{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T23:37:18Z","timestamp":1792798638760,"version":"4.5.0"},"reference-count":63,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"23","funder":[{"DOI":"10.13039\/100012832","name":"Okinaka Memorial Institute for Medical Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100012832","id-type":"DOI","asserted-by":"publisher"}]},{"name":"JSPS KAKENHI","award":["JP20K17430"],"award-info":[{"award-number":["JP20K17430"]}]},{"name":"JSPS KAKENHI","award":["JP22K08528"],"award-info":[{"award-number":["JP22K08528"]}]},{"DOI":"10.13039\/100007449","name":"the Takeda Science Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100007449","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100005865","name":"The Mochida Memorial Foundation for Medical and Pharmaceutical Research","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100005865","id-type":"DOI","asserted-by":"crossref"}]},{"name":"The Nakatomi Foundation","id":[{"id":"https:\/\/ror.org\/0196vdc40","id-type":"ROR","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100008667","name":"The SENSHIN Medical Research Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100008667","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Keio Gijuku Fukuzawa Memorial Fund for the Advancement of Education and Research"},{"name":"Keio University Academic Development Funds","id":[{"id":"https:\/\/ror.org\/02kn6nx58","id-type":"ROR","asserted-by":"crossref"}]},{"name":"JKiC Next-generation Project"},{"name":"The Program for the Advancement of Next Generation Research Projects"},{"name":"The Kowa Life Science Foundation, the Japan Rheumatism Foundation","id":[{"id":"https:\/\/ror.org\/04jpf9990","id-type":"ROR","asserted-by":"crossref"}]},{"name":"a research grant from the Astellas Foundation for Research on Metabolic Disorders","id":[{"id":"https:\/\/ror.org\/0523srp42","id-type":"ROR","asserted-by":"crossref"}]},{"name":"the Takahashi Industrial Economic Research Foundation"},{"name":"The Waksman Foundation"}],"content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2026,6,5]]},"abstract":"<jats:p>\n                    Sj\u00f6gren\u2019s disease (SjD) is an autoimmune disorder characterized by lymphocytic infiltration of exocrine glands. Although B cells producing anti-Ro60 autoantibodies are frequently found in salivary gland lesions, the antigen specificity of CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells has remained unclear. Given accumulating evidence for T cell involvement in local autoantibody production, we comprehensively investigated Ro60 reactivity among lesion-infiltrating CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells. Over 200 T cell receptors (TCRs) enriched in salivary glands from Japanese and Caucasian patients with SjD were screened using a TCR reporter system, identifying 13 Ro60-reactive TCRs predominantly expressed in T peripheral helper\/T follicular helper subset, along with human leukocyte antigen alleles linked to SjD susceptibility. Ro60 was efficiently phagocytosed by antigen-presenting cells in the presence of autoantibodies and presented to Ro60-specific T cells, triggering their activation. This suggests that Ro60-specific B and CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells orchestrate a pathological loop in salivary glands. Our study provides the first molecular identification of a major CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cell antigen in systemic autoimmunity and highlights coordinated T-B cell responses against a shared autoantigen.\n                  <\/jats:p>","DOI":"10.1126\/sciadv.aeb2491","type":"journal-article","created":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T17:59:03Z","timestamp":1780509543000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":3,"title":["Identification of a shared antigen linking CD4\n                    <sup>+<\/sup>\n                    T and B cell pathology in Sj\u00f6gren\u2019s disease"],"prefix":"10.1126","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3281-6595","authenticated-orcid":true,"given":"Masaru","family":"Takeshita","sequence":"first","affiliation":[{"name":"Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9927-7936","authenticated-orcid":true,"given":"Jun","family":"Inamo","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan."},{"name":"Division of Rheumatology, University of Colorado School of Medicine, Aurora, CO 80045, USA."},{"name":"Department of Microbiology and Immunology, Keio University School of Medicine, Tokyo, Japan."},{"name":"Laboratory for Human Immunogenetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-8727-6750","authenticated-orcid":true,"given":"Seiki","family":"Wakui","sequence":"additional","affiliation":[{"name":"JSR-Keio University Medical and Chemical Innovation Center (JKiC), JSR Corp., 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryosuke","family":"Nagashima","sequence":"additional","affiliation":[{"name":"JSR-Keio University Medical and Chemical Innovation Center (JKiC), JSR Corp., 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6441-7572","authenticated-orcid":true,"given":"Takahiro","family":"Nishino","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Keio University School of Medicine, Tokyo, Japan."},{"name":"Laboratory for Human Immunogenetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3214-6288","authenticated-orcid":true,"given":"Kazuyuki","family":"Tsunoda","sequence":"additional","affiliation":[{"name":"Department of Dentistry and Oral Surgery, Keio University School of Medicine, Shinjuku-ku, Tokyo 160-8582, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoshi","family":"Usuda","sequence":"additional","affiliation":[{"name":"Department of Dentistry and Oral Surgery, Keio University School of Medicine, Shinjuku-ku, Tokyo 160-8582, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-3514-3102","authenticated-orcid":true,"given":"Hajime","family":"Inokuchi","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan."},{"name":"Department of Microbiology and Immunology, Keio University School of Medicine, Tokyo, Japan."},{"name":"Laboratory for Human Immunogenetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2881-0657","authenticated-orcid":true,"given":"Kazuyoshi","family":"Ishigaki","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Keio University School of Medicine, Tokyo, Japan."},{"name":"Laboratory for Human Immunogenetics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan."},{"name":"Keio University Human Biology-Microbiome-Quantum Research Center (WPI-Bio2Q), Shinjuku-ku, Tokyo, 160-8582, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6275-046X","authenticated-orcid":true,"given":"Takashi","family":"Sasaki","sequence":"additional","affiliation":[{"name":"Center for Supercentenarian Medical Research, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6216-6730","authenticated-orcid":true,"given":"Yuki","family":"Kagoya","sequence":"additional","affiliation":[{"name":"Division of Tumor Immunology, Institute for Advanced Medical Research, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katsuya","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan."},{"name":"Division of Rheumatology, Department of Internal Medicine, NHO Tokyo Medical Center, Meguro-ku, Tokyo 152-8902, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2646-5765","authenticated-orcid":true,"given":"Yuko","family":"Kaneko","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2018.1"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12016-020-08793-7"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.00444"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/1529-0131(199812)41:12<2238::AID-ART20>3.0.CO;2-V"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2249.1999.00778.x"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2019-215862"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1111\/cei.12058"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1080\/08916934.2019.1684475"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaut.2021.102661"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1265792"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2792"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-020-0867-z"},{"key":"e_1_3_2_14_2","first-page":"2092","article-title":"Identification of Ro(SSA) 52 kDa reactive T cells in labial salivary glands from patients with Sj\u00f6gren\u2019s syndrome","volume":"22","author":"Namekawa T.","year":"1995","unstructured":"T. Namekawa, K. Kuroda, T. Kato, K. Yamamoto, H. Murata, T. Sakamaki, K. Nishioka, I. Iwamoto, Y. Saitoh, T. Sumida, Identification of Ro(SSA) 52 kDa reactive T cells in labial salivary glands from patients with Sj\u00f6gren\u2019s syndrome. J. Rheumatol. 22, 2092\u20132099 (1995).","journal-title":"J. Rheumatol."},{"key":"e_1_3_2_15_2","first-page":"485","article-title":"Alpha-amylase functions as a salivary gland\u2013specific self T cell epitope in patients with Sj\u00f6gren\u2019s syndrome","volume":"3","author":"Matsumoto I.","year":"1999","unstructured":"I. Matsumoto, T. Maeda, Y. Takemoto, Y. Hashimoto, F. Kimura, I. Iwamoto, Y. Saito, K. Nishioka, T. Sumida, Alpha-amylase functions as a salivary gland\u2013specific self T cell epitope in patients with Sj\u00f6gren\u2019s syndrome. Int. J. Mol. Med. 3, 485\u2013490 (1999).","journal-title":"Int. J. Mol. Med."},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.135982"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2023.10.024"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1002\/JLB.5MR1020-057RR"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2022.900349"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2020-217646"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.3390\/jcm9072164"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.150.8.3615"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1002\/1529-0131(199805)41:5<927::AID-ART21>3.0.CO;2-R"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.11103"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.12667\/mhc.8.1"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-025-63935-9"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-022-01547-0"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.2337\/db08-0964"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.167799"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.85609"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.178.9.5727"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-022-01578-0"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaut.2018.04.004"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1093\/cei\/uxae102"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1002\/acr2.11785"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2024.08.025"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-023-00970-x"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41584-024-01201-w"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.160964"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature16962"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaut.2022.102888"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-019-0232-6"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.179.11.7932"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.168.11.5876"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2019-216114"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2024.110258"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41584-024-01167-9"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1136\/ard-2024-226226"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.39859"},{"key":"e_1_3_2_50_2","first-page":"3321","article-title":"Establishment of Epstein-Barr virus growth-transformed lymphoblastoid cell lines","author":"Hui-Yuen J.","year":"2011","unstructured":"J. Hui-Yuen, S. McAllister, S. Koganti, E. Hill, S. Bhaduri-McIntosh, Establishment of Epstein-Barr virus growth-transformed lymphoblastoid cell lines. J. Vis. Exp., 3321 (2011).","journal-title":"J. Vis. Exp."},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2014.006"},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2172-9-50"},{"key":"e_1_3_2_53_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-04262-0"},{"key":"e_1_3_2_54_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V96.2.459.014k50_459_466"},{"key":"e_1_3_2_55_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-023-01943-7"},{"key":"e_1_3_2_56_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-023-01767-y"},{"key":"e_1_3_2_57_2","doi-asserted-by":"publisher","DOI":"10.12688\/f1000research.73600.1"},{"key":"e_1_3_2_58_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.05.031"},{"key":"e_1_3_2_59_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-019-0619-0"},{"key":"e_1_3_2_60_2","doi-asserted-by":"publisher","DOI":"10.1088\/1742-5468\/2008\/10\/P10008"},{"key":"e_1_3_2_61_2","doi-asserted-by":"publisher","DOI":"10.12688\/f1000research.22139.1"},{"key":"e_1_3_2_62_2","doi-asserted-by":"publisher","DOI":"10.1093\/molbev\/msw046"},{"key":"e_1_3_2_63_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btu033"},{"key":"e_1_3_2_64_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.3364"}],"container-title":["Science Advances"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/sciadv.aeb2491","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T17:59:42Z","timestamp":1780509582000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/sciadv.aeb2491"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,5]]},"references-count":63,"journal-issue":{"issue":"23","published-print":{"date-parts":[[2026,6,5]]}},"alternative-id":["10.1126\/sciadv.aeb2491"],"URL":"https:\/\/doi.org\/10.1126\/sciadv.aeb2491","relation":{},"ISSN":["2375-2548"],"issn-type":[{"value":"2375-2548","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,5]]},"assertion":[{"value":"2025-08-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-03-20","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-03","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"eaeb2491"}}