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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Proteasomes shape the repertoire of T cells participating in antigen-specific immune responses
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Proteasomes shape the repertoire of T cells participating in antigen-specific immune responses

机译：蛋白酶体决定参与抗原特异性免疫反应的T细胞的组成

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Differences in the cleavage specificities of constitutive proteasomes and immunoproteasomes significantly affect the generation of MHC class I ligands and therefore the activation of CD8-positive T cells. Based on these findings, we investigated whether proteasomal specificity also influences CD8-positive T cells during thymic selection by peptides derived from self proteins. We find that one of the self peptides responsible for positive selection of ovalbumin-specific OT-1 T cells, which is derived from the f-actin capping protein (Cp alpha 1), is efficiently generated only by immunoproteasomes. Furthermore, OT-1 mice backcrossed onto low molecular mass protein 7 (LMP7)-deficient mice show a 50% reduction of OT-1 cells. This deficiency is also observed after transfer of BM from OT-1 mice in LMP7-deficient mice and can be corrected by the injection of the Cp alpha 1 peptide. Interestingly, WT and LMP7-deficient mice mount comparable immune responses to the ovalbumin-derived epitope SIINFEKL. However, their cytotoxic T lymphocytes (CTL) differ in the use of T cell receptor V beta genes. CTL derived from WT mice use V beta 8 or V beta 5 (the latter is also used by OT-1 cells), whereas SIINFEKL-specific CTL from LMP7-deficient mice are exclusively V beta 8-positive. Taken together, our experiments provide strong evidence that proteasomal specificity shapes the repertoire of T cells participating in antigen-specific immune responses.
机译：组成型蛋白酶体和免疫蛋白酶体切割特异性的差异显着影响MHC I类配体的产生，从而影响CD8阳性T细胞的活化。基于这些发现，我们调查了蛋白酶体特异性是否也会在胸腺选择过程中通过衍生自自身蛋白的肽影响CD8阳性T细胞。我们发现负责卵白蛋白特异性OT-1 T细胞的积极选择的一种自身肽，它是从f-肌动蛋白加帽蛋白（Cp alpha 1）衍生出来的，仅由免疫蛋白酶体有效地产生。此外，回交到低分子量蛋白质7（LMP7）缺陷小鼠上的OT-1小鼠显示OT-1细胞减少了50％。在缺乏LMP7的小鼠中从OT-1小鼠转移BM后，也观察到这种缺陷，可以通过注射Cp alpha 1肽来纠正这种缺陷。有趣的是，WT和LMP7缺陷型小鼠对卵清蛋白来源的抗原决定簇SIINFEKL具有相当的免疫反应。但是，它们的细胞毒性T淋巴细胞（CTL）在使用T细胞受体Vβ基因方面有所不同。源自WT小鼠的CTL使用V beta 8或V beta 5（后者也被OT-1细胞使用），而来自LMP7缺陷小鼠的SIINFEKL特异性CTL仅具有V beta 8阳性。综上所述，我们的实验提供了有力的证据，证明蛋白酶体特异性决定了参与抗原特异性免疫反应的T细胞的组成。

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