{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T23:09:25Z","timestamp":1791587365561,"version":"4.3.4"},"reference-count":28,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2019,2,24]],"date-time":"2019-02-24T00:00:00Z","timestamp":1550966400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81571953"],"award-info":[{"award-number":["81571953"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2019,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Primary biliary cholangitis (<jats:styled-content style=\"fixed-case\">PBC<\/jats:styled-content>) is an organ\u2010specific, T cell\u2010mediated autoimmune disease which is characterized by the breakdown of self\u2010tolerance to the highly conserved pyruvate dehydrogenase complex, especially the pyruvate dehydrogenase E2 complex (<jats:styled-content style=\"fixed-case\">PDC<\/jats:styled-content>\u2010E2). However, the molecular mechanism of breakdown of self\u2010tolerance is still unclear.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A combination of multiplex\u2010<jats:styled-content style=\"fixed-case\">PCR<\/jats:styled-content> and immune repertoire sequencing (<jats:styled-content style=\"fixed-case\">IR<\/jats:styled-content>\u2010seq) was used for a standardized analysis of memory T cell receptor (<jats:styled-content style=\"fixed-case\">TCR<\/jats:styled-content>) \u03b2\u2010chain repertoire of <jats:styled-content style=\"fixed-case\">PBC<\/jats:styled-content> patient and healthy volunteers. In vitro induction and expansion of human <jats:styled-content style=\"fixed-case\">PDC<\/jats:styled-content>\u2010E2<jats:sub>163\u2010176<\/jats:sub> (human <jats:styled-content style=\"fixed-case\">PDC<\/jats:styled-content>\u2010E2)\u2010specific T cells and <jats:italic>E\u00a0coli <\/jats:italic><jats:styled-content style=\"fixed-case\">PDC<\/jats:styled-content>\u2010E2<jats:sub>31\u201044\/134\u2010147\/235\u2010248<\/jats:sub> (<jats:italic>E\u00a0coli <\/jats:italic><jats:styled-content style=\"fixed-case\">PDC<\/jats:styled-content>\u2010E2)\u2010specific T cells, and identified the human (and <jats:italic>E\u00a0coli<\/jats:italic>) <jats:styled-content style=\"fixed-case\">PDC<\/jats:styled-content>\u2010E2\u2010specific <jats:styled-content style=\"fixed-case\">TCR<\/jats:styled-content>\u03b2 repertoire by <jats:styled-content style=\"fixed-case\">IR<\/jats:styled-content>\u2010seq.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Primary biliary cholangitis patients have shorter complementarity\u2010determining region 3s (<jats:styled-content style=\"fixed-case\">CDR<\/jats:styled-content>3s), and higher degree of sequence overlap in the <jats:styled-content style=\"fixed-case\">TCR<\/jats:styled-content>\u03b2 repertoire of memory T cell. Moreover, altered insertion patterns and skewed <jats:styled-content style=\"fixed-case\">TRBV<\/jats:styled-content> segment usage were observed in <jats:styled-content style=\"fixed-case\">PBC<\/jats:styled-content> patients. With regard to the pathogenesis, the concentration of <jats:italic>E\u00a0coli<\/jats:italic> was higher in <jats:styled-content style=\"fixed-case\">PBC<\/jats:styled-content> patients\u2019 faecal. The frequency of <jats:italic>E\u00a0coli<\/jats:italic> (and human)\u2010specific <jats:styled-content style=\"fixed-case\">TCR<\/jats:styled-content>s was higher in the memory <jats:styled-content style=\"fixed-case\">TCR<\/jats:styled-content>\u03b2 repertoire of <jats:styled-content style=\"fixed-case\">PBC<\/jats:styled-content> patients compared with healthy controls. Importantly, the <jats:styled-content style=\"fixed-case\">TCR<\/jats:styled-content>\u03b2 repertoire characteristics were almost identical between <jats:italic>E\u00a0coli <\/jats:italic><jats:styled-content style=\"fixed-case\">PDC<\/jats:styled-content>\u2010E2\u2010related <jats:styled-content style=\"fixed-case\">TCR<\/jats:styled-content>s and human <jats:styled-content style=\"fixed-case\">PDC<\/jats:styled-content>\u2010E2\u2010related <jats:styled-content style=\"fixed-case\">TCR<\/jats:styled-content>s, including the patterns of <jats:styled-content style=\"fixed-case\">TRBV<\/jats:styled-content> usage, <jats:styled-content style=\"fixed-case\">CDR<\/jats:styled-content>3 length and amino acid composition.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our findings comprehensively revealed the <jats:styled-content style=\"fixed-case\">TCR<\/jats:styled-content>\u03b2 repertoire characterization of <jats:styled-content style=\"fixed-case\">PBC<\/jats:styled-content> patients, and provided a <jats:styled-content style=\"fixed-case\">TCR<\/jats:styled-content> molecular basis to understand the mechanism of cross\u2010recognition between human <jats:styled-content style=\"fixed-case\">PDC<\/jats:styled-content>\u2010E2 and <jats:italic>E\u00a0coli <\/jats:italic><jats:styled-content style=\"fixed-case\">PDC<\/jats:styled-content>\u2010E2, and the imbalance of immune tolerance in <jats:styled-content style=\"fixed-case\">PBC<\/jats:styled-content>.<\/jats:p><\/jats:sec>","DOI":"10.1111\/liv.14066","type":"journal-article","created":{"date-parts":[[2019,2,5]],"date-time":"2019-02-05T20:26:53Z","timestamp":1549398413000},"page":"956-966","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["<scp>TCR<\/scp>\u03b2 repertoire of memory T cell reveals potential role for <i>Escherichia coli<\/i> in the pathogenesis of primary biliary 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Diagnosis and Treatment of Infectious Diseases The First Affiliated Hospital, College of Medicine Zhejiang University Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongyu","family":"Jia","sequence":"additional","affiliation":[{"name":"State Key Laboratory for Diagnosis and Treatment of Infectious Diseases Collaborative Innovation center for Diagnosis and Treatment of Infectious Diseases The First Affiliated Hospital, College of Medicine Zhejiang University Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Zeng","sequence":"additional","affiliation":[{"name":"State Key Laboratory for Diagnosis and Treatment of Infectious Diseases Collaborative Innovation center for Diagnosis and Treatment of Infectious Diseases The First Affiliated Hospital, College of Medicine Zhejiang University Hangzhou 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