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Since anti-E1 antibodies always appear in combination with anti-E2 antibodies, the mechanisms underlying the autoimmunity against E1 may be linked to, but distinct from, those against E2. Here, we demonstrate that intermolecular and intramolecular determinant spreading underlies the autoimmunity against E1. We performed characterizations and epitope mapping for anti-BCOADC-E1 antibodies from both the intermolecular and intramolecular points of view. The antibody reactivities form a cluster against the BCOADC complex that is distinct from that against the PDC complex, and the anti-BCOADC-E1 antibodies arise as part of the cluster against the BCOADC complex. Multiple epitopes are present on the surface of the BCOADC-E1 molecule, and the major epitope overlaps with the active center. Sera with anti-BCOADC-E1 antibodies strongly inhibited the enzyme activity. These findings suggest that the E1 subunit as part of the native BCOADC complex is an immunogen, and that determinant spreading is involved in the pathogenesis of AMA production.<\/jats:p>","DOI":"10.1155\/2012\/369740","type":"journal-article","created":{"date-parts":[[2012,6,21]],"date-time":"2012-06-21T12:06:30Z","timestamp":1340280390000},"page":"1-12","source":"Crossref","is-referenced-by-count":2,"title":["Characterization of Autoantibodies against the E1 Subunit of Branched-Chain 2-Oxoacid Dehydrogenase in Patients with Primary Biliary Cirrhosis"],"prefix":"10.1155","volume":"2012","author":[{"given":"Tsutomu","family":"Mori","sequence":"first","affiliation":[{"name":"Department of Human Lifesciences, Fukushima Medical University School of Nursing, 1 Hikarigaoka, Fukushima 960-1295, 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