PXD015249

PXD015249 is an original dataset announced via ProteomeXchange.

Title	HLA-DR15 Molecules Jointly Shape an Autoreactive T Cell Repertoire in Multiple Sclerosis
Description	Autoimmune diseases are often associated with HLA molecules. Multiple sclerosis (MS) is a prototypical example with the HLA-DR15 haplotype as strongest genetic factor. How it contributes to MS is not clear, but key to understand this and other autoimmune diseases. Autoreactive CD4+ T cells and proinflammatory B cells are central pathogenetic factors, and since HLA-DR molecules present peptides to CD4+ T cells, we characterized the peptidomes of the two HLA-DR15 allomorphs DR2a and DR2b on B cells. Self-peptides from HLA-DR α- and β-chains themselves are abundantly presented on B cells. We identified autoreactive CD4+ T cell clones, which recognize HLA-DR-derived self-peptides and peptides from the MS-related infectious agents EBV and Akkermansia and the autoantigen RAS guanyl-releasing protein 2. Our data demonstrate how the two MS-associated HLA-DR15 allomorphs function as antigen-presenting structures and source of peptides during peripheral maintenance of autoreactive T cells and activation by MS-associated pathogens.
HostingRepository	PRIDE
AnnounceDate	2020-10-22
AnnouncementXML	Submission_2020-10-27_07:58:53.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Lena Mühlenbruch
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	LTQ Orbitrap XL

Revision	Datetime	Status	ChangeLog Entry
0	2019-08-30 08:03:01	ID requested
1	2020-10-22 05:28:02	announced
⏵ 2	2020-10-27 07:58:54	announced	2020-10-27: Updated publication reference for PubMed record(s): 33091337.

Wang J, Jelcic I, M, ü, hlenbruch L, Haunerdinger V, Toussaint NC, Zhao Y, Cruciani C, Faigle W, Naghavian R, Foege M, Binder TMC, Eiermann T, Opitz L, Fuentes-Font L, Reynolds R, Kwok WW, Nguyen JT, Lee JH, Lutterotti A, M, ü, nz C, Rammensee HG, Hauri-Hohl M, Sospedra M, Stevanovic S, Martin R, HLA-DR15 Molecules Jointly Shape an Autoreactive T Cell Repertoire in Multiple Sclerosis. Cell, 183(5):1264-1281.e20(2020) [pubmed]

submitter keyword: Multiple sclerosis, HLA-DR15 molecules, B cells, immunopeptidome, HLA-DR-derived self-peptides, autoreactive CD4+ T cells, cross-reactivity, HLA cross-restriction

Stefan Stevanović
contact affiliation	1 Department of Immunology, Interfaculty Institute for Cell Biology, Tübingen, Germany 2 German Cancer Consortium (DKTK), DKFZ Partner Site Tübingen, Tübingen, Germany
contact email	stefan.stevanovic@uni-tuebingen.de
lab head
Lena Mühlenbruch
contact affiliation	1 Department of Immunology, Interfaculty Institute for Cell Biology, Tübingen, Germany 2 German Cancer Consortium (DKTK), DKFZ Partner Site Tübingen, Tübingen, Germany
contact email	lena.muehlenbruch1@gmail.com
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/2020/10/PXD015249

PRIDE project URI

• PRIDE
  1. PXD015249
     1. Label: PRIDE project
     2. Name: HLA-DR15 Molecules Jointly Shape an Autoreactive T Cell Repertoire in Multiple Sclerosis