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- Title
Characterization of the T-cell epitope that causes anti-GBM glomerulonephritis.
- Authors
Robertson, Julie; Wu, Jean; Arends, Jon; Glass II, William; Southwood, Scott; Sette, Alessandro; Ya-Huan Lou
- Abstract
Characterization of the T-cell epitope that causes anti-GBM glomerulonephritis. Background. We have demonstrated that a single T-cell epitope pCol(28-40) (SQTTANPSCPEGT) alone, which is derived from NC1 domain of α3 chain of type IV collagen (Col4α3 NC1), can induce severe glomerulonephritis in Wistar Kyoto rats. This study further characterized this T-cell epitope. Methods. A series of synthetic peptides derived from pCol (28-40) were tested in vivo and in vitro for their T-cell epitope activity and nephritogenicity. Major histocompatability complex (MHC) class II molecules in Wistar Kyoto rats were cloned, and MHC restriction of pCol(28-40) was determined. Results. The T-cell epitope pCol(28-40) was restricted by rat MHC class II RT.1B l. Ten amino acid residues (29 to 38) were mapped to be the minimum core of the T-cell epitope, which was capable of inducing the T-cell response and severe glomerulonephritis. Only three residues were identified as absolutely critical for the T-cell epitope: position 31 (T) was an anchor residue to the class II molecule, and positions 33 (N) and 34 (P) contributed to the specificity of the T-cell epitope. Thus, only substitution at those positions completely abrogated nephritogenicity of the T-cell epitope. Interestingly, pCol (28-40) also bound to human MHC class II human MHC class II molecule HLA-DRB*1501, which has been linked to human anti-glomerular basement membrane (GBM) disease, suggesting that human homologue of pCol(28-40) could be a potential human T-cell epitope. Conclusion. Our study demonstrated that only few residues in the nephritogenic T-cell epitope pCol(28-40) were critical. Our finding also revealed that pCol(28-40) is a potential nephritogenic T-cell epitope in Goodpasture's syndrome.
- Subjects
T cells; LYMPHOCYTES; GLOMERULONEPHRITIS; IMMUNE complex diseases; KIDNEY glomerulus diseases; KIDNEY diseases
- Publication
Kidney International, 2005, Vol 68, Issue 3, p1061
- ISSN
0085-2538
- Publication type
Article
- DOI
10.1111/j.1523-1755.2005.00498.x