Sensing of cell stress by human γδ TCR-dependent recognition of annexin A2
Sensing of cell stress by human γδ TCR-dependent recognition of annexin A2
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DOI：
10.1073/pnas.1621052114
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发表时间：
2017-03-21
影响因子：
11.1
通讯作者：
Dechanet-Merville, Julie
中科院分区：
文献类型：
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作者：
Marlin, Romain;Pappalardo, Angela;Dechanet-Merville, Julie
人类γ δ T细胞通过T细胞受体（TCR）识别应激细胞构成第一道防线。然而，参与这种识别的分子决定因素和应激途径在很大程度上是未知的。在这里，我们表明肿瘤细胞暴露于各种应激情况导致肿瘤细胞被V.8Vd3 TCR识别。使用我们之前开发的一种策略来鉴定γ δ TCR的抗原配体，膜联蛋白A2被鉴定为V.8Vd3 TCR的直接配体，并被发现在以活性氧依赖的方式测试的应激情况下在肿瘤细胞上表达。此外，纯化的膜联蛋白A2能够刺激外周血单个核细胞内vd2 -负γ δ t细胞亚群的增殖，并且其他膜联蛋白A2特异性的vd2 -负γ δ t细胞克隆可以从外周血单个核细胞中获得。因此，我们提出膜联蛋白A2的膜暴露作为一些vd2 - γ δ T细胞的氧化应激信号，可能参与适应性应激监测。
Human gamma delta T cells comprise a first line of defense through T-cell receptor (TCR) recognition of stressed cells. However, the molecular determinants and stress pathways involved in this recognition are largely unknown. Here we show that exposure of tumor cells to various stress situations led to tumor cell recognition by a V.8Vd3 TCR. Using a strategy that we previously developed to identify antigenic ligands of gamma delta TCRs, annexin A2 was identified as the direct ligand of V.8Vd3 TCR, and was found to be expressed on tumor cells upon the stress situations tested in a reactive oxygen species-dependent manner. Moreover, purified annexin A2 was able to stimulate the proliferation of a Vd2neg gamma delta T-cell subset within peripheral blood mononuclear cells and other annexin A2-specific Vd2neg gamma delta T-cell clones could be derived from peripheral blood mononuclear cells. We thus propose membrane exposure of annexin A2 as an oxidative stress signal for some Vd2neg gamma delta T cells that could be involved in an adaptive stress surveillance.