{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T19:05:35Z","timestamp":1788807935972,"version":"build-2803163510"},"reference-count":40,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,6,29]],"date-time":"2025-06-29T00:00:00Z","timestamp":1751155200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"publisher","award":["PNRR\u2010MCNT1\u20102023\u201012376993"],"award-info":[{"award-number":["PNRR\u2010MCNT1\u20102023\u201012376993"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009873","name":"Regione Autonoma della Sardegna","doi-asserted-by":"publisher","award":["PRIN 2022 n: 2022BP837R"],"award-info":[{"award-number":["PRIN 2022 n: 2022BP837R"]}],"id":[{"id":"10.13039\/501100009873","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009873","name":"Regione Autonoma della Sardegna","doi-asserted-by":"publisher","award":["legge regionale 12 22 December 2022 n. 22"],"award-info":[{"award-number":["legge regionale 12 22 December 2022 n. 22"]}],"id":[{"id":"10.13039\/501100009873","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007421","name":"Li Ka Shing Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007421","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100021856","name":"Ministero dell'Universit\u00e0 e della Ricerca","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100021856","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Immunology"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Multiple sclerosis (MS) is a chronic, autoimmune, inflammatory disease of the central nervous system, driven by T\u2010cell mediated immune responses. Studying T\u2010cell receptor (TCR) clonotypes specific to MS in distinct populations can provide insights into disease mechanisms. The Sardinian population, with its unique genetic background resulting from geographical isolation, presents a high\u2010risk cohort for MS research, offering a valuable context for understanding the disease's pathogenesis. We analysed the frequency of unique TCR clonotypes in peripheral blood samples from Sardinian MS patients and healthy controls, focusing on TCR\u03b1 and TCR\u03b2 CDR3 sequences. Clonotypes were functionally annotated for antigen\u2010specific interactions, and hierarchical analysis was performed to identify shared TCR clonotypes between MS patients and healthy controls. A total of 119 TCR\u03b2 and 521 TCR\u03b1 CDR3 clonotypes were significantly more frequent in MS patients compared to healthy controls (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.05). Several TCR\u2010\u03b1 clonotypes, such as CAVLDSNYQLIW (a MAIT cell clonotype targeting the BST2 antigen) and CAVNTGNQFYF (cross\u2010reactive to multiple antigens, including CMV p65 and BST2), were identified as specific to MS. Shared clonotype analysis revealed the involvement of mucosal\u2010associated invariant T (MAIT) cells and invariant natural killer T (iNKT) cells in MS pathogenesis. Notably, HCV\u2010specific TCR\u2010\u03b1 clonotypes (NS3\u2010HCV) were significantly increased in MS patients, suggesting a link between infectious disease\u2010related and autoimmune\u2010related clonotypes. No significant differences were observed for other antigens, such as VP22, p65 and BST2. This study identifies distinct TCR clonotypes associated with MS in the Sardinian population, highlighting the role of MAIT and iNKT cells in the disease's pathogenesis. The findings suggest that HCV\u2010specific TCR repertoires may contribute to the development of MS. These results improve our understanding of T\u2010cell mediated immune mechanisms in MS and offer potential targets for therapeutic intervention, particularly within the Sardinian cohort.\n                  <\/jats:p>","DOI":"10.1111\/imm.70013","type":"journal-article","created":{"date-parts":[[2025,6,29]],"date-time":"2025-06-29T23:00:21Z","timestamp":1751238021000},"page":"468-478","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Distinct T Cell Receptor Clonotypes in the Sardinian Population Highlight the Role of Mucosal\u2010Associated Invariant T Cells and Invariant Natural Killer T Cells in Multiple Sclerosis"],"prefix":"10.1111","volume":"176","author":[{"given":"Jiaxin","family":"Shen","sequence":"first","affiliation":[{"name":"Department of Hematology The First Affiliated Hospital of Shantou University Medical College  Shantou Guangdong People's Republic of China"},{"name":"Department of Biomedical Sciences University of Sassari  Sassari Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena Rita","family":"Simula","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences University of Sassari  Sassari Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yisu","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences University of Sassari  Sassari Italy"},{"name":"Division of Immunology International Institute of Infection and Immunity, Shantou University Medical College  Shantou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gustavo","family":"Sganzerla Martinez","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology &amp; Canadian Centre for Vaccinology Dalhouise University  Halfax Nova Scotia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaofen","family":"Wen","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences University of Sassari  Sassari Italy"},{"name":"Department of Medical Oncology Cancer Hospital of Shantou University Medical College  Shantou Guangdong People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J.","family":"Kelvin","sequence":"additional","affiliation":[{"name":"Division of Immunology International Institute of Infection and Immunity, Shantou University Medical College  Shantou Guangdong China"},{"name":"Department of Microbiology and Immunology &amp; Canadian Centre for Vaccinology Dalhouise University  Halfax Nova Scotia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0566-2049","authenticated-orcid":false,"given":"Leonardo A.","family":"Sechi","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences University of Sassari  Sassari Italy"},{"name":"SC Microbiologia e Virologia Azienda Ospedaliera Universitaria  Sassari Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,6,29]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2009.11.010"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.4528"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/346183a0"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awaa102"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00968703"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.166.12.7579"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.194.5.669"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41579-022-00770-5"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2012-302925"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1177\/1352458517704711"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-017-8656-z"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni835"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature10251"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.396"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tig.2017.09.004"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa073493"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-018-0215-8"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0033972"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2021.103429"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.22366"},{"key":"e_1_2_10_22_1","unstructured":"S.Andrews \u201cFastQC: A Quality Control Tool for High Throughput Sequence Data \u201d2010."},{"key":"e_1_2_10_23_1","volume-title":"Ea\u2010Utils: Command\u2010Line Tools for Processing Biological Sequencing Data","author":"Aronesty E.","year":"2011"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.3364"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1004503"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-319-24277-4"},{"key":"e_1_2_10_27_1","volume-title":"R: A Language and Environment for Statistical Computing","author":"Team R. 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