| First Author | Wan X | Year | 2020 |
| Journal | Nat Immunol | Volume | 21 |
| Issue | 4 | Pages | 455-463 |
| PubMed ID | 32152506 | Mgi Jnum | J:306901 |
| Mgi Id | MGI:6706724 | Doi | 10.1038/s41590-020-0623-7 |
| Citation | Wan X, et al. (2020) The MHC-II peptidome of pancreatic islets identifies key features of autoimmune peptides. Nat Immunol 21(4):455-463 |
| abstractText | 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(g7) 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 beta 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. |
