Advanced

The major T cell epitope on type II collagen is glycosylated in normal cartilage but modified by arthritis in both rats and humans

Dzhambazov, Balik LU ; Holmdahl, Meirav LU ; Yamada, Hisakata LU ; Lu, Shemin LU ; Vestberg, Mikael LU ; Holm, B ; Johnell, Olof LU ; Kihlberg, J and Holmdahl, Rikard LU (2005) In European Journal of Immunology 35(2). p.357-366
Abstract
Type II collagen (CII) is a target for autoreactive T cells in both rheumatoid arthritis and the murine model collagen-induced arthritis. The determinant core of CII has been identified as CII260-270, and the alteration of this T cell epitope by posttranslational modifications is known to be critical for development of arthritis in mice. Using CII-specific T cell hybridomas we have now shown that the immunodominant T cell epitope in the normal (healthy) human and rat joint cartilage is O-glycosylated at the critical T cell receptor recognition position 264 with a mono- or di-saccharide attached to a hydroxylysine. In contrast, in the arthritic human and rat joint cartilage there are both glycosylated and non-glycosylated CII forms.... (More)
Type II collagen (CII) is a target for autoreactive T cells in both rheumatoid arthritis and the murine model collagen-induced arthritis. The determinant core of CII has been identified as CII260-270, and the alteration of this T cell epitope by posttranslational modifications is known to be critical for development of arthritis in mice. Using CII-specific T cell hybridomas we have now shown that the immunodominant T cell epitope in the normal (healthy) human and rat joint cartilage is O-glycosylated at the critical T cell receptor recognition position 264 with a mono- or di-saccharide attached to a hydroxylysine. In contrast, in the arthritic human and rat joint cartilage there are both glycosylated and non-glycosylated CII forms. Glycosylated CII from normal cartilage could not be recognized by T cells reactive to peptides having only lysine or hydroxylysine at position 264, showing that antigen-presenting cells could not degrade the O-linked carbohydrate. Thus, the variable forms of the glycosylated epitope are determined by the structures present in cartilage, and these vary during the disease course. We conclude that the chondrocyte determines the structures presented to the immune system and that these structures are different in normal versus arthritic states. (Less)
Please use this url to cite or link to this publication:
author
; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
arthritis, processing, glycosylation, CII, APC
in
European Journal of Immunology
volume
35
issue
2
pages
357 - 366
publisher
John Wiley and Sons Inc.
external identifiers
  • pmid:15682451
  • wos:000227187300004
  • scopus:14744303722
ISSN
1521-4141
DOI
10.1002/eji.200425637
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: Department of Experimental Medical Science (013210000), Orthopaedics (013242900), Department of Dermatology and Venereology (Lund) (013006000), Medical Inflammation Research (013212019), Clinical and Molecular Osteoporosis Research Unit (013242930)
id
4396d14c-a458-45d5-9592-37e501e25a92 (old id 251978)
date added to LUP
2016-04-01 12:16:50
date last changed
2020-08-19 03:20:23
@article{4396d14c-a458-45d5-9592-37e501e25a92,
  abstract     = {Type II collagen (CII) is a target for autoreactive T cells in both rheumatoid arthritis and the murine model collagen-induced arthritis. The determinant core of CII has been identified as CII260-270, and the alteration of this T cell epitope by posttranslational modifications is known to be critical for development of arthritis in mice. Using CII-specific T cell hybridomas we have now shown that the immunodominant T cell epitope in the normal (healthy) human and rat joint cartilage is O-glycosylated at the critical T cell receptor recognition position 264 with a mono- or di-saccharide attached to a hydroxylysine. In contrast, in the arthritic human and rat joint cartilage there are both glycosylated and non-glycosylated CII forms. Glycosylated CII from normal cartilage could not be recognized by T cells reactive to peptides having only lysine or hydroxylysine at position 264, showing that antigen-presenting cells could not degrade the O-linked carbohydrate. Thus, the variable forms of the glycosylated epitope are determined by the structures present in cartilage, and these vary during the disease course. We conclude that the chondrocyte determines the structures presented to the immune system and that these structures are different in normal versus arthritic states.},
  author       = {Dzhambazov, Balik and Holmdahl, Meirav and Yamada, Hisakata and Lu, Shemin and Vestberg, Mikael and Holm, B and Johnell, Olof and Kihlberg, J and Holmdahl, Rikard},
  issn         = {1521-4141},
  language     = {eng},
  number       = {2},
  pages        = {357--366},
  publisher    = {John Wiley and Sons Inc.},
  series       = {European Journal of Immunology},
  title        = {The major T cell epitope on type II collagen is glycosylated in normal cartilage but modified by arthritis in both rats and humans},
  url          = {http://dx.doi.org/10.1002/eji.200425637},
  doi          = {10.1002/eji.200425637},
  volume       = {35},
  year         = {2005},
}