PXD045265

PXD045265 is an original dataset announced via ProteomeXchange.

Title	HLA-peptidome of human beta cells exposed to interferon-alpha
Description	Interferon (IFN)-α is the earliest cytokine signature observed in individuals at risk for type 1 diabetes (T1D), but its effect on the repertoire of HLA Class I (HLA-I)-bound peptides presented by pancreatic β-cells is unknown. Using immunopeptidomics, we characterized the peptide/HLA-I presentation in in-vitro resting and IFN-α-exposed β-cells. IFN-α increased HLA-I expression and peptide presentation, including neo-sequences derived from alternative mRNA splicing, post-translational modifications - notably glutathionylation - and protein cis-splicing. This antigenic landscape relied on processing by both the constitutive and immune proteasome. The resting β-cell immunopeptidome was dominated by HLA-A-restricted ligands. However, IFN-α only marginally upregulated HLA-A and largely favored HLA-B, translating into a major increase in HLA-B-restricted peptides and into an increased activation of HLA-B-restricted vs. HLA-A-restricted CD8+ T-cells. A preferential HLA-B hyper-expression was also observed in the islets of T1D vs. non-diabetic donors, and islet-infiltrating CD8+ T-cells from T1D donors were reactive to some HLA-B-restricted granule peptides. Thus, the inflammatory milieu of insulitis may skew the autoimmune response toward epitopes presented by HLA-B, hence recruiting a distinct T-cell repertoire that may be relevant to T1D pathogenesis.
HostingRepository	PRIDE
AnnounceDate	2025-01-08
AnnouncementXML	Submission_2025-01-08_00:58:16.425.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD045265
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Nicola Ternette
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	L-methionine sulfone; acetylated residue; L-cysteine glutathione disulfide; deamidated residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2023-09-11 05:46:12	ID requested
⏵ 1	2025-01-08 00:58:16	announced

10.1038/S41467-025-55908-9;

10.6019/PXD045265;

submitter keyword: beta cells,HLA-peptidome, interferon-alpha, type 1 diabetes

Nicola Ternette
contact affiliation	University of Oxford
contact email	nicola.ternette@ndm.ox.ac.uk
lab head
Nicola Ternette
contact affiliation	University of Oxford
contact email	nicola.ternette@ndm.ox.ac.uk
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/2025/01/PXD045265

PRIDE project URI

• PRIDE
  1. PXD045265
     1. Label: PRIDE project
     2. Name: HLA-peptidome of human beta cells exposed to interferon-alpha