Predominant selection of T cells specific for the glycosylated collagen type II epitope (263-270) in humanized transgenic mice and in rheumatoid arthritis.
(2002) In Proceedings of the National Academy of Sciences 99(15). p.9960-9965- Abstract
- Rheumatoid arthritis (RA) is associated with certain MHC class II alleles and is characterized by a chronic autoimmune response in the joints. Using transgenic mice expressing human DR4 (DRB1*0401) and human CD4, but lacking endogenous MHC class II, we show that posttranslational glycosylation of type II collagen (CII) influences the level of T cell tolerance to this candidate cartilage-specific autoantigen. In such mice, the expression of human CII resulted in a tolerized murine T cell response to human CII. However, tolerance induction remained incomplete, preferentially deleting responses to the nonmodified CII 263-270 epitope, whereas T cell recognition of a glycosylated variant of this epitope was affected to a lesser degree. A... (More)
- Rheumatoid arthritis (RA) is associated with certain MHC class II alleles and is characterized by a chronic autoimmune response in the joints. Using transgenic mice expressing human DR4 (DRB1*0401) and human CD4, but lacking endogenous MHC class II, we show that posttranslational glycosylation of type II collagen (CII) influences the level of T cell tolerance to this candidate cartilage-specific autoantigen. In such mice, the expression of human CII resulted in a tolerized murine T cell response to human CII. However, tolerance induction remained incomplete, preferentially deleting responses to the nonmodified CII 263-270 epitope, whereas T cell recognition of a glycosylated variant of this epitope was affected to a lesser degree. A similar dominance of T cell responses to CII-glycopeptides was recorded in a cohort of severely affected RA-patients (n = 14). Thus, RA T cells predominantly recognize the immunodominant CII peptide in its glycosylated form and may explain why previously it has been difficult to detect T cell responses to CII in RA patients. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/109597
- author
- Bäcklund, Johan LU ; Carlsén, Stefan LU ; Höger, Torsten ; Holm, Björn ; Fugger, Lars ; Kihlberg, Jan ; Burkhardt, Harald and Holmdahl, Rikard LU
- organization
- publishing date
- 2002
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Proceedings of the National Academy of Sciences
- volume
- 99
- issue
- 15
- pages
- 9960 - 9965
- publisher
- National Academy of Sciences
- external identifiers
-
- wos:000177042400066
- scopus:0037162490
- ISSN
- 1091-6490
- DOI
- 10.1073/pnas.132254199
- 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)
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- c1ef0410-e01c-4cfa-bb75-574682487c1b (old id 109597)
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- http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12089323&dopt=Abstract
- date added to LUP
- 2016-04-01 12:19:29
- date last changed
- 2022-01-27 02:01:48
@article{c1ef0410-e01c-4cfa-bb75-574682487c1b,
abstract = {{Rheumatoid arthritis (RA) is associated with certain MHC class II alleles and is characterized by a chronic autoimmune response in the joints. Using transgenic mice expressing human DR4 (DRB1*0401) and human CD4, but lacking endogenous MHC class II, we show that posttranslational glycosylation of type II collagen (CII) influences the level of T cell tolerance to this candidate cartilage-specific autoantigen. In such mice, the expression of human CII resulted in a tolerized murine T cell response to human CII. However, tolerance induction remained incomplete, preferentially deleting responses to the nonmodified CII 263-270 epitope, whereas T cell recognition of a glycosylated variant of this epitope was affected to a lesser degree. A similar dominance of T cell responses to CII-glycopeptides was recorded in a cohort of severely affected RA-patients (n = 14). Thus, RA T cells predominantly recognize the immunodominant CII peptide in its glycosylated form and may explain why previously it has been difficult to detect T cell responses to CII in RA patients.}},
author = {{Bäcklund, Johan and Carlsén, Stefan and Höger, Torsten and Holm, Björn and Fugger, Lars and Kihlberg, Jan and Burkhardt, Harald and Holmdahl, Rikard}},
issn = {{1091-6490}},
language = {{eng}},
number = {{15}},
pages = {{9960--9965}},
publisher = {{National Academy of Sciences}},
series = {{Proceedings of the National Academy of Sciences}},
title = {{Predominant selection of T cells specific for the glycosylated collagen type II epitope (263-270) in humanized transgenic mice and in rheumatoid arthritis.}},
url = {{http://dx.doi.org/10.1073/pnas.132254199}},
doi = {{10.1073/pnas.132254199}},
volume = {{99}},
year = {{2002}},
}