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dc.contributor.author
Jelcic, Ivan
dc.contributor.author
Al Nimer, Faiez
dc.contributor.author
Wang, Jian
dc.contributor.author
Lentsch, Verena
dc.contributor.author
Planas, Raquel
dc.contributor.author
Jelcic, Ilijas
dc.contributor.author
Madjovski, Aleksandar
dc.contributor.author
Ruhrmann, Sabrina
dc.contributor.author
Faigle, Wolfgang
dc.contributor.author
Frauenknecht, Katrin
dc.contributor.author
Pinilla, Clemencia
dc.contributor.author
Santos, Radleigh
dc.contributor.author
Hammer, Christian
dc.contributor.author
Ortiz, Yaneth
dc.contributor.author
Opitz, Lennart
dc.contributor.author
Gronlund, Hans
dc.contributor.author
Rogler, Gerhard
dc.contributor.author
Boyman, Onur
dc.contributor.author
Reynolds, Richard
dc.contributor.author
Lutterotti, Andreas
dc.contributor.author
Mohsen, Khademi
dc.contributor.author
Olsson, Tomas
dc.contributor.author
Piehl, Fredrik
dc.contributor.author
Sospedra, Mireia
dc.contributor.author
Martin, Roland
dc.date.accessioned
2018-10-15T13:13:53Z
dc.date.available
2018-10-12T14:42:55Z
dc.date.available
2018-10-15T13:13:53Z
dc.date.issued
2018-09-20
dc.identifier.issn
0092-8674
dc.identifier.issn
1097-4172
dc.identifier.other
10.1016/j.cell.2018.08.011
en_US
dc.identifier.uri
http://hdl.handle.net/20.500.11850/295467
dc.identifier.doi
10.3929/ethz-b-000295467
dc.description.abstract
Multiple sclerosis is an autoimmune disease that is caused by the interplay of genetic, particularly the HLA-DR15 haplotype, and environmental risk factors. How these etiologic factors contribute to generating an autoreactive CD4+ T cell repertoire is not clear. Here, we demonstrate that self-reactivity, defined as “autoproliferation” of peripheral Th1 cells, is elevated in patients carrying the HLA-DR15 haplotype. Autoproliferation is mediated by memory B cells in a HLA-DR-dependent manner. Depletion of B cells in vitro and therapeutically in vivo by anti-CD20 effectively reduces T cell autoproliferation. T cell receptor deep sequencing showed that in vitro autoproliferating T cells are enriched for brain-homing T cells. Using an unbiased epitope discovery approach, we identified RASGRP2 as target autoantigen that is expressed in the brain and B cells. These findings will be instrumental to address important questions regarding pathogenic B-T cell interactions in multiple sclerosis and possibly also to develop novel therapies.
en_US
dc.language.iso
en
en_US
dc.publisher
Cell Press
en_US
dc.rights.uri
http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subject
multiple sclerosis
en_US
dc.subject
B cells
en_US
dc.subject
T cells
en_US
dc.subject
pathogenesis
en_US
dc.subject
HLA-DR15
en_US
dc.subject
autoproliferation
en_US
dc.subject
brain
en_US
dc.subject
T cell receptor
en_US
dc.subject
RASGRP2
en_US
dc.title
Memory B Cells Activate Brain-Homing, Autoreactive CD4(+) T Cells in Multiple Sclerosis
en_US
dc.type
Journal Article
dc.rights.license
Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
dc.date.published
2018-09-20
ethz.journal.title
Cell
ethz.journal.volume
175
en_US
ethz.journal.issue
1
en_US
ethz.journal.abbreviated
Cell
ethz.pages.start
85
en_US
ethz.pages.end
100.e23
en_US
ethz.version.deposit
publishedVersion
en_US
ethz.identifier.wos
ethz.identifier.scopus
ethz.publication.place
Cambridge, MA
en_US
ethz.publication.status
published
en_US
ethz.leitzahl
ETH Zürich::00002 - ETH Zürich::00003 - Schulleitung und Dienste::00022 - Bereich VP Forschung & Wirtschaftsbez. / Domain VP Research & Corporate Relations::02207 - Functional Genomics Center Zürich / Functional Genomics Center Zürich
ethz.leitzahl.certified
ETH Zürich::00002 - ETH Zürich::00003 - Schulleitung und Dienste::00022 - Bereich VP Forschung & Wirtschaftsbez. / Domain VP Research & Corporate Relations::02207 - Functional Genomics Center Zürich / Functional Genomics Center Zürich
ethz.date.deposited
2018-10-12T14:43:16Z
ethz.source
WOS
ethz.eth
yes
en_US
ethz.availability
Open access
en_US
ethz.rosetta.installDate
2018-10-15T13:14:14Z
ethz.rosetta.lastUpdated
2019-02-03T08:20:09Z
ethz.rosetta.exportRequired
true
ethz.rosetta.versionExported
true
ethz.COinS
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