PXD030999 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Constrained self-antigen presentation in thymus underlies initiation of tissue-targeted autoimmunity |
Description | Presentation of tissue-restricted antigens (TRA) in the thymus is essentialfor establishing self-tolerancethrough elimination of autoreactive Tcells.It remains unclear why certain self T cells can bypassthymic selectionand become driversoftissue-specific autoimmunity. Herewe assessedthymic TRA presented by a major histocompatibility class II molecule (MHC-II) that confers genetic propensity to develop type 1 diabetes. This analysisestablished the thymic peptidome containing self-peptidesderivedfrom variousperipheral tissues,butalso revealed a disparity in the MHC-II epitoperepertoirebetween thymus and the target site of autoimmunity, the pancreatic islets.The thymic repertoire consistedof canonicalMHC-IIepitopes capable of enforcing central tolerance but lacked presentation of uniqueepitopes derived from unconventionalself-proteinprocessing orneoepitopes formed by post-translational modifications. Suchepitopes were noteworthily generatedin the isletsvia a tissue-intrinsic mechanism, crinophagy, and were recognized by CD4 T cells escaping central tolerance.These findings supportthat central tolerance mechanisms are effective but incomplete, as tissue-characteristic handling of self-antigens may broaden the peripheralrepertoire thatextends beyond the scope of thymic selection. |
HostingRepository | PRIDE |
AnnounceDate | 2024-10-22 |
AnnouncementXML | Submission_2024-10-22_06:55:38.405.xml |
DigitalObjectIdentifier | https://dx.doi.org/10.6019/PXD030999 |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Supported dataset by repository |
PrimarySubmitter | Cheryl Lichti |
SpeciesList | scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; |
ModificationList | cysteinylation (disulfide with free L-cysteine); dehydrated residue; monosodium salt; acetylated residue; monohydroxylated residue; deamidated residue; iodoacetamide derivatized residue |
Instrument | Orbitrap Fusion Lumos |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2022-01-16 14:00:49 | ID requested | |
1 | 2024-08-22 06:12:54 | announced | |
⏵ 2 | 2024-10-22 06:55:38 | announced | 2024-10-22: Updated project metadata. |
Publication List
Keyword List
submitter keyword: Mouse, Thymus, Crinosomes |
Contact List
Emil Unanue |
contact affiliation | Department of Pathology and Immunology Washington University School of Medicine St. Louis, MO 63110 |
contact email | unanue@wustl.edu |
lab head | |
Cheryl Lichti |
contact affiliation | Washington University |
contact email | clichti@wustl.edu |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD030999
- Label: PRIDE project
- Name: Constrained self-antigen presentation in thymus underlies initiation of tissue-targeted autoimmunity