Work

Antigen-resolved remodeling of EBV-specific CD8⁺ T cell immunity in multiple sclerosis

Year: 2026

Type: preprint

Abstract: Multiple sclerosis (MS) is strongly linked to Epstein-Barr Virus (EBV) infection, yet how antiviral immunity contributes to disease pathogenesis remains unclear. Here we delineate EBV-specific CD8+ T cell responses at antigen and single cell resolution in treatment-naïve people with MS. This analysis reveals selective expansion of CD8+ T cells directed to EBV-encoded latent antigens, including EBNA3A and EBNA1. These antigen-specific T cells display enhanced cytotoxicity, a distinct T cell receptor repertoire, and upon engagement with autologous EBV-transformed B cells, adopt a type I interferon-dominated transcriptional state. Most importantly, these MS-specific transcriptional signatures exhibit shared genetic architecture with MS susceptibility genes, supported by enrichment in MS GWAS signals and brain-derived eQTL datasets. Our findings reframe EBV-specific immunity in MS as a state of antigen-specific dysregulation, implicating aberrant surveillance of latently infected B cells as a central pathogenic mechanism and propose latent EBV-specific CD8⁺ T cells as targets for therapeutic intervention.

Source: Research Square

DOI: 10.21203/rs.3.rs-9686341/v1

Authors: Corey Smith, Panteha Khaledi, Oyime Poise Aula, Jessica Engel, Yuanhao Yang, Nicholas Blackburn, Matthew Solomon, Chhavi Asthana, Eleanor Sabey, Pauline Crooks, Natasha Stevens, Yi Chao Foong, Xin Lin, Kathryn Burdon, Jianjun Liu, Jacob Gratten, Rajiv Khanna, Bruce Taylor, Yuan Zhou

Institutions: QIMR Berghofer Medical Research Institute, Mater Research, Menzies Institute for Medical Research, Genome Institute of Singapore

Language: English

Topic: Multiple Sclerosis Research Studies

Subfield: Clinical Neurology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: green

OpenAlex ID: W7163041758

Cites: 44

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Related to: 10