苏黎世大学Roland Martin小组取得一项新突破。他们揭示了EBV感染和HLA-DR15通过髓磷脂肽呈递共同驱动多发性硬化。相关论文发表在2026年1月13日出版的《细胞》杂志上。
小组报道EBV对感染B细胞的MS相关人白细胞抗原(HLA)-DR15分子上的转录组和免疫肽球进行了重编程。发现在EBV感染的B细胞和MS脑组织中存在相同的髓鞘碱性蛋白（MBP）肽，但在原代B细胞和胸腺组织中不存在。HLA-DR15+ MS患者的外周记忆和脑脊液（CSF）来源的CD4+ T细胞对MBP肽、MBP（78-90）和/或MBP（83-90）有反应，用这些肽培养的T细胞克隆识别MS脑组织中以MBP90氨基酸结尾的所有MBP肽。他们的研究为环境和遗传风险因素EBV感染和HLA-DR15单倍型如何共同促进MS提供了新的机制联系。
据介绍，Epstein-Barr病毒（EBV）参与导管形成，也可能参与多发性硬化症（MS）的延续。EBV的作用机制包括转录组的改变，包括抗原加工的改变以及病毒抗原和自身抗原的优先呈递。
附：英文原文
Title: EBV infection and HLA-DR15 jointly drive multiple sclerosis by myelin peptide presentation
Author: Jian Wang, Yuhan Qiu, Zoe Marti, Fengqi Li, Marcel Wacker, Pietro Oldrati, Lena Mühlenbruch, Linlin Jin, Hongxia Zhang, Wen Xu, Tingting Li, Bernd Roschitzki, Wolfgang Faigle, Yingjun Liu, Julie T. Nguyen, Jar-How Lee, Veronika Haunerdinger, Mathias Hauri-Hohl, Frank Momburg, Jens Bauer, Hans-Georg Rammensee, Mireia Sospedra, Roberta Magliozzi, Richard Reynolds, Juliane Walz, Roland Martin
Issue&Volume: 2026-01-13
Abstract: Epstein-Barr virus (EBV) is involved in causing and probably also in perpetuating multiple sclerosis (MS). Among several mechanisms of how EBV may contribute are transcriptome alterations, including changes of antigen processing and preferential presentation of both viral and self-antigens. Here, we report that EBV reprograms the transcriptome and immunopeptidome presented on the MS-associated human leukocyte antigen (HLA)-DR15 molecules of infected B cells. Identical myelin basic protein (MBP) peptides were found to be presented on both EBV-infected B cells and MS brain tissue but not primary B cells and thymic tissue. Peripheral memory and cerebrospinal fluid (CSF)-derived CD4+ T cells of HLA-DR15+ MS patients responded to MBP peptides, MBP(78–90) and/or MBP(83–90), and T cell clones raised with these peptides recognized all MBP peptides ending at amino acid MBP90 in MS brain tissue. Our study provides a new mechanistic link for how the environmental and genetic risk factors, EBV infection and HLA-DR15 haplotype, may contribute jointly to MS.
DOI: 10.1016/j.cell.2025.12.046
Source: https://www.cell.com/cell/abstract/S0092-8674(25)01495-3