Authors
Kjetil Bjornevik, João Vitor Mahler, Philippe A Bilodeau, Brit Ellen Rød, Gabriela Romanow, Takahisa Mikami, Monique Anderson, Natasha Bobrowski-Khoury, Huimin Zhu, James Nguyen, Ying Sun, Marcelo Matiello, David Housman, Bardia Nourbakhsh, Kjell-Morten Myhr, Øivind Torkildsen, Ludvig M Sollid, Michael Levy, Natalia Drosu
Published in
Science translational medicine. Volume 18. Issue 858. Pages eadz6566. Jul 15, 2026. Epub Jul 15, 2026.
Abstract
Multiple sclerosis (MS) pathogenesis is linked to Epstein-Barr virus (EBV), but the underlying immune mechanisms remain unclear. Using an optimized T cell assay, we demonstrate that CD4+ T cells from individuals with MS predominantly target EBV viral particle components, specifically the late lytic capsid and glycoprotein antigens, rather than latent antigens. In contrast, the Epstein-Barr nuclear antigen 1 (EBNA1) primarily activated CD8+ T cells. EBV-specific CD4+ T cell responses were twofold higher in individuals with untreated MS compared with healthy controls, whereas responses to other herpesviruses remained similar. Anti-CD20 therapy initiation in treatment-naïve participants reduced these responses, a finding validated in an independent cohort, and eliminated viral shedding in saliva. Our results establish preferential CD4+ T cell reactivity to EBV late lytic antigens as a key feature of MS, providing a framework for developing EBV-targeted therapies, including vaccines and antivirals.
PMID:
42455903
Bibliographic data and abstract were imported from PubMed on 16 Jul 2026.
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