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Broader Epstein-Barr virus-specific T cell receptor repertoire in patients with multiple sclerosis. 2022
Tilman Schneider-Hohendorf, and
Lisa Ann Gerdes, and
Béatrice Pignolet, and
Rachel Gittelman, and
Patrick Ostkamp, and
Florian Rubelt, and
Catarina Raposo, and
Björn Tackenberg, and
Marianne Riepenhausen, and
Claudia Janoschka, and
Christian Wünsch, and
Florence Bucciarelli, and
Andrea Flierl-Hecht, and
Eduardo Beltrán, and
Tania Kümpfel, and
Katja Anslinger, and
Catharina C Gross, and
Heidi Chapman, and
Ian Kaplan, and
David Brassat, and
Hartmut Wekerle, and
Martin Kerschensteiner, and
Luisa Klotz, and
Jan D Lünemann, and
Reinhard Hohlfeld, and
Roland Liblau, and
Heinz Wiendl, and
Nicholas Schwab
Department of Neurology with Institute of Translational Neurology, University of Münster, Münster, Germany.
Epstein-Barr virus (EBV) infection precedes multiple sclerosis (MS) pathology and cross-reactive antibodies might link EBV infection to CNS autoimmunity. As an altered anti-EBV T cell reaction was suggested in MS, we queried peripheral blood T cell receptor β chain (TCRβ) repertoires of 1,395 MS patients, 887 controls, and 35 monozygotic, MS-discordant twin pairs for multimer-confirmed, viral antigen-specific TCRβ sequences. We detected more MHC-I-restricted EBV-specific TCRβ sequences in MS patients. Differences in genetics or upbringing could be excluded by validation in monozygotic twin pairs discordant for MS. Anti-VLA-4 treatment amplified this observation, while interferon β- or anti-CD20 treatment did not modulate EBV-specific T cell occurrence. In healthy individuals, EBV-specific CD8+ T cells were of an effector-memory phenotype in peripheral blood and cerebrospinal fluid. In MS patients, cerebrospinal fluid also contained EBV-specific central-memory CD8+ T cells, suggesting recent priming. Therefore, MS is not only preceded by EBV infection, but also associated with broader EBV-specific TCR repertoires, consistent with an ongoing anti-EBV immune reaction in MS.
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