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Glycopeptide specificity of helper T cells obtained in mouse models for rheumatoid arthritis

Holm, B ; Bäcklund, Johan LU ; Recio, MAF ; Holmdahl, Rikard LU and Kihlberg, J (2002) In ChemBioChem 3(12). p.1209-1222
Abstract
Five protected analogues of beta-D-galctosyl-(5R)-5-hydroxy-L-lysine were prepared, in which the galactosyl moiety was modified by monodeoxygenation or inversion of stereochemistry at C-4. The building blocks were used in the solid-phase synthesis of a set of glycopeptides related to the peptide fragment CII256-273 from type II collagen. Evaluation of the glycopeptides revealed that T-cell hybridomas obtained in collagen-induced arthiritis (CIA), which is a common mouse model for rheumatoid arthritis, recognized the galactosyl moiety with high specificity for individual hydroxy groups. Moreover, T-cell hybridomas obtained in a humanized variant of CIA were also found to recognize the glycopeptides in an equally carbohydrate-specific... (More)
Five protected analogues of beta-D-galctosyl-(5R)-5-hydroxy-L-lysine were prepared, in which the galactosyl moiety was modified by monodeoxygenation or inversion of stereochemistry at C-4. The building blocks were used in the solid-phase synthesis of a set of glycopeptides related to the peptide fragment CII256-273 from type II collagen. Evaluation of the glycopeptides revealed that T-cell hybridomas obtained in collagen-induced arthiritis (CIA), which is a common mouse model for rheumatoid arthritis, recognized the galactosyl moiety with high specificity for individual hydroxy groups. Moreover, T-cell hybridomas obtained in a humanized variant of CIA were also found to recognize the glycopeptides in an equally carbohydrate-specific manner. The results allowed the generation of models of the complexes formed between the appropriate class II major histocompatibilty complex (MHC) molecule, glycopeptide, and the T-cell receptor, that is, of an interaction that is critical for the stimulation of T cells in the arthiritis models. In the structural models, peptide side chains anchor the glycopeptide in pockets in the class II MHC molecule, whereas the galactosylated hydroxylisine residue forms the key contacts with the T-cell receptor. Importantly, the results also suggest that a T-cell response towards glycopeptide fragments from type II collagen could play an important role in the development of rheumatoid arthiritis in humans. (Less)
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author
; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
solid phase synthesis, rheumatoid arthritis, molecular recognition, glycopeptides, immunology
in
ChemBioChem
volume
3
issue
12
pages
1209 - 1222
publisher
John Wiley and Sons
external identifiers
  • wos:000179673300005
  • pmid:12465029
  • scopus:12244254502
ISSN
1439-4227
DOI
10.1002/1439-7633(20021202)3:12<1209::AID-CBIC1209>3.0.CO;2-0
language
English
LU publication?
yes
additional info
The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Medical Inflammation Research (013212019)
id
0a5d9315-26f4-4817-a170-cc970adaa9b8 (old id 321835)
date added to LUP
2016-04-01 11:57:54
date last changed
2021-01-06 05:37:01
@article{0a5d9315-26f4-4817-a170-cc970adaa9b8,
  abstract     = {Five protected analogues of beta-D-galctosyl-(5R)-5-hydroxy-L-lysine were prepared, in which the galactosyl moiety was modified by monodeoxygenation or inversion of stereochemistry at C-4. The building blocks were used in the solid-phase synthesis of a set of glycopeptides related to the peptide fragment CII256-273 from type II collagen. Evaluation of the glycopeptides revealed that T-cell hybridomas obtained in collagen-induced arthiritis (CIA), which is a common mouse model for rheumatoid arthritis, recognized the galactosyl moiety with high specificity for individual hydroxy groups. Moreover, T-cell hybridomas obtained in a humanized variant of CIA were also found to recognize the glycopeptides in an equally carbohydrate-specific manner. The results allowed the generation of models of the complexes formed between the appropriate class II major histocompatibilty complex (MHC) molecule, glycopeptide, and the T-cell receptor, that is, of an interaction that is critical for the stimulation of T cells in the arthiritis models. In the structural models, peptide side chains anchor the glycopeptide in pockets in the class II MHC molecule, whereas the galactosylated hydroxylisine residue forms the key contacts with the T-cell receptor. Importantly, the results also suggest that a T-cell response towards glycopeptide fragments from type II collagen could play an important role in the development of rheumatoid arthiritis in humans.},
  author       = {Holm, B and Bäcklund, Johan and Recio, MAF and Holmdahl, Rikard and Kihlberg, J},
  issn         = {1439-4227},
  language     = {eng},
  number       = {12},
  pages        = {1209--1222},
  publisher    = {John Wiley and Sons},
  series       = {ChemBioChem},
  title        = {Glycopeptide specificity of helper T cells obtained in mouse models for rheumatoid arthritis},
  url          = {http://dx.doi.org/10.1002/1439-7633(20021202)3:12<1209::AID-CBIC1209>3.0.CO;2-0},
  doi          = {10.1002/1439-7633(20021202)3:12<1209::AID-CBIC1209>3.0.CO;2-0},
  volume       = {3},
  year         = {2002},
}