2026/02/05 by Fumie Hayashi, Kristen Mittl, Ravi Dandekar +51 · 1 voice
Biochemistry, Genetics and Molecular Biology · Medicine · #Multiple Sclerosis Research Studies #Polyomavirus and related diseases #vaccines and immunoinformatics approaches
paper · doi:10.1038/s41590-025-02412-3
openalex publication_date 2026/02/05 · openalex created_date 2026/02/07 · openalex updated_date 2026/07/28
Abstract CD8 + T cells are the dominant clonally expanded lymphocyte population in multiple sclerosis (MS) lesions but their clonal identity, function and antigen specificity are not well understood. A comprehensive single-cell RNA-sequencing and T cell receptor-sequencing analysis of the cerebrospinal fluid and blood from individuals in the MS and control cohorts revealed a subset of 23 highly expanded and activated CD8 + T cell clonotypes that were enriched predominantly in the cerebrospinal fluid in the MS cohort. Using unbiased and targeted antigen discovery approaches, six CD8 + T cell clonotypes recognizing Epstein–Barr virus (EBV) antigens and multiple novel mimotopes were identified. Although the majority of mimotopes did not elicit functional responses, three of the expanded CD8 + T cell receptors from patients with MS were reactive to EBV. EBV DNA and transcripts were detected in cerebrospinal fluid, including in patients with MS who had highly expanded EBV-specific CD8 + T cells. These findings shed vital insight into the role of CD8 + T cells in MS and support an important role of EBV in MS immunopathology.