Broader Epstein-Barr virus-specific T cell receptor repertoire in patients with multiple sclerosis

Schneider-Hohendorf, Tilman; Gerdes, Lisa Ann; Pignolet, Beatrice; Gittelman, Rachel; Ostkamp, Patrick; Rubelt, Florian; Raposo, Catarina; Tackenberg, Bjoern; Riepenhausen, Marianne; Janoschka, Claudia; Wuensch, Christian; Bucciarelli, Florence; Flierl-Hecht, Andrea; Beltran, Eduardo; Kuempfel, Tania; Anslinger, Katja; Gross, Catharina C.; Chapman, Heidi; Kaplan, Ian; Brassat, David; Wekerle, Hartmut; Kerschensteiner, Martin; Klotz, Luisa; Luenemann, Jan D.; Hohlfeld, Reinhard; Liblau, Roland; Wiendl, Heinz und Schwab, Nicholas (2022): Broader Epstein-Barr virus-specific T cell receptor repertoire in patients with multiple sclerosis. In: Journal of Experimental Medicine, Bd. 219, Nr. 11, e20220650

Abstract

The EBV-specific T cell receptor repertoire is broader in multiple sclerosis patients, even in diseased siblings of discordant monozygotic twin pairs, indicating an ongoing immune response to Epstein-Barr virus in multiple sclerosis patients, which might hold clues for multiple sclerosis pathogenesis and future therapeutic or preventive avenues. 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 beta chain (TCR beta) repertoires of 1,395 MS patients, 887 controls, and 35 monozygotic, MS-discordant twin pairs for multimer-confirmed, viral antigen-specific TCR beta sequences. We detected more MHC-I-restricted EBV-specific TCR beta 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 beta- 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.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin ; Medizin > Munich Cluster for Systems Neurology (SyNergy)
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 0022-1007
• Sprache: Englisch
• DFG: Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 390857198