Division of Immunology, Department of Biology, University of Constance, Konstanz, Germany.
Nat Rev Immunol. 2010 Jan;10(1):73-8. doi: 10.1038/nri2687. Epub 2009 Dec 11.
When cells are stimulated with pro-inflammatory cytokines, most of their constitutively expressed proteasomes are replaced with immunoproteasomes, which increase the production of peptides for presentation on MHC class I molecules. In addition, cortical thymic epithelial cells selectively express a type of proteasome known as the thymoproteasome that is required for the positive selection of thymocytes. Here, we discuss how these specialized types of proteasome shape the T cell receptor repertoire of cytotoxic T lymphocytes and propose that immunoproteasomes have functions, in addition to antigen processing, that influence cytokine production and T cell differentiation, survival and function. We also discuss how inhibitors of immunoproteasomes can suppress undesired T cell responses in autoimmune diseases.
当细胞受到促炎细胞因子刺激时，它们大多数组成型表达的蛋白酶体被免疫蛋白酶体取代，这增加了用于 MHC Ⅰ类分子呈递的肽的产生。此外，皮质胸腺上皮细胞选择性表达一种称为胸腺蛋白酶体的蛋白酶体，这是胸腺细胞阳性选择所必需的。在这里，我们讨论了这些专门类型的蛋白酶体如何塑造细胞毒性 T 淋巴细胞的 T 细胞受体库，并提出免疫蛋白酶体除了抗原加工外，还具有影响细胞因子产生和 T 细胞分化、存活和功能的功能。我们还讨论了免疫蛋白酶体抑制剂如何抑制自身免疫性疾病中不希望出现的 T 细胞反应。
