PXD041227

PXD041227 is an original dataset announced via ProteomeXchange.

Title	Ubiquitin Thioesterase OTUB2 is An Endoplasmic Reticulum Stress-associated β Cell Autoantigen Targeted by CD8+ T cells in Type 1 Diabetes
Description	Autoreactive CD8+ T cell plays a key role in the pathogenesis of Type 1 diabetes (T1D), but the antigen spectrum that activate autoreactive CD8+ T cells is still not completely clear. Endoplasmic reticulum stress（ERS）has been implicated in the generation of β cell autoantigens and the enhanced immune visibility of β cells to autoreactive T cells. Here, we in-depth analyzed the major histocompatibility complex class I (MHC-I) associated immunopeptidome (MIP) of islets β cell under steady-state and ERS-state, and found couples of peptides exclusively present in the MIP of β cell line under ERS state. Among them, peptide OTUB258-66 derived from ubiquitin thioesterase OTUB2 showed immunodominance in NOD mice, and autoreactive CD8+ T cells targeting OTUB258-66 were diabetogenic in NOD mice. High glucose intake upregulated the expression of OTUB2 in the pancreas and amplified the OTUB258-66-specific CD8+ T cell response in NOD mice. Repeated administration with OTUB258-66 significantly reduced the incidence of T1D in NOD mice. This study not only provides an explanation for the role of ERS induced by environmental factors such as high glucose intake in promoting β cell autoimmune injury, but also provides a novel ERS-associated β cell autoantigens for developing specific immune intervention in prevention and treatment of T1D.
HostingRepository	PRIDE
AnnounceDate	2024-05-24
AnnouncementXML	Submission_2024-05-24_01:14:32.270.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	lina wang
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2023-03-30 14:55:18	ID requested
⏵ 1	2024-05-24 01:14:33	announced

10.1038/s41423-024-01150-0;

Wang L, Yang S, Zhu G, Li J, Meng G, Chen X, Zhang M, Wang S, Li X, Pan Y, Huang Y, Wang L, Wu Y, Immunopeptidome mining reveals a novel ERS-induced target in T1D. Cell Mol Immunol, 21(6):604-619(2024) [pubmed]

submitter keyword: OTUB2, Endoplasmic Reticulum Stress, Type 1 Diabetes, CD8+ T-cell.

Li Wang
contact affiliation	Army Medical University (Third Military Medical University)
contact email	liwang118@tmmu.edu.cn
lab head
lina wang
contact affiliation	no
contact email	1481752769@qq.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD041227
     1. Label: PRIDE project
     2. Name: Ubiquitin Thioesterase OTUB2 is An Endoplasmic Reticulum Stress-associated β Cell Autoantigen Targeted by CD8+ T cells in Type 1 Diabetes