Regulation of CD8+ T cell development by thymus-specific proteasomes
Regulation of CD8+ T cell development by thymus-specific proteasomes
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DOI：
10.1126/science.1141915
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发表时间：
2007-06-01
期刊：
影响因子：
56.9
通讯作者：
Tanaka, Keiji
中科院分区：
文献类型：
--
作者：
Murata, Shigeo;Sasaki, Katsuhiro;Tanaka, Keiji
蛋白酶体负责产生由免疫系统的第一类主要组织相容性复合体（MHC）分子呈现的肽。在这里，我们报告了一个以前未被识别的催化亚基称为β 5t的鉴定。β 5t仅在胸腺皮质上皮细胞中表达，该细胞负责发育中的胸腺细胞的阳性选择。尽管蛋白酶体的凝乳胰蛋白酶样活性被认为对产生MHC I类裂口的高亲和力肽很重要，但将β 5t掺入蛋白酶体以取代β 5或β 5i选择性地降低了这种活性。我们还发现β 5t缺陷小鼠胸腺CD8(+) T细胞发育缺陷。我们的研究结果表明，在胸腺选择过程中，β 5t在产生MHC i类限制性CD8(+) T细胞库中发挥了关键作用。
Proteasomes are responsible for generating peptides presented by the class I major histocompatibility complex (MHC) molecules of the immune system. Here, we report the identification of a previously unrecognized catalytic subunit called beta 5t. beta 5t is expressed exclusively in cortical thymic epithelial cells, which are responsible for the positive selection of developing thymocytes. Although the chymotrypsin-like activity of proteasomes is considered to be important for the production of peptides with high affinities for MHC class I clefts, incorporation of beta 5t into proteasomes in place of beta 5 or beta 5i selectively reduces this activity. We also found that beta 5t-deficient mice displayed defective development of CD8(+) T cells in the thymus. Our results suggest a key role for beta 5t in generating the MHC class I-restricted CD8(+) T cell repertoire during thymic selection.