{"doi":"10.1101/2024.09.07.611010","title":"Antigen specificity of clonally-enriched CD8+ T cells in multiple sclerosis","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.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2024,"id":485236,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9354,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1327796,"name":"Fumie Hayashi","orcid":"0000-0002-7754-3770","position":1,"is_corresponding":false},{"id":246845,"name":"Ravi Dandekar","orcid":"0000-0002-2930-3043","position":2,"is_corresponding":false},{"id":246843,"name":"Ryan Schubert","orcid":"0000-0002-3132-5831","position":3,"is_corresponding":false},{"id":845158,"name":"Josiah Gerdts","orcid":null,"position":4,"is_corresponding":false},{"id":1328260,"name":"Lindsay Oshiro","orcid":null,"position":5,"is_corresponding":false},{"id":235413,"name":"Rita P. 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