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胰岛MHC-II肽组揭示出自身免疫肽的关键特征
作者:小柯机器人 发布时间:2020/3/22 19:53:24

美国华盛顿大学医学院Emil R. Unanue、Cheryl F. Lichti等研究人员合作根据胰岛MHC-II肽组鉴定出自身免疫肽的关键特征。该研究于2020年3月9日在线发表于《自然—免疫学》杂志。

研究人员测试了非肥胖糖尿病小鼠胰腺胰岛的免疫肽组,该小鼠根据主要组织相容性复合物II类(MHC-II)的I-Ag7变异体自发产生自身免疫性糖尿病。在糖尿病发作时诱导致病性CD4+T细胞的相关肽来源于胰岛素原。在胰腺淋巴结和脾脏的MHC-II肽组中也发现了这些肽。从胰岛素原来源的肽从它们在β细胞中的产生和胞吐作用到胰岛和周围部位的摄取和呈递都遵循这样的轨迹。这种途径产生了常规的表位,但也导致了翻译后修饰的肽的呈递,包括脱酰胺基序列。这些分析揭示了导致自身反应性的MHC-II肽组中限制性成分的关键特征。
 
据悉,引发自身免疫性疾病的自身抗原的性质已被广泛研究,但是大多数缺乏直接生化鉴定。要解决此问题,需要检测由特定自身免疫MHC-II分子展示的自身肽。
 
附:英文原文
 
Title: The MHC-II peptidome of pancreatic islets identifies key features of autoimmune peptides

Author: Xiaoxiao Wan, Anthony N. Vomund, Orion J. Peterson, Alexander V. Chervonsky, Cheryl F. Lichti, Emil R. Unanue

Issue&Volume: 2020-03-09

Abstract: The nature of autoantigens that trigger autoimmune diseases has been much discussed, but direct biochemical identification is lacking for most. Addressing this question demands unbiased examination of the self-peptides displayed by a defined autoimmune major histocompatibility complex class II (MHC-II) molecule. Here, we examined the immunopeptidome of the pancreatic islets in non-obese diabetic mice, which spontaneously develop autoimmune diabetes based on the I-Ag7 variant of MHC-II. The relevant peptides that induced pathogenic CD4+ T cells at the initiation of diabetes derived from proinsulin. These peptides were also found in the MHC-II peptidome of the pancreatic lymph nodes and spleen. The proinsulin-derived peptides followed a trajectory from their generation and exocytosis in β cells to uptake and presentation in islets and peripheral sites. Such a pathway generated conventional epitopes but also resulted in the presentation of post-translationally modified peptides, including deamidated sequences. These analyses reveal the key features of a restricted component in the self-MHC-II peptidome that caused autoreactivity.

DOI: 10.1038/s41590-020-0623-7

Source: https://www.nature.com/articles/s41590-020-0623-7

期刊信息

Nature Immunology:《自然—免疫学》,创刊于2000年。隶属于施普林格·自然出版集团,最新IF:23.53
官方网址:https://www.nature.com/ni/
投稿链接:https://mts-ni.nature.com/cgi-bin/main.plex