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Molecular mapping of the Goodpasture's epitope for glomerulonephritis

Bolton, W Kline; Chen, Lanlin; Hellmark, Thomas LU ; Fox, Jay and Wieslander, Jörgen LU (2005) In Transactions of the American Clinical and Climatological Association 116. p.229-238
Abstract
Goodpasture's syndrome is an autoimmune disease characterized by pulmonary hemorrhage, glomerulonephritis, and antiglomerular basement membrane (GBM) antibodies. We have studied a rat model with chimeric proteins (CPs) consisting of portions of the nephritogenic non-collagenous domain of alpha3 type IV collagen (alpha3(IV)NC1) and non-nephritogenic alpha1(IV)NC1. CPs with aminoterminal alpha3 that contains the major epitope for Goodpasture antibody binding induced EAG. We next immunized with D3, an alpha1(IV)NC1 CP with 69AA of alpha3(IV)NC1 (binds Goodpasture sera), D4, the D3 construct shortened by 4 AA (nonbinding), P9 and P10, single AA mutants (nonbinding) and S2, an alpha1(IV)NC1 with nine AA of alpha3(IV)NC1 (binding). GBM, S2 and... (More)
Goodpasture's syndrome is an autoimmune disease characterized by pulmonary hemorrhage, glomerulonephritis, and antiglomerular basement membrane (GBM) antibodies. We have studied a rat model with chimeric proteins (CPs) consisting of portions of the nephritogenic non-collagenous domain of alpha3 type IV collagen (alpha3(IV)NC1) and non-nephritogenic alpha1(IV)NC1. CPs with aminoterminal alpha3 that contains the major epitope for Goodpasture antibody binding induced EAG. We next immunized with D3, an alpha1(IV)NC1 CP with 69AA of alpha3(IV)NC1 (binds Goodpasture sera), D4, the D3 construct shortened by 4 AA (nonbinding), P9 and P10, single AA mutants (nonbinding) and S2, an alpha1(IV)NC1 with nine AA of alpha3(IV)NC1 (binding). GBM, S2 and D3 induced EAG. GBM immunized rats had intense IgG deposits but S2 and D3 rats had minimal deposits. A 13 mer rat peptide encompassing the aminoterminal site induced EAG sans antibody, while peptides not encompassing the region failed to induce GN. Asparagine at position 19 rather than isoleucine was essential for disease induction. These studies define critical limited AA sequences of alpha3(IV)NC1 associated with glomerulonephritis without antibody, and demonstrate that this region contains a T-cell epitope responsible for induction of glomerulonephritis. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Transactions of the American Clinical and Climatological Association
volume
116
pages
229 - 238
publisher
The American Clinical and Climatological Association
external identifiers
  • pmid:16555617
ISSN
0065-7778
language
English
LU publication?
yes
id
2bcd292d-b606-4905-9075-87550d2bb4eb (old id 1134142)
alternative location
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1473157
date added to LUP
2008-06-18 13:48:14
date last changed
2016-11-17 11:24:21
@article{2bcd292d-b606-4905-9075-87550d2bb4eb,
  abstract     = {Goodpasture's syndrome is an autoimmune disease characterized by pulmonary hemorrhage, glomerulonephritis, and antiglomerular basement membrane (GBM) antibodies. We have studied a rat model with chimeric proteins (CPs) consisting of portions of the nephritogenic non-collagenous domain of alpha3 type IV collagen (alpha3(IV)NC1) and non-nephritogenic alpha1(IV)NC1. CPs with aminoterminal alpha3 that contains the major epitope for Goodpasture antibody binding induced EAG. We next immunized with D3, an alpha1(IV)NC1 CP with 69AA of alpha3(IV)NC1 (binds Goodpasture sera), D4, the D3 construct shortened by 4 AA (nonbinding), P9 and P10, single AA mutants (nonbinding) and S2, an alpha1(IV)NC1 with nine AA of alpha3(IV)NC1 (binding). GBM, S2 and D3 induced EAG. GBM immunized rats had intense IgG deposits but S2 and D3 rats had minimal deposits. A 13 mer rat peptide encompassing the aminoterminal site induced EAG sans antibody, while peptides not encompassing the region failed to induce GN. Asparagine at position 19 rather than isoleucine was essential for disease induction. These studies define critical limited AA sequences of alpha3(IV)NC1 associated with glomerulonephritis without antibody, and demonstrate that this region contains a T-cell epitope responsible for induction of glomerulonephritis.},
  author       = {Bolton, W Kline and Chen, Lanlin and Hellmark, Thomas and Fox, Jay and Wieslander, Jörgen},
  issn         = {0065-7778},
  language     = {eng},
  pages        = {229--238},
  publisher    = {The American Clinical and Climatological Association},
  series       = {Transactions of the American Clinical and Climatological Association},
  title        = {Molecular mapping of the Goodpasture's epitope for glomerulonephritis},
  volume       = {116},
  year         = {2005},
}