{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T23:16:45Z","timestamp":1791415005070,"version":"4.3.3"},"reference-count":51,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2014,9,16]],"date-time":"2014-09-16T00:00:00Z","timestamp":1410825600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100006095","name":"South-Eastern Norway Regional Health Authority","doi-asserted-by":"crossref","award":["2010062\/2009"],"award-info":[{"award-number":["2010062\/2009"]}],"id":[{"id":"10.13039\/501100006095","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Eur J Immunol"],"published-print":{"date-parts":[[2014,11]]},"abstract":"<jats:p>Epstein\u2010Barr virus (EBV) has long been suggested as a pathogen in multiple sclerosis (MS). Here, we used high\u2010throughput sequencing to determine the diversity, compartmentalization, persistence, and EBV\u2010reactivity of the T\u2010cell receptor (TCR) repertoires in MS. TCR\u2010\u03b2 genes were sequenced in paired samples of cerebrospinal fluid (CSF) and blood from patients with MS and controls with other inflammatory neurological diseases. The TCR repertoires were highly diverse in both compartments and patient groups. Expanded T\u2010cell clones, represented by TCR\u2010\u03b2 sequences &gt;0.1%, were of different identity in CSF and blood of MS patients, and persisted for more than a year. Reference TCR\u2010\u03b2 libraries generated from peripheral blood T\u00a0cells reactive against autologous EBV\u2010transformed B cells were highly enriched for public EBV\u2010specific sequences and were used to quantify EBV\u2010reactive TCR\u2010\u03b2 sequences in CSF. TCR\u2010\u03b2 sequences of EBV\u2010reactive CD8<jats:sup>+<\/jats:sup> T\u00a0cells, including several public EBV\u2010specific sequences, were intrathecally enriched in MS patients only, whereas those of EBV\u2010reactive CD4<jats:sup>+<\/jats:sup> T\u00a0cells were also enriched in CSF of controls. These data provide evidence for a clonally diverse, yet compartmentalized and persistent, intrathecal T\u2010cell response in MS. The presented strategy links TCR sequence to intrathecal T\u2010cell specificity, demonstrating enrichment of EBV\u2010reactive CD8<jats:sup>+<\/jats:sup> T\u00a0cells in MS.<\/jats:p>","DOI":"10.1002\/eji.201444662","type":"journal-article","created":{"date-parts":[[2014,8,8]],"date-time":"2014-08-08T00:50:46Z","timestamp":1407459046000},"page":"3439-3452","source":"Crossref","is-referenced-by-count":128,"title":["High\u2010throughput sequencing of TCR repertoires in multiple sclerosis reveals intrathecal enrichment of EBV\u2010reactive CD8<sup>+<\/sup> T\u00a0cells"],"prefix":"10.1002","volume":"44","author":[{"given":"Andreas","family":"Lossius","sequence":"first","affiliation":[{"name":"Department of Immunology and Transfusion Medicine Oslo University Hospital Rikshospitalet  Oslo Norway"},{"name":"Department of Neurology Oslo University Hospital Rikshospitalet  Oslo Norway"},{"name":"Institute of Clinical Medicine University of Oslo  Oslo Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorunn N.","family":"Johansen","sequence":"additional","affiliation":[{"name":"Department of Immunology and Transfusion Medicine Oslo University Hospital Rikshospitalet  Oslo Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frode","family":"Vartdal","sequence":"additional","affiliation":[{"name":"Department of Immunology and Transfusion Medicine Oslo University Hospital Rikshospitalet  Oslo Norway"},{"name":"Institute of Clinical Medicine University of Oslo  Oslo Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harlan","family":"Robins","sequence":"additional","affiliation":[{"name":"Fred Hutchinson Cancer Research Center  Seattle WA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benth","family":"J\u016brat\u0117 \u0160altyt\u0117","sequence":"additional","affiliation":[{"name":"Institute of Clinical Medicine University of Oslo  Oslo Norway"},{"name":"H\u00d8KH Research Centre Akershus University Hospital  L\u00f8renskog Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Trygve","family":"Holm\u00f8y","sequence":"additional","affiliation":[{"name":"Institute of Clinical Medicine University of Oslo  Oslo Norway"},{"name":"Department of Neurology Akershus University Hospital  L\u00f8renskog Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johanna","family":"Olweus","sequence":"additional","affiliation":[{"name":"Department of Immunology Institute for Cancer Research Oslo University Hospital Radiumhospitalet  Oslo Norway"},{"name":"K.G. 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