Nedjic Jelena, Aichinger Martin, Klein Ludger
Institute for Immunology, Ludwig-Maximilians-University, Munich, Germany.
Autophagy. 2008 Nov;4(8):1090-2. doi: 10.4161/auto.7139. Epub 2008 Nov 6.
During T cell development in the thymus, scanning of peptide/major histocompatibility (MHC) molecule complexes on the surface of thymic epithelial cells ensures that only useful (self-MHC restricted) and harmless (self-tolerant) thymocytes survive. In recent years, a number of distinct cell-biological features of thymic epithelial cells have been unraveled that may have evolved to render these cells particularly suited for T cell selection, e.g., cortical epithelial cells use unique proteolytic enzymes for the generation of MHC/peptide complexes, whereas medullary epithelial cells "promiscuously" express otherwise tissue-restricted self-antigens. We recently showed that macroautophagy in thymic epithelial cells contributes to CD4 T cell selection and is essential for the generation of a self-tolerant T cell repertoire. We propose that the unusually high constitutive levels of autophagy in thymic epithelial cells deliver endogenous proteins to MHC class II molecules for both positive and negative selection of developing thymocytes.
在胸腺中T细胞发育过程中，对胸腺上皮细胞表面的肽/主要组织相容性复合体（MHC）进行扫描，可确保只有有用的（自我MHC限制的）和无害的（自我耐受的）胸腺细胞存活。近年来，胸腺上皮细胞的许多独特细胞生物学特征已被揭示，这些特征可能是为使这些细胞特别适合T细胞选择而进化出来的，例如，皮质上皮细胞使用独特的蛋白水解酶来生成MHC/肽复合物，而髓质上皮细胞“随意地”表达原本组织限制性的自身抗原。我们最近发现，胸腺上皮细胞中的巨自噬有助于CD4 T细胞的选择，并且对于产生自我耐受的T细胞库至关重要。我们提出，胸腺上皮细胞中异常高的自噬组成水平将内源性蛋白质递呈给II类MHC分子，以用于发育中胸腺细胞的阳性和阴性选择。
