2026-01-14 カロリンスカ研究所(KI)
<関連情報>
- https://news.ki.se/new-mechanism-links-epstein-barr-virus-to-ms
- https://www.cell.com/cell/fulltext/S0092-8674(25)01481-3
アノクタミン2特異的T細胞はエプスタイン・バーウイルスと多発性硬化症を関連付ける Anoctamin-2-specific T cells link Epstein-Barr virus to multiple sclerosis
Olivia G. Thomas ∙ Urszula Rykaczewska ∙ Marina Galešić ∙ … ∙ Hans Grönlund ∙ André Ortlieb Guerreiro-Cacais ∙ Tomas Olsson
Cell Published:January 13, 2026
DOI:https://doi.org/10.1016/j.cell.2025.12.032
Graphical abstract
Highlights
- Anoctamin-2 (ANO2) is targeted by T cells in approximately 57% of persons with MS
- EBNA1 and ANO2 T cell responses are cross-reactive in humans and mice
- ANO2 and EBNA1 T cells have overlapping TCR repertoires and pathogenic phenotypes
- ANO2 immunization or ANO2-specific T cell transfer in mice leads to worsened MS-like disease
Summary
Epstein-Barr virus (EBV) infection constitutes a prerequisite for multiple sclerosis (MS) development, and cross-reactivity between EBV nuclear antigen 1 (EBNA1) and anoctamin-2 (ANO2) antibodies was previously demonstrated in persons with MS (pwMS). Here, we show that ANO2-specific CD4+ T cells are more frequent in pwMS. Immunization of SJL/J mice with ANO2 or EBNA1 led to cross-reactive CD4+ T cell and antibody responses. ANO2 pre-immunization led to exacerbated experimental autoimmune encephalomyelitis (EAE), an effect mediated by CD4+ T cells, as confirmed by adoptive transfer experiments. T cell clones with cross-reactivity to EBNA1 and ANO2 could be isolated from natalizumab-treated pwMS, and sequencing of EBNA1- and ANO2-specific T cell receptors (TCRs) revealed a significant repertoire overlap. We thus report the first mechanistic evidence that EBNA1 CD4+ T cells can target the MS autoantigen ANO2, thereby establishing a link between EBV infection and neuroinflammation.
