{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T07:18:23Z","timestamp":1791875903910,"version":"4.3.4"},"reference-count":35,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2017,6,9]],"date-time":"2017-06-09T00:00:00Z","timestamp":1496966400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["HL114669"],"award-info":[{"award-number":["HL114669"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Immunity Inflam &amp;amp; Disease"],"published-print":{"date-parts":[[2017,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>Organ\u2010specific autoimmune diseases are believed to result from immune responses generated against self\u2010antigens specific to each organ. However, when such responses target antigens expressed promiscuously in multiple tissues, then the immune\u2010mediated damage may be wide spread.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In this report, we describe a mitochondrial protein, branched chain \u03b1\u2010ketoacid dehydrogenase kinase (BCKD<jats:sub>k<\/jats:sub>) that can act as a target autoantigen in the development of autoimmune inflammatory reactions in both heart and liver.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We demonstrate that BCKD<jats:sub>k<\/jats:sub> protein contains at least nine immunodominant epitopes, three of which, BCKD<jats:sub>k<\/jats:sub> 71\u201390, BCKD<jats:sub>k<\/jats:sub> 111\u2013130 and BCKD<jats:sub>k<\/jats:sub> 141\u2013160, were found to induce varying degrees of myocarditis in immunized mice. One of these, BCKD<jats:sub>k<\/jats:sub> 111\u2013130, could also induce hepatitis without affecting lungs, kidneys, skeletal muscles, and brain. In immunogenicity testing, all three peptides induced antigen\u2010specific T cell responses, as verified by proliferation assay and\/or major histocompatibility complex class II\/IA<jats:sup>k<\/jats:sup> dextramer staining. Finally, the disease\u2010inducing abilities of BCKD<jats:sub>k<\/jats:sub> peptides were correlated with the production of interferon\u2010\u03b3, and the activated T cells could transfer disease to naive recipients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The disease induced by BCKD<jats:sub>k<\/jats:sub> peptides could serve as a useful model to study the autoimmune events of inflammatory heart and liver diseases.<\/jats:p><\/jats:sec>","DOI":"10.1002\/iid3.177","type":"journal-article","created":{"date-parts":[[2017,6,9]],"date-time":"2017-06-09T08:09:59Z","timestamp":1496995799000},"page":"421-434","source":"Crossref","is-referenced-by-count":14,"title":["Branched chain \u03b1\u2010ketoacid dehydrogenase kinase 111\u2013130, a T cell epitope that induces both autoimmune myocarditis and hepatitis in A\/J mice"],"prefix":"10.1002","volume":"5","author":[{"given":"Bharathi","family":"Krishnan","sequence":"first","affiliation":[{"name":"School of Veterinary Medicine and Biomedical Sciences University of Nebraska\u2010Lincoln Lincoln Nebraska USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chandirasegaran","family":"Massilamany","sequence":"additional","affiliation":[{"name":"School of Veterinary Medicine and Biomedical Sciences University of Nebraska\u2010Lincoln Lincoln Nebraska USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rakesh H.","family":"Basavalingappa","sequence":"additional","affiliation":[{"name":"School of Veterinary Medicine and Biomedical Sciences University of Nebraska\u2010Lincoln Lincoln Nebraska USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arunakumar","family":"Gangaplara","sequence":"additional","affiliation":[{"name":"School of Veterinary Medicine and Biomedical Sciences University of Nebraska\u2010Lincoln Lincoln Nebraska USA"},{"name":"Laboratory of Immunology, National Institute of Allergy and Infectious Diseases National Institutes of Health Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guobin","family":"Kang","sequence":"additional","affiliation":[{"name":"Nebraska Center for Virology, School of Biological Sciences University of Nebraska\u2010Lincoln  Lincoln Nebraska USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingsheng","family":"Li","sequence":"additional","affiliation":[{"name":"Nebraska Center for Virology, School of Biological Sciences University of Nebraska\u2010Lincoln  Lincoln Nebraska USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco A.","family":"Uzal","sequence":"additional","affiliation":[{"name":"School of Veterinary Medicine University of California  Davis California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer L.","family":"Strande","sequence":"additional","affiliation":[{"name":"Department of Medicine, Cell Biology, Neurobiology and Anatomy Medical College of Wisconsin Milwaukee Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gustavo A.","family":"Delhon","sequence":"additional","affiliation":[{"name":"School of Veterinary Medicine and Biomedical Sciences University of Nebraska\u2010Lincoln Lincoln Nebraska USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean\u2010Jack","family":"Riethoven","sequence":"additional","affiliation":[{"name":"Center for Biotechnology University of Nebraska\u2010Lincoln Lincoln Nebraska USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Steffen","sequence":"additional","affiliation":[{"name":"School of Veterinary Medicine and Biomedical Sciences University of Nebraska\u2010Lincoln Lincoln Nebraska USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4082-9254","authenticated-orcid":false,"given":"Jay","family":"Reddy","sequence":"additional","affiliation":[{"name":"School of Veterinary Medicine and Biomedical Sciences University of Nebraska\u2010Lincoln Lincoln Nebraska USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,6,9]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9343(99)80164-8"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2016.08.005"},{"key":"e_1_2_7_4_1","doi-asserted-by":"crossref","first-page":"4754","DOI":"10.4049\/jimmunol.153.10.4754","article-title":"Epitope mapping of the branched chain alpha\u2010ketoacid dehydrogenase dihydrolipoyl transacylase (BCKD\u2010E2) protein that reacts with sera from patients with idiopathic dilated cardiomyopathy","volume":"153","author":"Ansari A. 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