{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T04:20:25Z","timestamp":1792815625516,"version":"4.5.0"},"reference-count":65,"publisher":"National Academy of Sciences","issue":"39","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2012,9,25]]},"abstract":"<jats:p>\n                    Microscopic polyangiitis is an autoimmune small-vessel vasculitis that often manifests as focal and necrotizing glomerulonephritis and renal failure. Antineutrophil cytoplasmic Abs (ANCAs) specific for myeloperoxidase (MPO) play a role in this disease, but the role of autoreactive MPO-specific CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells is uncertain. By screening overlapping peptides of 20 amino acids spanning the MPO molecule, we identified an immunodominant MPO CD4\n                    <jats:sup>+<\/jats:sup>\n                    T-cell epitope (MPO\n                    <jats:sub>409\u2013428<\/jats:sub>\n                    ). Immunizing C57BL\/6 mice with MPO\n                    <jats:sub>409\u2013428<\/jats:sub>\n                    induced focal necrotizing glomerulonephritis similar to that seen after whole MPO immunization, when MPO was deposited in glomeruli. Transfer of an MPO\n                    <jats:sub>409\u2013428<\/jats:sub>\n                    -specific CD4\n                    <jats:sup>+<\/jats:sup>\n                    T-cell clone to\n                    <jats:italic>Rag<\/jats:italic>\n                    1\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice induced focal necrotizing glomerulonephritis when glomerular MPO deposition was induced either by passive transfer of MPO-ANCA and LPS or by planting MPO\n                    <jats:sub>409\u2013428<\/jats:sub>\n                    conjugated to a murine antiglomerular basement membrane mAb. MPO\n                    <jats:sub>409\u2013428<\/jats:sub>\n                    also induced biologically active anti-MPO Abs in mice. The MPO\n                    <jats:sub>409\u2013428<\/jats:sub>\n                    epitope has a minimum immunogenic core region of 11 amino acids, MPO\n                    <jats:sub>415\u2013426<\/jats:sub>\n                    , with several critical residues. ANCA-activated neutrophils not only induce injury but lodged the autoantigen MPO in glomeruli, allowing autoreactive anti-MPO CD4\n                    <jats:sup>+<\/jats:sup>\n                    cells to induce delayed type hypersensitivity-like necrotizing glomerular lesions. These studies identify an immunodominant MPO T-cell epitope and redefine how effector responses can induce injury in MPO-ANCA\u2013associated microscopic polyangiitis.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1210147109","type":"journal-article","created":{"date-parts":[[2012,9,6]],"date-time":"2012-09-06T20:26:21Z","timestamp":1346963181000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":98,"title":["The immunodominant myeloperoxidase T-cell epitope induces local cell-mediated injury in antimyeloperoxidase glomerulonephritis"],"prefix":"10.1073","volume":"109","author":[{"given":"Joshua D.","family":"Ooi","sequence":"first","affiliation":[{"name":"Center for Inflammatory Diseases, Department of Medicine, Monash University, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janet","family":"Chang","sequence":"additional","affiliation":[{"name":"Center for Inflammatory Diseases, Department of Medicine, Monash University, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J.","family":"Hickey","sequence":"additional","affiliation":[{"name":"Center for Inflammatory Diseases, Department of Medicine, Monash University, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dorin-Bogdan","family":"Borza","sequence":"additional","affiliation":[{"name":"Departments of Medicine and Pathology, Vanderbilt University School of Medicine, Nashville, TN 37232; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars","family":"Fugger","sequence":"additional","affiliation":[{"name":"Medical Research Council Human Immunology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford OX3 9DS, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen R.","family":"Holdsworth","sequence":"additional","affiliation":[{"name":"Center for Inflammatory Diseases, Department of Medicine, Monash University, and"},{"name":"Departments of dNephrology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. 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