PXD024400

PXD024400 is an original dataset announced via ProteomeXchange.

Title	Blood leukocytes recapitulate diabetogenic peptide-MHC-II complexes displayed in the pancreatic islets
Description	Assessing the self-peptides presented by susceptible major histocompatibility complex (MHC) molecules is crucial for evaluating the pathogenesis and therapeutics of tissue-specific autoimmune diseases. However, direct examination of such MHC-bound peptides displayed in the target organ remains largely impractical. Here, we demonstrate that the blood leukocytes from non-obese diabetic (NOD) mice presented peptide epitopes to autoreactive CD4 T cells. These peptides were bound to the autoimmune class II MHC molecule, I-Ag7, and originated from insulin B-chain and C-peptide. The presentation required a glucose challenge, which stimulated the release of insulin peptides from pancreatic islets. The circulating leukocytes, especially the B cells, promptly captured and presented these peptides. Although canonical intracellular processing of insulin was involved in the presentation, extracellular binding of catabolized insulin products to I-Ag7 gave rise to a unique pathogenic epitope. Administration of monoclonal antibodies recognizing insulin B-chain abolished the presentation and diminished diabetes incidence. Mass spectrometry analysis of the leukocyte MHC-II peptidomes revealed a series of beta cell derived peptides, with identical sequences to those previously in the islet MHC-II peptidome. Thus, the WBC peptidome echoes that found in islets and serves to identify immunogenic peptides in an otherwise inaccessible tissue.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_05:20:24.924.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD024400
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	monohydroxylated residue; deamidated residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2021-02-26 06:19:08	ID requested
1	2021-03-25 23:12:47	announced
⏵ 2	2024-10-22 05:20:25	announced	2024-10-22: Updated project metadata.

10.6019/PXD024400;

submitter keyword: blood leukocytes, NOD mouse, MHC-II peptidome

Cheryl Lichti
contact affiliation	Washington University School of Medicine Department of Pathology & Immunology 425 S. Euclid, Campus Box 8118 St. Louis, MO 63110
contact email	clichti@wustl.edu
lab head
Cheryl Lichti
contact affiliation	Washington University
contact email	clichti@wustl.edu
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2021/03/PXD024400

PRIDE project URI

• PRIDE
  1. PXD024400
     1. Label: PRIDE project
     2. Name: Blood leukocytes recapitulate diabetogenic peptide-MHC-II complexes displayed in the pancreatic islets