Anoctamin-2-specific T cells link Epstein-Barr virus to multiple sclerosis

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…

• NM
  National Multiple Sclerosis Society
• FE
  Familjen Erling-Perssons Stiftelse
• EC
  European Committee for Treatment and Research in Multiple Sclerosis
• GO
  Gunvor och Josef Anérs Siftelse
• C
  Cancerfonden
• KO
  Knut och Alice Wallenbergs Stiftelse
• V
  Vetenskapsrådet
• FO
  Forskningsrådet om Hälsa, Arbetsliv och Välfärd
• RF
  Radiumhemmets Forskningsfonder
• HE
  HORIZON EUROPE Framework Programme
• HM
  H2020 Marie Skłodowska-Curie Actions
• HE
  HORIZON EUROPE Reforming and enhancing the European Research and Innovation system