Interaction of Toll-Like Receptors with the Molecular Chaperone Gp96 Is Essential for Its Activation of Cytotoxic T Lymphocyte Response.
Interaction of Toll-Like Receptors with the Molecular Chaperone Gp96 Is Essential for Its Activation of Cytotoxic T Lymphocyte Response.
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Toll 样受体与分子伴侣 Gp96 的相互作用对于激活细胞毒性 T 淋巴细胞反应至关重要
DOI：
10.1371/journal.pone.0155202
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Meng S
中科院分区：
文献类型：
--
作者：
Liu W;Chen M;Li X;Zhao B;Hou J;Zheng H;Qiu L;Li Z;Meng S
在啮齿动物模型和临床试验中，热休克蛋白gp 96激发特异性T细胞对其伴侣肽的应答以对抗癌症和感染性疾病。尽管人们认为gp 96通过Toll样受体（TLR）子集诱导的先天免疫和通过抗原递呈诱导的适应性免疫对于引发有效的T细胞反应都很重要，但缺乏直接证据表明gp 96介导的TLR激活的作用与其功能性T细胞激活有关。在这里，我们报告说，gp 96含有突变的TLR结合域未能激活巨噬细胞，但肽的介绍是不受影响的。此外，我们发现，肽特异性T细胞反应，以及由gp 96诱导的抗肿瘤T细胞免疫，严重受损时，TLR结合结构域突变。这些数据证明了gp 96-TLR相互作用在引发T细胞免疫中的重要作用，并为gp 96介导的先天性免疫与获得性免疫的偶联提供了进一步的分子基础。
The heat shock protein gp96 elicits specific T cell responses to its chaperoned peptides against cancer and infectious diseases in both rodent models and clinical trials. Although gp96-induced innate immunity, via a subset of Toll like receptors (TLRs), and adaptive immunity, through antigen presentation, are both believed to be important for priming potent T cell responses, direct evidence for the role of gp96-mediated TLR activation related to its functional T cell activation is lacking. Here, we report that gp96 containing mutations in its TLR-binding domain failed to activate macrophages, but peptide presentation was unaffected. Moreover, we found that peptide-specific T cell responses, as well as antitumor T cell immunity induced by gp96, are severely impaired when the TLR-binding domain is mutated. These data demonstrate the essential role of the gp96-TLR interaction in priming T cell immunity and provide further molecular basis for the coupling of gp96-mediated innate with adaptive immunity.