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Glycosylation of type II collagen is of major importance for T cell tolerance and pathology in collagen-induced arthritis.

Bäcklund, Johan LU ; Treschow, Alexandra LU ; Bockermann, Robert LU ; Holm, Björn; Holm, Lotta; Issazadeh-Navikas, Shohreh; Kihlberg, Jan and Holmdahl, Rikard LU (2002) In European Journal of Immunology 32(12). p.3776-3784
Abstract
Type II collagen (CII) is a candidate cartilage-specific autoantigen, which can become post-translationally modified by hydroxylation and glycosylation. T cell recognition of CII is essential for the development of murine collagen-induced arthritis (CIA) and also occurs in rheumatoid arthritis (RA). The common denominator of murine CIA and human RA is the presentation of an immunodominant CII-derived glycosylated peptide on murine Aq and human DR4 molecules, respectively. To investigate the importance of T cell recognition of glycosylated CII in CIA development after immunization with heterologous CII, we treated neonatal mice with different heterologous CII-peptides (non-modified, hydroxylated and galactosylated). Treatment with the... (More)
Type II collagen (CII) is a candidate cartilage-specific autoantigen, which can become post-translationally modified by hydroxylation and glycosylation. T cell recognition of CII is essential for the development of murine collagen-induced arthritis (CIA) and also occurs in rheumatoid arthritis (RA). The common denominator of murine CIA and human RA is the presentation of an immunodominant CII-derived glycosylated peptide on murine Aq and human DR4 molecules, respectively. To investigate the importance of T cell recognition of glycosylated CII in CIA development after immunization with heterologous CII, we treated neonatal mice with different heterologous CII-peptides (non-modified, hydroxylated and galactosylated). Treatment with the galactosylated peptide (galactoseat position 264) was superior in protecting mice from CIA. Protection was accompanied by a reduced antibody response to CII and by an impaired T cell response to the glycopeptide. To investigate the importance of glycopeptide recognition in an autologous CIA model, we treated MMC-transgenic mice, which express the heterologous CII epitope with a glutamic acid in position 266 in cartilage, with CII-peptides. Again, a strong vaccination potential of the glycopeptide was seen. Hence CII-glycopeptides may be the optimal choice of vaccination target in RA, since humans share the same epitope as the MMC mouse (Less)
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organization
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published
subject
keywords
Mice, Male, Immune Tolerance, Human, Glycosylation, Female, Inbred C3H, Non-U.S. Gov't, T-Lymphocytes: immunology, Transgenic, Collagen Type II: genetics, Collagen Type II: chemistry, Autoimmunity, Rheumatoid: immunology, Support, Cross Reactions, Collagen Type II: immunology, Arthritis, Animal, Experimental: immunology, Experimental: metabolism, Experimental: pathology, Rheumatoid: etiology
in
European Journal of Immunology
volume
32
issue
12
pages
3776 - 3784
publisher
John Wiley & Sons
external identifiers
  • wos:000179907000047
  • scopus:0036919338
ISSN
1521-4141
DOI
10.1002/1521-4141(200212)32:12<3776::AID-IMMU3776>3.0.CO;2-A
language
English
LU publication?
yes
id
7b664def-176d-460a-80d8-3436174306b9 (old id 112927)
date added to LUP
2007-06-26 09:14:18
date last changed
2017-11-19 03:35:21
@article{7b664def-176d-460a-80d8-3436174306b9,
  abstract     = {Type II collagen (CII) is a candidate cartilage-specific autoantigen, which can become post-translationally modified by hydroxylation and glycosylation. T cell recognition of CII is essential for the development of murine collagen-induced arthritis (CIA) and also occurs in rheumatoid arthritis (RA). The common denominator of murine CIA and human RA is the presentation of an immunodominant CII-derived glycosylated peptide on murine Aq and human DR4 molecules, respectively. To investigate the importance of T cell recognition of glycosylated CII in CIA development after immunization with heterologous CII, we treated neonatal mice with different heterologous CII-peptides (non-modified, hydroxylated and galactosylated). Treatment with the galactosylated peptide (galactoseat position 264) was superior in protecting mice from CIA. Protection was accompanied by a reduced antibody response to CII and by an impaired T cell response to the glycopeptide. To investigate the importance of glycopeptide recognition in an autologous CIA model, we treated MMC-transgenic mice, which express the heterologous CII epitope with a glutamic acid in position 266 in cartilage, with CII-peptides. Again, a strong vaccination potential of the glycopeptide was seen. Hence CII-glycopeptides may be the optimal choice of vaccination target in RA, since humans share the same epitope as the MMC mouse},
  author       = {Bäcklund, Johan and Treschow, Alexandra and Bockermann, Robert and Holm, Björn and Holm, Lotta and Issazadeh-Navikas, Shohreh and Kihlberg, Jan and Holmdahl, Rikard},
  issn         = {1521-4141},
  keyword      = {Mice,Male,Immune Tolerance,Human,Glycosylation,Female,Inbred C3H,Non-U.S. Gov't,T-Lymphocytes: immunology,Transgenic,Collagen Type II: genetics,Collagen Type II: chemistry,Autoimmunity,Rheumatoid: immunology,Support,Cross Reactions,Collagen Type II: immunology,Arthritis,Animal,Experimental: immunology,Experimental: metabolism,Experimental: pathology,Rheumatoid: etiology},
  language     = {eng},
  number       = {12},
  pages        = {3776--3784},
  publisher    = {John Wiley & Sons},
  series       = {European Journal of Immunology},
  title        = {Glycosylation of type II collagen is of major importance for T cell tolerance and pathology in collagen-induced arthritis.},
  url          = {http://dx.doi.org/10.1002/1521-4141(200212)32:12<3776::AID-IMMU3776>3.0.CO;2-A},
  volume       = {32},
  year         = {2002},
}