Molecular Immunology laboratory, the Francis Crick Institute, NW1 1AT London, United Kingdom; Centre for Inflammation Biology and Cancer Immunology & Peter Gorer Department of Immunobiology, King's College London, SE1 1UL London, United Kingdom.
Research group of Quantitative System Biology, Max-Planck-Institute for Multidisciplinary Sciences, 37077 Göttingen, Germany.
Immunol Lett. 2024 Oct;269:106899. doi: 10.1016/j.imlet.2024.106899. Epub 2024 Jul 15.
The thymus is the organ where functional and self-tolerant T cells are selected through processes of positive and negative selection before migrating to the periphery. The antigenic peptides presented on MHC class I molecules of thymic epithelial cells (TECs) in the cortex and medulla of the thymus are key players in these processes. It has been theorized that these cells express different proteasome isoforms, which generate MHC class I immunopeptidomes with features that differentiate cortex and medulla, and hence positive and negative CD8 T cell selection. This theory is largely based on mouse models and does not consider the large variety of noncanonical antigenic peptides that could be produced by proteasomes and presented on MHC class I molecules. Here, we review the multi-omics, biochemical and cellular studies carried out on mouse models and human thymi to investigate their content of proteasome isoforms, briefly summarize the implication that noncanonical antigenic peptide presentation in the thymus could have on CD8 T cell repertoire and put these aspects in the larger framework of anatomical and immunological differences between these two species.
胸腺是一个器官，在成熟迁移到外周之前，功能性和自身耐受的 T 细胞通过阳性和阴性选择过程在此被筛选。在胸腺皮质和髓质的胸腺上皮细胞（TEC）的 MHC Ⅰ类分子上呈递的抗原肽是这些过程中的关键因素。据推测，这些细胞表达不同的蛋白酶体同工型，其产生的 MHC Ⅰ类免疫肽组具有区分皮质和髓质的特征，进而区分阳性和阴性 CD8 T 细胞选择。该理论主要基于小鼠模型，并未考虑到可能由蛋白酶体产生并在 MHC Ⅰ类分子上呈递的大量非典型抗原肽。在这里，我们综述了在小鼠模型和人类胸腺中进行的多组学、生化和细胞研究，以研究它们的蛋白酶体同工型含量，简要总结了胸腺中非典型抗原肽呈递对 CD8 T 细胞库的影响，并将这些方面置于这两个物种之间的解剖学和免疫学差异的更大框架内。
