Antigen specificity of clonally enriched CD8+ T cells in multiple sclerosis
Year: 2026
Type: article
Study design: Observational Study
Abstract: CD8+ T cells are the dominant lymphocyte population in multiple sclerosis (MS) lesions where they are highly clonally expanded. The clonal identity, function, and antigen specificity of CD8+ T cells in MS are not well understood. Here we report a comprehensive single-cell RNA-seq and T cell receptor (TCR)-seq analysis of the cerebrospinal fluid (CSF) and blood from a cohort of treatment-naïve MS patients and control participants. A small subset of highly expanded and activated CD8+ T cells were enriched in the CSF in MS that displayed high activation, cytotoxicity and tissue-homing transcriptional profiles. Using a combination of unbiased and targeted antigen discovery approaches, MS-derived CD8+ T cell clonotypes recognizing Epstein-Barr virus (EBV) antigens and multiple novel mimotopes were identified. These findings shed vital insight into the role of CD8+ T cells in MS and pave the way towards disease biomarkers and therapeutic targets.
Source: Nature Immunology
Authors: Fumie Hayashi, Kristen Mittl, Ravi Dandekar, Josiah Gerdts, Ebtesam Hassan, Ryan D. Schubert, Lindsay Oshiro, Rita Loudermilk, Ariele Greenfield, Danillo G. Augusto, Gregory Havton, Shriya Anumarlu, Arhan Surapaneni, Akshaya Ramesh, Edwina Tran, Kanishka Koshal, Kerry Kizer, Joanna Dreux, Alaina K. Cagalingan, Florian Schustek, Lena Flood, Tamson Moore, Lisa L. Kirkemo, Isabelle J. Fisher, Tiffany Cooper, Meagan Harms, Refujia Gomez, Ahmed Abdelhak, Sergio Baranzini, Riley Bove, Stacy Caillier, Richard Cuneo, Jeffrey Gelfand, Ari Green, Joanne Guo, Sasha Gupta, Harkee Halait, Roland G. Henry, Jill A. Hollenbach, Jorge R. Oksenberg, Nico Papinutto, Samuel Pleasure, Adam Renschen, Simone Sacco, Adam Santaniello, Anna Sindalovsky, Claire D. Clelland, Leah Sibener, Bruce A. C. Cree, Stephen L. Hauser, Jill A. Hollenbach, Marvin Gee, Michael R. Wilson, Scott S. Zamvil, Joseph J. Sabatino
Language: English
Subfield: Pathology and Forensic Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $12,690
Funders: National Multiple Sclerosis Society, Uehara Memorial Foundation, Race to Erase MS, Valhalla Foundation, Multiple Sclerosis Society, National Institutes of Health, University of California, San Francisco, Japan Society for the Promotion of Science, National Institute of Allergy and Infectious Diseases, National Institute of Neurological Disorders and Stroke, Office of Extramural Research, National Institutes of Health
Awards: G1637598100, G1718091717, G1818237499, G1892007872, G2366293035, Detection of disease-relevant CD8+ T cells in Multiple Sclerosis, G339845624, A synthetic biosensor of immunologic synapse formation allowing multiplexed T cell antigen discovery for autoimmune neurologic disorders, Single cell RNA-Seq and clonal analysis of CD8+ T cells in MS, The Role of Ikappa-B Kinase and Glycogen Synthase Kinase 3-beta in Axon Degenerat, G5411661651, G6858630702, Disease relevance of CD20 expression on T cells in multiple sclerosis patients, G9000140382, Role of Natural Killer Cell Diversity in Multiple Sclerosis Risk and Disease Course, Characterization of T cells in MOG antibody-associated disease, The landscape of HLA mediated variation in health and immunity
OpenAlex ID: W7128061587