PXD030999-2

PXD030999 is an original dataset announced via ProteomeXchange.

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

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.

10.6019/PXD030999;

submitter keyword: Mouse, Thymus, Crinosomes

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

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PRIDE project URI

• PRIDE
  1. PXD030999
     1. Label: PRIDE project
     2. Name: Constrained self-antigen presentation in thymus underlies initiation of tissue-targeted autoimmunity