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Predominant selection of T cells specific for the glycosylated collagen type II epitope (263-270) in humanized transgenic mice and in rheumatoid arthritis.
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- Bäcklund, Johan (author)
- Lund University,Lunds universitet,Immunologi,Forskargrupper vid Lunds universitet,Immunology,Lund University Research Groups
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- Carlsén, Stefan (author)
- Lund University,Lunds universitet,Immunologi,Forskargrupper vid Lunds universitet,Immunology,Lund University Research Groups
- Höger, Torsten (author)
- show more...
- Holm, Björn (author)
- Fugger, Lars (author)
- Kihlberg, Jan (author)
- Burkhardt, Harald (author)
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- (creator_code:org_t)
- 2002-06-27
- 2002
- English.
- In: Proceedings of the National Academy of Sciences. - : Proceedings of the National Academy of Sciences. - 1091-6490 .- 0027-8424. ; 99:15, s. 9960-9965
- Journal article (peer-reviewed)
Abstract
Subject headings
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- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Immunology in the medical area (hsv//eng)
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- art (subject category)
- ref (subject category)
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- Holmdahl, Rikard
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