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The pathogenicity of T cell epitopes is not elucidated clearly. In this study, we aim to define the nephritogenic T cell epitopes and its critical amino acid residues. Twenty\u2010four overlapping linear peptides were synthesized covering the whole sequence of human \u03b13(IV)NC1. Wistar\u2013Kyoto rats were immunized with linear peptides, and experimental autoimmune glomerulonephritis was evaluated. Critical amino acid was identified by the loss of nephritogenic function after each amino acid substitution by alanine. Of the 24 peptides, P14 (\u03b13<jats:sub>127\u2010148<\/jats:sub>) could induce 90.5% (19\/21) of WKY rats developing anti\u2010GBM glomerulonephritis with proteinuria, elevated serum urea and creatinine, IgG linear deposit on GBM and substantial (in average 82.4 \u00b1 5.6%) crescent formation in glomeruli. Lymphocytes of immunized rats proliferated in response to \u03b13<jats:sub>127\u2010148<\/jats:sub> and \u03b13(IV)NC1 <jats:italic>in vitro<\/jats:italic>. Sera of these rats recognized \u03b13<jats:sub>127\u2010148<\/jats:sub> and later on together with intact human \u03b13(IV)NC1. Antibodies towards \u03b13<jats:sub>127\u2010148<\/jats:sub> and intact \u03b13(IV)NC1 could also be detected from the kidney elutes. These antibodies showed no cross\u2010reaction with each other, which implies intramolecular epitope spreading during disease progress. After sequential amino acid substitution, the \u03b13<jats:sub>127\u2010148<\/jats:sub> with substitution of tryptophan<jats:sub>136<\/jats:sub>, isoleucine<jats:sub>137<\/jats:sub>, leucine<jats:sub>139<\/jats:sub> or tryptophan<jats:sub>140<\/jats:sub> lost its nephritogenicity. Human \u03b13<jats:sub>127\u2010148<\/jats:sub> is a nephritogenic T cell epitope in WKY rats, with the critical amino acids as W<jats:sub>136<\/jats:sub>I<jats:sub>137<\/jats:sub>xL<jats:sub>139<\/jats:sub>W<jats:sub>140<\/jats:sub>. These findings might facilitate future investigation on microbial aetiology and potential specific immunotherapy of anti\u2010GBM disease.<\/jats:p>","DOI":"10.1111\/jcmm.13134","type":"journal-article","created":{"date-parts":[[2017,3,10]],"date-time":"2017-03-10T15:32:11Z","timestamp":1489159931000},"page":"2117-2128","source":"Crossref","is-referenced-by-count":15,"title":["The pathogenicity of T cell epitopes on human Goodpasture antigen and its critical amino acid motif"],"prefix":"10.1111","volume":"21","author":[{"given":"Shui\u2010yi","family":"Hu","sequence":"first","affiliation":[{"name":"Renal Division Peking University First Hospital Beijing China"},{"name":"Institute of Nephrology Peking University Beijing China"},{"name":"Key Laboratory of Renal Disease Ministry of Health of China Beijing China"},{"name":"Key Laboratory of CKD Prevention and Treatment Ministry of Education of China Beijing China"},{"name":"Department of Nephrology Tianjin Medical University General 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China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miao","family":"Wang","sequence":"additional","affiliation":[{"name":"Renal Division Peking University First Hospital Beijing China"},{"name":"Institute of Nephrology Peking University Beijing China"},{"name":"Key Laboratory of Renal Disease Ministry of Health of China Beijing China"},{"name":"Key Laboratory of CKD Prevention and Treatment Ministry of Education of China Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao\u2010yu","family":"Jia","sequence":"additional","affiliation":[{"name":"Renal Division Peking University First Hospital Beijing China"},{"name":"Institute of Nephrology Peking University Beijing China"},{"name":"Key Laboratory of Renal Disease Ministry of Health of China Beijing China"},{"name":"Key Laboratory of CKD Prevention and Treatment Ministry of Education of China Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhao","family":"Cui","sequence":"additional","affiliation":[{"name":"Renal Division Peking University First Hospital Beijing China"},{"name":"Institute of Nephrology Peking University Beijing China"},{"name":"Key Laboratory of Renal Disease Ministry of Health of China Beijing China"},{"name":"Key Laboratory of CKD Prevention and Treatment Ministry of Education of China Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming\u2010hui","family":"Zhao","sequence":"additional","affiliation":[{"name":"Renal Division Peking University First Hospital Beijing China"},{"name":"Institute of Nephrology Peking University Beijing China"},{"name":"Key Laboratory of Renal Disease Ministry of Health of China Beijing China"},{"name":"Key Laboratory of CKD Prevention and Treatment Ministry of Education of China Beijing China"},{"name":"Peking\u2010Tsinghua Center for Life Sciences Beijing 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