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Epitope spreading and autoimmune glomerulonephritis in rats induced by a T cell epitope of Goodpasture's antigen

Bolton, W K; Chen, L L; Hellmark, Thomas LU ; Wieslander, Jörgen LU and Fox, J W (2005) In Journal of the American Society of Nephrology 16(9). p.2657-2666
Abstract
An amino-terminal region of a, chain of type IV collagen noncollagenous domain [alpha(3)(IV)NC1] that induces experimental autoimmune glomerulortephritis (EAG) in rats has been identified. Only recombinant antigens that contain a nine-amino acid (AA) span of alpha(3)(IV)NC1, consistent with a T cell epitope, could induce EAG. It was hypothesized that synthetic peptides of this region should induce EAG. Human and rat peptides of this region were synthesized and rats were immunized to define the nephritogenic epitope. A 13-AA rat peptide induced EAG with proteinuria, decreased renal function, and glomerular basement membrane (GBM)-bound deposits in half of the rats. This peptide induces lymph node cell proliferation and development of... (More)
An amino-terminal region of a, chain of type IV collagen noncollagenous domain [alpha(3)(IV)NC1] that induces experimental autoimmune glomerulortephritis (EAG) in rats has been identified. Only recombinant antigens that contain a nine-amino acid (AA) span of alpha(3)(IV)NC1, consistent with a T cell epitope, could induce EAG. It was hypothesized that synthetic peptides of this region should induce EAG. Human and rat peptides of this region were synthesized and rats were immunized to define the nephritogenic epitope. A 13-AA rat peptide induced EAG with proteinuria, decreased renal function, and glomerular basement membrane (GBM)-bound deposits in half of the rats. This peptide induces lymph node cell proliferation and development of antibodies to epitopes of alpha(3)(IV)NC1 external to the peptide immunogen. Carboxy-terminal extension to 21 amino acids results in all rats' demonstrating anti-GBM antibody and severe EAG. Asparagine at position 19 is critical for EAG induction. None of the 50 rats that were immunized with peptide that contained human sequence with isoleucine at position 19 developed EAG, whereas rat sequence with asparagine 19 induced EAG. Truncation of amino terminal AA of the peptide aborts EAG induction. These studies demonstrate that a T cell epitope of alpha(3)(IV)NC1 induces lymph node cell proliferation, EAG, and intramolecular epitope spreading; that the length of this peptide influences the formation of anti-GBM antibody; and that the presence of asparagine at position 19 of the peptide is critical to disease induction. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of the American Society of Nephrology
volume
16
issue
9
pages
2657 - 2666
publisher
American Society of Nephrology
external identifiers
  • pmid:16049074
  • wos:000231543100017
  • scopus:33344469761
ISSN
1046-6673
DOI
10.1681/ASN.2004100823
language
English
LU publication?
yes
id
236835ab-d68d-4b4f-94f5-77f1d2e4d35b (old id 226238)
date added to LUP
2007-08-10 11:01:35
date last changed
2017-09-03 04:38:33
@article{236835ab-d68d-4b4f-94f5-77f1d2e4d35b,
  abstract     = {An amino-terminal region of a, chain of type IV collagen noncollagenous domain [alpha(3)(IV)NC1] that induces experimental autoimmune glomerulortephritis (EAG) in rats has been identified. Only recombinant antigens that contain a nine-amino acid (AA) span of alpha(3)(IV)NC1, consistent with a T cell epitope, could induce EAG. It was hypothesized that synthetic peptides of this region should induce EAG. Human and rat peptides of this region were synthesized and rats were immunized to define the nephritogenic epitope. A 13-AA rat peptide induced EAG with proteinuria, decreased renal function, and glomerular basement membrane (GBM)-bound deposits in half of the rats. This peptide induces lymph node cell proliferation and development of antibodies to epitopes of alpha(3)(IV)NC1 external to the peptide immunogen. Carboxy-terminal extension to 21 amino acids results in all rats' demonstrating anti-GBM antibody and severe EAG. Asparagine at position 19 is critical for EAG induction. None of the 50 rats that were immunized with peptide that contained human sequence with isoleucine at position 19 developed EAG, whereas rat sequence with asparagine 19 induced EAG. Truncation of amino terminal AA of the peptide aborts EAG induction. These studies demonstrate that a T cell epitope of alpha(3)(IV)NC1 induces lymph node cell proliferation, EAG, and intramolecular epitope spreading; that the length of this peptide influences the formation of anti-GBM antibody; and that the presence of asparagine at position 19 of the peptide is critical to disease induction.},
  author       = {Bolton, W K and Chen, L L and Hellmark, Thomas and Wieslander, Jörgen and Fox, J W},
  issn         = {1046-6673},
  language     = {eng},
  number       = {9},
  pages        = {2657--2666},
  publisher    = {American Society of Nephrology},
  series       = {Journal of the American Society of Nephrology},
  title        = {Epitope spreading and autoimmune glomerulonephritis in rats induced by a T cell epitope of Goodpasture's antigen},
  url          = {http://dx.doi.org/10.1681/ASN.2004100823},
  volume       = {16},
  year         = {2005},
}