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.

中文翻译：

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多发性硬化症患者中更广泛的 Epstein-Barr 病毒特异性 T 细胞受体库

EB 病毒 (EBV) 感染先于多发性硬化症 (MS) 病理发生，交叉反应抗体可能将 EBV 感染与中枢神经系统自身免疫联系起来。由于多发性硬化症中抗 EBV T 细胞反应发生了改变，我们查询了 1,395 名多发性硬化症患者、887 名对照者和 35 对单卵、多发性硬化症不一致的双胞胎的外周血 T 细胞受体 β 链 (TCRβ) 序列，以了解多聚体确认的病毒感染情况。抗原特异性 TCRβ 序列。我们在 MS 患者中检测到更多 MHC-I 限制性 EBV 特异性 TCRβ 序列。通过对 MS 不一致的同卵双胞胎进行验证，可以排除遗传或教养方面的差异。抗 VLA-4 治疗放大了这一观察结果，而干扰素 β 或抗 CD20 治疗并未调节 EBV 特异性 T 细胞的发生。在健康个体中，外周血和脑脊液中的 EBV 特异性 CD8+ T 细胞具有效应记忆表型。在多发性硬化症患者中，脑脊液中还含有 EBV 特异性中央记忆 CD8+ T 细胞，表明最近发生过启动。因此，MS 不仅先于 EBV 感染，而且还与更广泛的 EBV 特异性 TCR 库相关，这与 MS 中持续的抗 EBV 免疫反应一致。