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。
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
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:31.25
官方网址:https://www.nature.com/ni/
投稿链接:https://mts-ni.nature.com/cgi-bin/main.plex
本期文章:《自然—免疫学》:Online/在线发表