Composition of the HLA- DR- associated human thymus peptidome
Composition of the HLA- DR- associated human thymus peptidome
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DOI：
10.1002/eji.201243280
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发表时间：
2013-09-01
影响因子：
5.4
通讯作者：
Jaraquemada, Dolores
中科院分区：
文献类型：
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作者：
Collado, Javier A.;Alvarez, Inaki;Jaraquemada, Dolores
主要组织相容性复合物II类（MHC-II）分子结合并在抗原呈递细胞（APC）表面上展示抗原肽。在没有感染的情况下，APC上的MHC-II分子呈递自身肽并与CD 4（+）T细胞相互作用以维持耐受和稳态。在胸腺中，自身肽与由特定APC群体表达的MHC-II分子结合，所述APC群体专门用于T细胞选择的不同步骤。皮质上皮细胞呈递肽用于阳性选择，而髓质上皮细胞和树突状细胞负责肽呈递用于阴性选择。然而，关于胸腺中MHC分子呈递的肽的数据很少。在这里，我们应用质谱分析和鉴定MHC-II相关肽从五个新鲜的人胸腺样本。数据显示了多样的自身肽库，主要由预测的MHC-II高结合剂组成。尽管技术限制阻止肽的单细胞群体分析，但这些数据构成了HLA-II结合肽组的第一次直接评估，并提供了对该肽组如何产生以及如何驱动T细胞库形成的见解。
Major histocompatibility complex class II (MHC-II) molecules bind to and display antigenic peptides on the surface of antigen-presenting cells (APCs). In the absence of infection, MHC-II molecules on APCs present self-peptides and interact with CD4(+) T cells to maintain tolerance and homeostasis. In the thymus, self-peptides bind to MHC-II molecules expressed by defined populations of APCs specialised for the different steps of T-cell selection. Cortical epithelial cells present peptides for positive selection, whereas medullary epithelial cells and dendritic cells are responsible for peptide presentation for negative selection. However, few data are available on the peptides presented by MHC molecules in the thymus. Here, we apply mass spectrometry to analyse and identify MHC-II-associated peptides from five fresh human thymus samples. The data show a diverse self-peptide repertoire, mostly consisting of predicted MHC-II high binders. Despite technical limitations preventing single cell population analyses of peptides, these data constitute the first direct assessment of the HLA-II-bound peptidome and provide insight into how this peptidome is generated and how it drives T-cell repertoire formation.