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Epitope glycosylation plays a critical role for T cell recognition of type II collagen in collagen-induced arthritis

Corthay, Alexandre; Bäcklund, Johan LU ; Broddefalk, Johan; Michaelsson, Erik; Goldschmidt, Tom J; Kihlberg, Jan and Holmdahl, Richard (1998) In European Journal of Immunology 28(8). p.2580-2590
Abstract
Immunization of mice with type II collagen (CII) leads to collagen-induced arthritis (CIA), a model for rheumatoid arthritis. T cell recognition of CII is believed to be a critical step in CIA development. We have analyzed the T cell determinants on CII and the TCR used for their recognition, using twenty-nine T cell hybridomas derived from C3H.Q and DBA/1 mice immunized with rat CII. All hybridomas were specific for the CII(256-270) segment. However, posttranslational modifications (hydroxylation and variable O-linked glycosylation) of the lysine at position 264 generated five T cell determinants that were specifically recognized by different T cell hybridoma subsets. TCR sequencing indicated that each of the five T cell epitopes selected... (More)
Immunization of mice with type II collagen (CII) leads to collagen-induced arthritis (CIA), a model for rheumatoid arthritis. T cell recognition of CII is believed to be a critical step in CIA development. We have analyzed the T cell determinants on CII and the TCR used for their recognition, using twenty-nine T cell hybridomas derived from C3H.Q and DBA/1 mice immunized with rat CII. All hybridomas were specific for the CII(256-270) segment. However, posttranslational modifications (hydroxylation and variable O-linked glycosylation) of the lysine at position 264 generated five T cell determinants that were specifically recognized by different T cell hybridoma subsets. TCR sequencing indicated that each of the five T cell epitopes selected its own TCR repertoire. The physiological relevance of this observation was shown by in vivo antibody-driven depletion of TCR Valpha2-positive T cells, which resulted in an inhibition of the T cell proliferative response in vitro towards the non-modified CII(256-270), but not towards the glycosylated epitope. Most hybridomas (20/29) specifically recognized CII(256-270) glycosylated with a monosaccharide (beta-D-galactopyranose). We conclude that this glycopeptide is immunodominant in CIA and that posttranslational modifications of CII create new T cell determinants that generate a diverse TCR repertoire. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Autoimmunity, Glycosylation, T cell, Collagen, TCR
in
European Journal of Immunology
volume
28
issue
8
pages
2580 - 2590
publisher
John Wiley & Sons
external identifiers
  • pmid:9710235
  • scopus:0031903794
ISSN
1521-4141
DOI
10.1002/(SICI)1521-4141(199808)28:08<2580::AID-IMMU2580>3.0.CO;2-X
language
English
LU publication?
yes
id
189d4ab4-ac62-45b8-ae4c-390ff813e2cf (old id 1112803)
date added to LUP
2008-07-11 11:22:39
date last changed
2017-10-22 03:55:18
@article{189d4ab4-ac62-45b8-ae4c-390ff813e2cf,
  abstract     = {Immunization of mice with type II collagen (CII) leads to collagen-induced arthritis (CIA), a model for rheumatoid arthritis. T cell recognition of CII is believed to be a critical step in CIA development. We have analyzed the T cell determinants on CII and the TCR used for their recognition, using twenty-nine T cell hybridomas derived from C3H.Q and DBA/1 mice immunized with rat CII. All hybridomas were specific for the CII(256-270) segment. However, posttranslational modifications (hydroxylation and variable O-linked glycosylation) of the lysine at position 264 generated five T cell determinants that were specifically recognized by different T cell hybridoma subsets. TCR sequencing indicated that each of the five T cell epitopes selected its own TCR repertoire. The physiological relevance of this observation was shown by in vivo antibody-driven depletion of TCR Valpha2-positive T cells, which resulted in an inhibition of the T cell proliferative response in vitro towards the non-modified CII(256-270), but not towards the glycosylated epitope. Most hybridomas (20/29) specifically recognized CII(256-270) glycosylated with a monosaccharide (beta-D-galactopyranose). We conclude that this glycopeptide is immunodominant in CIA and that posttranslational modifications of CII create new T cell determinants that generate a diverse TCR repertoire.},
  author       = {Corthay, Alexandre and Bäcklund, Johan and Broddefalk, Johan and Michaelsson, Erik and Goldschmidt, Tom J and Kihlberg, Jan and Holmdahl, Richard},
  issn         = {1521-4141},
  keyword      = {Autoimmunity,Glycosylation,T cell,Collagen,TCR},
  language     = {eng},
  number       = {8},
  pages        = {2580--2590},
  publisher    = {John Wiley & Sons},
  series       = {European Journal of Immunology},
  title        = {Epitope glycosylation plays a critical role for T cell recognition of type II collagen in collagen-induced arthritis},
  url          = {http://dx.doi.org/10.1002/(SICI)1521-4141(199808)28:08<2580::AID-IMMU2580>3.0.CO;2-X},
  volume       = {28},
  year         = {1998},
}