T-cell epitope of alpha3 chain of type IV collagen induces severe glomerulonephritis.
T-cell epitope of alpha3 chain of type IV collagen induces severe glomerulonephritis.
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DOI：
10.1046/j.1523-1755.2003.00227.x
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发表时间：
2003-10
影响因子：
19.6
通讯作者：
Jean Wu;Jason Borillo;W. Glass;J. Hicks;C. Ou;Y. Lou
中科院分区：
文献类型：
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作者：
Jean Wu;Jason Borillo;W. Glass;J. Hicks;C. Ou;Y. Lou
BACKGROUND Anti-glomerular basement membrane (GBM) glomerulonephritis is among the earliest recognized human autoimmune diseases. However, the etiology of anti-GBM glomerulonephritis remains unclear. We have previously shown that CD4+ T cells, specific to alpha3 NC1 of type IV collagen (Col4alpha3NC1), were able to induce anti-GBM glomerulonephritis in Wistar-Kyoto (WKY) rats. In the present study, we continued to map the nephritogenic T cell epitope in Col4alpha3NC1. METHODS Synthetic peptides, which covered Col4alpha3NC1, were used as immunogens to induce glomerulonephritis in WKY rats. T-cell and B-cell responses to the peptides in the animals were analyzed. RESULTS One potent nephritogenic T-cell epitope, pCol(28-40) (SQTTANPSCPEGT), was identified. A single immunization with pCol(28-40) induced extremely severe glomerulonephritis in all 23 rats. Renal pathology revealed nearly 100% of glomeruli with crescentic lesions or tuft necrosis in 21 animals. pCol(28-40) elicited a T-cell response to the peptide; T cells isolated from rats immunized with recombinant Col4alpha3NC1 reacted with pCol(28-40). pCol(28-40) elicited a peptide specific antibody response, which did not react with polypeptide Col4alpha3NC1 or native GBM. An 11-mer peptide, pCol(a30-40) (Ac-TTANPSCPEGT), was further mapped to be the core of the T-cell epitope in pCol(28-40). As expected, immunization with pCol(a30-40) induced severe glomerulonephritis in 10 out of 19 rats. CONCLUSION Our study not only demonstrated that a single T-cell epitope of Col4alpha3NC1 is sufficient to induce severe glomerulonephritis, but also provides a unique model for studying T-cell-mediated mechanisms in anti-GBM glomerulonephritis pathogenesis.
