TY  - JOUR
AU  - Wang, Jian
AU  - Qiu, Yuhan
AU  - Marti, Zoe
AU  - Li, Fengqi
AU  - Wacker, Marcel
AU  - Oldrati, Pietro
AU  - Mühlenbruch, Lena
AU  - Jin, Linlin
AU  - Zhang, Hongxia
AU  - Xu, Wen
AU  - Li, Tingting
AU  - Roschitzki, Bernd
AU  - Faigle, Wolfgang
AU  - Liu, Yingjun
AU  - Nguyen, Julie T
AU  - Lee, Jar-How
AU  - Haunerdinger, Veronika
AU  - Hauri-Hohl, Mathias
AU  - Momburg, Frank
AU  - Bauer, Jens
AU  - Rammensee, Hans-Georg
AU  - Sospedra, Mireia
AU  - Magliozzi, Roberta
AU  - Reynolds, Richard
AU  - Walz, Juliane
AU  - Martin, Roland
TI  - EBV infection and HLA-DR15 jointly drive multiple sclerosis by myelin peptide presentation.
JO  - Cell
VL  - nn
SN  - 0092-8674
CY  - [Cambridge, Mass.]
PB  - Cell Press
M1  - DKFZ-2026-00122
SP  - nn
PY  - 2026
N1  - epub
AB  - Epstein-Barr virus (EBV) is involved in causing and probably also in perpetuating multiple sclerosis (MS). Among several mechanisms of how EBV may contribute are transcriptome alterations, including changes of antigen processing and preferential presentation of both viral and self-antigens. Here, we report that EBV reprograms the transcriptome and immunopeptidome presented on the MS-associated human leukocyte antigen (HLA)-DR15 molecules of infected B cells. Identical myelin basic protein (MBP) peptides were found to be presented on both EBV-infected B cells and MS brain tissue but not primary B cells and thymic tissue. Peripheral memory and cerebrospinal fluid (CSF)-derived CD4+ T cells of HLA-DR15+ MS patients responded to MBP peptides, MBP(78-90) and/or MBP(83-90), and T cell clones raised with these peptides recognized all MBP peptides ending at amino acid MBP90 in MS brain tissue. Our study provides a new mechanistic link for how the environmental and genetic risk factors, EBV infection and HLA-DR15 haplotype, may contribute jointly to MS.
KW  - B cells (Other)
KW  - Epstein-Barr virus (Other)
KW  - autoreactive CD4(+) T cells (Other)
KW  - brain tissue (Other)
KW  - immunopeptidome (Other)
KW  - multiple sclerosis (Other)
KW  - myelin basic protein peptide (Other)
KW  - thymic tissue (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:41534530
DO  - DOI:10.1016/j.cell.2025.12.046
UR  - https://inrepo02.dkfz.de/record/307665
ER  -