Reference | ||
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Reference Type | Literature | IEDB_Reference:1037314 |
Title | The MHC-II peptidome of pancreatic islets identifies key features of autoimmune peptides. | |
Authors | Xiaoxiao Wan; Anthony N Vomund; Orion J Peterson; Alexander V Chervonsky; Cheryl F Lichti; Emil R Unanue | |
Affiliations | Department of Pathology and Immunology, Washington University School of Medicine, St Louis, MO, USA; Bursky Center for Human Immunology and Immunotherapy, Washington University School of Medicine, St Louis, MO, USA; Department of Pathology, School of Medicine, University of Chicago, Chicago, IL, USA; Department of Pathology and Immunology, Washington University School of Medicine, St Louis, MO, USA. clichti@wustl.edu; Bursky Center for Human Immunology and Immunotherapy, Washington University School of Medicine, St Louis, MO, USA. clichti@wustl.edu; Department of Pathology and Immunology, Washington University School of Medicine, St Louis, MO, USA. unanue@wustl.edu; Bursky Center for Human Immunology and Immunotherapy, Washington University School of Medicine, St Louis, MO, USA. unanue@wustl.edu. | |
Journal | Nat Immunol | |
Year | 2020 | |
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-A<sup>g7</sup> variant of MHC-II. The relevant peptides that induced pathogenic CD4<sup>+</sup> 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 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. | |
Curation Last Updated | 2023-08-19 04:27:54 |
Related Information | |
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Epitopes | |
Bcell Assays | 0 |
Tcell Assays | |
MHC Ligand Assays |