{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T15:23:30Z","timestamp":1786116210112,"version":"build-2736575974"},"reference-count":81,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T00:00:00Z","timestamp":1785888000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Don Carlo Gnocchi Foundation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Autoreactive lymphocytes are thought to contribute to tissue injury in the pathogenesis of multiple sclerosis (MS). However, reliable biomarkers reflecting myelin-specific immune responses and disease activity remain limited. In HLA-DRB1*15:01-positive individuals, the myelin basic protein (MBP) epitope MBP85\u201399 represents a well-characterized immunodominant target of CD4+ T cells. Using classical spectratyping, we characterized the peripheral T-cell receptor (TCR) \u03b2-chain repertoire reactive to MBP85\u201399 in individuals with MS, according to their HLA-DRB1 haplotypes. Selected rearrangements were further evaluated in cerebrospinal fluid (CSF), cytokine-defined T-cell subsets, and longitudinal samples collected during interferon beta-1a treatment. A restricted set of shared (\u201cpublic\u201d) MBP85\u201399-reactive TCR rearrangements was identified in individuals with MS and differed from the repertoire observed in healthy controls. These TCRs were more frequently detected during periods of active disease than during remission. Two disease-associated public rearrangements were enriched in active MS, whereas one rearrangement was preferentially observed in healthy controls. HLA-DRB1*15:01-restricted MBP85\u201399-specific public TCR signatures were associated with inflammatory disease activity in MS and may help distinguish pathogenic from non-pathogenic autoreactive responses. In a longitudinal sub-cohort (n = 15, ~10-year follow-up), the RSI of the principal disease-associated rearrangement TRBV19\u2013TRBJ2.4 correlated positively with cumulative relapse burden (Spearman \u03c1 = 0.782, p = 0.002), providing preliminary evidence that these TCR signatures reflect long-term inflammatory disease activity. These findings support further validation of antigen-specific TCR profiling as a biomarker strategy in MS using contemporary high-throughput immune repertoire technologies.<\/jats:p>","DOI":"10.3390\/ijms27157034","type":"journal-article","created":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T13:16:29Z","timestamp":1785935789000},"page":"7034","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Dynamics of Myelin-Specific T-Cell Repertoires Mirror Disease Activity and Central Nervous System Trafficking in Multiple Sclerosis"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6608-3388","authenticated-orcid":false,"given":"Gabriele","family":"Di Sante","sequence":"first","affiliation":[{"name":"Department of Medicine and Surgery, Section of Human, Clinical and Forensic Anatomy, University of Perugia, 06123 Perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Assunta","family":"Bianco","sequence":"additional","affiliation":[{"name":"Centro di Ricerca Per la Sclerosi Multipla \u201cAnna Paola Batocchi\u201d, Department of Neuroscience, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy"},{"name":"Multiple Sclerosis Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0447-2297","authenticated-orcid":false,"given":"Matteo","family":"Lucchini","sequence":"additional","affiliation":[{"name":"Centro di Ricerca Per la Sclerosi Multipla \u201cAnna Paola Batocchi\u201d, Department of Neuroscience, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy"},{"name":"Multiple Sclerosis Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1047-4210","authenticated-orcid":false,"given":"Anna Maria","family":"Stabile","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, Section of Human, Clinical and Forensic Anatomy, University of Perugia, 06123 Perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4740-2504","authenticated-orcid":false,"given":"Alessandra","family":"Pistilli","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, Section of Human, Clinical and Forensic Anatomy, University of Perugia, 06123 Perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-7499-2941","authenticated-orcid":false,"given":"Marco","family":"Bisurgi","sequence":"additional","affiliation":[{"name":"Centro di Ricerca Per la Sclerosi Multipla \u201cAnna Paola Batocchi\u201d, Department of Neuroscience, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Cicia","sequence":"additional","affiliation":[{"name":"Centro di Ricerca Per la Sclerosi Multipla \u201cAnna Paola Batocchi\u201d, Department of Neuroscience, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3849-757X","authenticated-orcid":false,"given":"Desir\u00e9e","family":"Bartolini","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, University of Perugia, 06123 Perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5234-8023","authenticated-orcid":false,"given":"Loredana","family":"Ingrosso","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Istituto Superiore di Sanit\u00e0, 00161 Rome, Italy"},{"name":"European Program for Public Health Microbiology Training (EUPHEM), European Centre for Disease Prevention and Control (ECDC), 171 83 Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario","family":"Rende","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, Section of Human, Clinical and Forensic Anatomy, University of Perugia, 06123 Perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Concetta","family":"Geloso","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Section of Human Anatomy, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy"},{"name":"Gemelli Science and Technology Park (GSTeP)-Organoids Research Core Facility, Fondazione Policlinico Agostino Gemelli IRCCS, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6371-7354","authenticated-orcid":false,"given":"Simona","family":"Rolla","sequence":"additional","affiliation":[{"name":"Department of Clinical and Biological Sciences, University of Torino, 10043 Orbassano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7455-4290","authenticated-orcid":false,"given":"Francesco","family":"Ria","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine and Surgery, Section of General Pathology, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7783-114X","authenticated-orcid":false,"given":"Massimiliano","family":"Mirabella","sequence":"additional","affiliation":[{"name":"Centro di Ricerca Per la Sclerosi Multipla \u201cAnna Paola Batocchi\u201d, Department of Neuroscience, Universit\u00e0 Cattolica del Sacro Cuore, 00168 Rome, Italy"},{"name":"Multiple Sclerosis Unit, Fondazione Policlinico Universitario A. 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