The major T cell epitope on type II collagen is glycosylated in normal cartilage but modified by arthritis in both rats and humans
(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:
https://lup.lub.lu.se/record/251978
- author
- 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
- organization
- publishing date
- 2005
- 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 & 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
- 2022-03-21 02:01:08
@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}},
keywords = {{arthritis; processing; glycosylation; CII; APC}},
language = {{eng}},
number = {{2}},
pages = {{357--366}},
publisher = {{John Wiley & 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}},
}