Predominant selection of T cells specific for the glycosylated collagen type II epitope (263-270) in humanized transgenic mice and in rheumatoid arthritis.
Research output: Contribution to journal › Article
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.
|Research areas and keywords||
Subject classification (UKÄ) – MANDATORY
|Journal||Proceedings of the National Academy of Sciences|
|Publication status||Published - 2002|
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)