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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/226238
- author
- Bolton, W K
; Chen, L L
; Hellmark, Thomas
LU
; Wieslander, Jörgen
LU
and Fox, J W
- organization
- publishing date
- 2005
- 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
- 2016-04-01 16:36:06
- date last changed
- 2022-01-28 20:50:26
@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}},
doi = {{10.1681/ASN.2004100823}},
volume = {{16}},
year = {{2005}},
}