Exploring the MHC-peptide matrix of central tolerance in the human thymus
Exploring the MHC-peptide matrix of central tolerance in the human thymus
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DOI：
10.1038/ncomms3039
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发表时间：
2013-06-01
影响因子：
16.6
通讯作者：
Stoeckle, Christina
中科院分区：
文献类型：
--
作者：
Adamopoulou, Eleni;Tenzer, Stefan;Stoeckle, Christina
自从发现对自身的中枢耐受性通过与胸腺抗原呈递细胞上的自身肽主要组织相容性复合物的相互作用强加于胸腺中发育中的T细胞以来，免疫学家一直在推测这些肽的性质，特别是在人类中。在这里，阐明迄今未知的人类胸腺肽库，我们分析肽洗脱分离的胸腺树突状细胞，树突状细胞耗尽的抗原呈递细胞和整个胸腺。对842种天然主要组织相容性复合物I和II配体的生物信息学分析揭示了主要组织相容性复合物I类和II类途径之间的显著串扰，以及个体之间以及不同抗原呈递细胞之间的源蛋白表达差异。此外，一些自身免疫和肿瘤相关的肽，从烯醇化酶和波形蛋白，例如，在健康的胸腺。302肽直接来源于阴性选择树突状细胞，从而提供了在人体胸腺中的肽基质的第一个全局视图，在体内施加自身耐受性。
Ever since it was discovered that central tolerance to self is imposed on developing T cells in the thymus through their interaction with self-peptide major histocompatibility complexes on thymic antigen-presenting cells, immunologists have speculated about the nature of these peptides, particularly in humans. Here, to shed light on the so-far unknown human thymic peptide repertoire, we analyse peptides eluted from isolated thymic dendritic cells, dendritic cell-depleted antigen-presenting cells and whole thymus. Bioinformatic analysis of the 842 identified natural major histocompatibility complex I and II ligands reveals significant crosstalk between major histocompatibility complex-class I and II pathways and differences in source protein representation between individuals as well as different antigen-presenting cells. Furthermore, several autoimmune- and tumour-related peptides, from enolase and vimentin for example, are presented in the healthy thymus. 302 peptides are directly derived from negatively selecting dendritic cells, thus providing the first global view of the peptide matrix in the human thymus that imposes self-tolerance in vivo.