Jennifer D. Wu;V. Groh;T. Spies
中科院分区：
文献类型：
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作者：
Jennifer D. Wu;V. Groh;T. Spies
具有TCR可变区V(Delta)1的人Gamma Delta T细胞主要存在于上皮细胞中，并对MHC I类相关链A和B的表达做出反应，这些链在抗原提呈中没有作用。MIC的功能是作为NKG2D-DAP10的配体，NKG2D-DAP10是一种激活的受体复合体，可以触发NK细胞，共刺激CD8αβ和V(Gamma)9V(Delta)2 Gamma Delta T细胞，并且是刺激V(Delta)1 Gamma Delta T细胞所必需的。然而，V(Delta)1伽马增量TCRs的触发是否也是由MIC或未知的细胞表面成分介导的，目前尚不清楚。用可溶性MICA四聚体作为结合剂，研究了与NKG2D缺失的T细胞系的转染体上表达的各种V(Delta)1γDelta TCR的特异性相互作用。四聚体结合仅限于来自应答T细胞克隆的TCR，分类为对广泛表达MIC的靶细胞具有反应，当TCR由不匹配的伽马链和三角链组成时，四聚体结合被取消。这些结果和V(Delta)1γDelta T细胞对表达NKG2D的ULBP/N2DL配体的靶细胞的反应能力与MIC高度不同，表明MIC同时传递TCR依赖的信号1和NKG2D依赖的共刺激信号2。这种双重功能可能有助于防止交叉反应细胞表面决定因素错误地激活Gamma Delta T细胞。
Human gamma delta 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 alpha beta and V(gamma)9V(delta)2 gamma delta T cells, and is required for stimulation of V(delta)1 gamma delta T cells. It is unresolved, however, whether triggering of V(delta)1 gamma delta 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 gamma delta 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 gamma delta 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 gamma delta T cell activation by cross-reactive cell surface determinants.