PXD038758

PXD038758 is an original dataset announced via ProteomeXchange.

Title	Deamidation in human islets of Langerhans
Description	The β-cell plays a central role in the pathogenesis of T1D by neoantigen formation due to the generation of post-translational modifications, such as deamidation, being potential triggers for breaking immune tolerance. We report the detection by LC-MS/MS of 16 novel Gln and 27 novel Asn deamidations in 14 T1D-related proteins in inflammatory cytokine-stressed human islets of Langerhans. T-cell clones responsive against two Gln and three Asn deamidated peptides could be isolated from peripheral blood of T1D subjects. Ex vivo tetramer assays indicated higher T-cell frequencies in subjects with T1D compared to control subjects and a positive correlation between frequencies and insulin antibody levels at diagnosis and duration of disease for one Gln and two Asn deamidated peptides. These results highlight that inflammatory cytokine-exposed human islets are prone to both enzymatic and biochemical deamidation and suggest that both Gln and Asn deamidated peptides can promote the activation of CD4+ T cells in individuals with T1D. These findings add to the growing list of evidence that post-translational modifications undermine tolerance in T1D and may open the road for the development of new diagnostic and therapeutic applications for people living with T1D.
HostingRepository	PRIDE
AnnounceDate	2025-05-06
AnnouncementXML	Submission_2025-05-06_09:30:49.938.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Aisha Callebaut
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; deamidated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2022-12-12 22:26:15	ID requested
⏵ 1	2025-05-06 09:30:50	announced

Callebaut A, Guyer P, Derua R, Buitinga M, Manganaro A, Yi X, Sodr, é FMC, Vig S, Suleiman M, Marchetti P, Eizirik DL, Kent SC, Mathieu C, James EA, Overbergh L, CD4+ T Cells From Individuals With Type 1 Diabetes Respond to a Novel Class of Deamidated Peptides Formed in Pancreatic Islets. Diabetes, 73(5):728-742(2024) [pubmed]

10.2337/db23-0588;

submitter keyword: Human, pancreas, islets of Langerhans

Chantal Mathieu
contact affiliation	Catholic University of Leuven, Laboratory of Clinical and Experimental Endocrinology, Leuven, Belgium
contact email	chantal.mathieu@uzleuven.be
lab head
Aisha Callebaut
contact affiliation	Benaroya Research Institute
contact email	acallebaut@benaroyaresearch.org
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/2025/05/PXD038758

PRIDE project URI

• PRIDE
  1. PXD038758
     1. Label: PRIDE project
     2. Name: Deamidation in human islets of Langerhans