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A nephritogenic peptide induces intermolecular epitope spreading on collagen IV in experimental autoimmune glomerulonephritis

Chen, Lanlin; Hellmark, Thomas LU ; Pedchenko, Vadim; Hudson, Billy G.; Pusey, Charles D.; Fox, Jay W. and Bolton, W. Kline (2006) In Journal of the American Society of Nephrology 17(11). p.3076-3081
Abstract
This group previously identified a peptide p13 of alpha 3(IV)NC1 domain of type IV collagen that induces experimental autoimmune glomerulonephritis (EAG) in rats with generation of antibodies to sites on alpha 3(IV)NC1 external to the peptide as a result of intramolecular epitope spreading. It was hypothesized that intermolecular epitope spreading to other collagen IV chains also was induced. Rats were immunized with nephritogenic peptide that was derived from the amino terminal part of rat alpha 3(IV)NC1 domain, and serum and kidney eluate were examined for antibodies to both native and recombinant NC1 domains of collagen IV. Peptide induced EAG with proteinuria and decreased renal function and glomerular basement membrane IgG deposits.... (More)
This group previously identified a peptide p13 of alpha 3(IV)NC1 domain of type IV collagen that induces experimental autoimmune glomerulonephritis (EAG) in rats with generation of antibodies to sites on alpha 3(IV)NC1 external to the peptide as a result of intramolecular epitope spreading. It was hypothesized that intermolecular epitope spreading to other collagen IV chains also was induced. Rats were immunized with nephritogenic peptide that was derived from the amino terminal part of rat alpha 3(IV)NC1 domain, and serum and kidney eluate were examined for antibodies to both native and recombinant NC1 domains of collagen IV. Peptide induced EAG with proteinuria and decreased renal function and glomerular basement membrane IgG deposits. Sera from these rats were examined by ELISA, which revealed reactivity not only to immunizing peptide but also to human and rat alpha 3(IV)NC1 and to human alpha 4(IV)NC1 domains. Kidney eluate that was depleted of alpha 3(IV)NC1 antibodies still reacted to alpha 4(IV)NC1, and alpha 3(IV)NC1 column-bound antibody reacted with alpha 3(IV)NC1. There was minimal reactivity to other collagen chains. Eluate that was adsorbed to NC1 hexamer from rat glonterular basement membrane lost all reactivity to glomerular constituents, and the eluted antibodies reacted to alpha 3(IV)NC1 and alpha 4(IV)NC1 domains. These studies show that a T cell epitope of alpha 3(IV)NC1 induces EAG, intramolecular epitope spreading along alpha 3(IV)NC1, and intermolecular epitope spreading to alpha 4(IV)NC1 domain with minimal or no reactivity to other collagen chains or glomerular constituents. This is the first demonstration in EAG of intermolecular epitope spreading and identification of the spread epitopes. (Less)
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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of the American Society of Nephrology
volume
17
issue
11
pages
3076 - 3081
publisher
American Society of Nephrology
external identifiers
  • wos:000241912100019
  • scopus:33750691020
ISSN
1046-6673
DOI
10.1681/ASN.2006070688
language
English
LU publication?
yes
id
b8798501-c7bb-4a49-a038-c6755cccb724 (old id 376925)
date added to LUP
2007-10-01 17:47:49
date last changed
2019-03-08 02:47:48
@article{b8798501-c7bb-4a49-a038-c6755cccb724,
  abstract     = {This group previously identified a peptide p13 of alpha 3(IV)NC1 domain of type IV collagen that induces experimental autoimmune glomerulonephritis (EAG) in rats with generation of antibodies to sites on alpha 3(IV)NC1 external to the peptide as a result of intramolecular epitope spreading. It was hypothesized that intermolecular epitope spreading to other collagen IV chains also was induced. Rats were immunized with nephritogenic peptide that was derived from the amino terminal part of rat alpha 3(IV)NC1 domain, and serum and kidney eluate were examined for antibodies to both native and recombinant NC1 domains of collagen IV. Peptide induced EAG with proteinuria and decreased renal function and glomerular basement membrane IgG deposits. Sera from these rats were examined by ELISA, which revealed reactivity not only to immunizing peptide but also to human and rat alpha 3(IV)NC1 and to human alpha 4(IV)NC1 domains. Kidney eluate that was depleted of alpha 3(IV)NC1 antibodies still reacted to alpha 4(IV)NC1, and alpha 3(IV)NC1 column-bound antibody reacted with alpha 3(IV)NC1. There was minimal reactivity to other collagen chains. Eluate that was adsorbed to NC1 hexamer from rat glonterular basement membrane lost all reactivity to glomerular constituents, and the eluted antibodies reacted to alpha 3(IV)NC1 and alpha 4(IV)NC1 domains. These studies show that a T cell epitope of alpha 3(IV)NC1 induces EAG, intramolecular epitope spreading along alpha 3(IV)NC1, and intermolecular epitope spreading to alpha 4(IV)NC1 domain with minimal or no reactivity to other collagen chains or glomerular constituents. This is the first demonstration in EAG of intermolecular epitope spreading and identification of the spread epitopes.},
  author       = {Chen, Lanlin and Hellmark, Thomas and Pedchenko, Vadim and Hudson, Billy G. and Pusey, Charles D. and Fox, Jay W. and Bolton, W. Kline},
  issn         = {1046-6673},
  language     = {eng},
  number       = {11},
  pages        = {3076--3081},
  publisher    = {American Society of Nephrology},
  series       = {Journal of the American Society of Nephrology},
  title        = {A nephritogenic peptide induces intermolecular epitope spreading on collagen IV in experimental autoimmune glomerulonephritis},
  url          = {http://dx.doi.org/10.1681/ASN.2006070688},
  volume       = {17},
  year         = {2006},
}