Epitope glycosylation plays a critical role for T cell recognition of type II collagen in collagen-induced arthritis
(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:
https://lup.lub.lu.se/record/1112803
- author
- Corthay, Alexandre ; Bäcklund, Johan LU ; Broddefalk, Johan ; Michaelsson, Erik ; Goldschmidt, Tom J ; Kihlberg, Jan and Holmdahl, Richard
- organization
- publishing date
- 1998
- 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 Inc.
- 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
- 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
- 189d4ab4-ac62-45b8-ae4c-390ff813e2cf (old id 1112803)
- date added to LUP
- 2016-04-01 12:31:32
- date last changed
- 2022-03-29 02:02:50
@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}},
keywords = {{Autoimmunity; Glycosylation; T cell; Collagen; TCR}},
language = {{eng}},
number = {{8}},
pages = {{2580--2590}},
publisher = {{John Wiley & Sons Inc.}},
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}},
doi = {{10.1002/(SICI)1521-4141(199808)28:08<2580::AID-IMMU2580>3.0.CO;2-X}},
volume = {{28}},
year = {{1998}},
}