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首页> 外文期刊>Nature immunology >TCR affinity for thymoproteasome-dependent positively selecting peptides conditions antigen responsiveness in CD8(+) T cells
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TCR affinity for thymoproteasome-dependent positively selecting peptides conditions antigen responsiveness in CD8(+) T cells

机译:胸腺蛋白酶依赖的积极选择肽的TCR亲和力调节CD8(+)T细胞中的抗原反应性

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摘要

In the thymus, low-affinity T cell antigen receptor (TCR) engagement facilitates positive selection of a useful T cell repertoire. Here we report that TCR responsiveness of mature CD8(+) T cells is fine tuned by their affinity for positively selecting peptides in the thymus and that optimal TCR responsiveness requires positive selection on major histocompatibility complex class I-associated peptides produced by the thymoproteasome, which is specifically expressed in the thymic cortical epithelium. Thymoproteasome-independent positive selection of monoclonal CD8(+) T cells results in aberrant TCR responsiveness, homeostatic maintenance and immune responses to infection. These results demonstrate a novel aspect of positive selection, in which TCR affinity for positively selecting peptides produced by thymic epithelium determines the subsequent antigen responsiveness of mature CD8(+) T cells in the periphery.
机译:在胸腺中,低亲和力的T细胞抗原受体(TCR)参与有助于积极选择有用的T细胞库。在这里我们报告说,成熟的CD8(+)T细胞的TCR响应能力通过其对在胸腺中正向选择肽段的亲和力进行了微调,并且最佳TCR响应度需要对由胸腺蛋白酶体产生的主要组织相容性复杂的I类相关肽段进行正向选择,在胸腺皮质上皮中特异性表达。不依赖胸腺蛋白酶体的阳性选择的单克隆CD8(+)T细胞导致异常的TCR反应性,体内稳态维持和对感染的免疫反应。这些结果证明了积极选择的一个新方面,其中TCR亲和力积极选择由胸腺上皮细胞产生的肽决定了周边成熟CD8(+)T细胞的后续抗原反应性。

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