{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T00:10:29Z","timestamp":1792714229979,"version":"4.5.0"},"reference-count":35,"publisher":"National Academy of Sciences","issue":"51","license":[{"start":{"date-parts":[[2016,12,8]],"date-time":"2016-12-08T00:00:00Z","timestamp":1481155200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/www.pnas.org\/site\/misc\/userlicense.xhtml"}],"funder":[{"DOI":"10.13039\/100000890","name":"National Multiple Sclerosis Society","doi-asserted-by":"publisher","award":["RG 4768"],"award-info":[{"award-number":["RG 4768"]}],"id":[{"id":"10.13039\/100000890","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000890","name":"National Multiple Sclerosis Society","doi-asserted-by":"publisher","award":["RG 5179 and RG 5180"],"award-info":[{"award-number":["RG 5179 and RG 5180"]}],"id":[{"id":"10.13039\/100000890","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"HHS | NIH | National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["RO1 AI073737"],"award-info":[{"award-number":["RO1 AI073737"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2016,12,20]]},"abstract":"<jats:title>Significance<\/jats:title>\n                  <jats:p>\n                    Neuromyelitis optica (NMO) is a CNS autoimmune demyelinating disease involving aquaporin-4 (AQP4)-specific IgG1, a T-cell\u2013dependent antibody subclass. The role of T cells in NMO is unclear. We evaluated AQP4-specific T cells in WT and AQP4\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice. AQP4 epitopes identified in WT mice were not pathogenic. AQP4 peptide (p) 135\u2013153 and p201\u2013220 elicited robust T-cell responses in AQP4\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    but not WT, mice. T-cell receptor repertoire utilization for these determinants in AQP4\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice was unique. Donor AQP4\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    p135\u2013153- or p201\u2013220-specific Th17 cells entered the CNS of recipient WT mice and induced CNS autoimmunity. Our findings indicate pathogenic AQP4-specific T cells are normally restrained by central tolerance, which could be relevant to understanding the origin of pathogenic T cells in NMO.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1617859114","type":"journal-article","created":{"date-parts":[[2016,12,8]],"date-time":"2016-12-08T22:45:33Z","timestamp":1481237133000},"page":"14781-14786","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":76,"title":["Tolerance checkpoint bypass permits emergence of pathogenic T cells to neuromyelitis optica autoantigen aquaporin-4"],"prefix":"10.1073","volume":"113","author":[{"given":"Sharon A.","family":"Sagan","sequence":"first","affiliation":[{"name":"Department of Neurology, University of California, San Francisco, CA 94143;"},{"name":"Program in Immunology, University of California, San Francisco, CA 94143;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan 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