1. Antigen-specificity of clonally-enriched CD8+ T cells in multiple sclerosis.
- Author
-
Mittl K, Hayashi F, Dandekar R, Schubert RD, Gerdts J, Oshiro L, Loudermilk R, Greenfield A, Augusto DG, Ramesh A, Tran E, Koshal K, Kizer K, Dreux J, Cagalingan A, Schustek F, Flood L, Moore T, Kirkemo LL, Cooper T, Harms M, Gomez R, Sibener L, Cree BAC, Hauser SL, Hollenbach JA, Gee M, Wilson MR, Zamvil SS, and Sabatino JJ Jr
- 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 CSF-enriched CD8+ T cells were abundant in people with MS and displayed high cytotoxicity and tissue-homing transcriptional profiles. Using a combination of unbiased and targeted antigen discovery approaches, several MS-derived CD8+ T cell clonotypes recognizing Epstein-Barr virus (EBV) antigens and novel mimotopes were identified. These findings shed insight into the functions of CD8+ T cells in MS and may serve as potential disease biomarkers and therapeutic targets., Competing Interests: AR is a current employee of Genentech. JD, AC, FS, LF, TF, LLK, LS, and MG are currently or previously employed by 3T Biosciences. MRW has receives research grant funding from Roche/Genentech and Novartis, has received speaking honoraria from Genentech, Takeda, WebMD and Novartis, and has received licensing fees from CDI Labs. JJS has previously received research grant funding from Roche/Genentech and Novartis and advisory board honoraria from IgM Biosciences. The remaining authors declare no competing interests.
- Published
- 2024
- Full Text
- View/download PDF