Objective: We studied collagen-induced arthritis in HLA-DR1 transgenic mice lacking endogenous MHC class II molecules (MHC-II) and determined T cell specificity against the arthritogenic CII259-273 epitope of type II collagen either unmodified or post-translationally glycosylated at Lys264.
Methods: Arthritis was induced by immunization with human type II collagen in Complete Freund's adjuvant and measured by footpad swelling, clinical score and histology. T cell responses were assessed by proliferation of spleen and lymph node cells and in antigen presentation assays using T cell hybridomas specific for the glycosylated and non-glycosylated CII259-273 epitope.
Results: The incidence of arthritis was 50% in DR1-transgenic mice lacking endogenous MHC-II molecules. Recall T cell responses in draining lymph nodes and spleen were consistently greater against the non- glycosylated epitope than to the glycosylated CII259- 273. The majority of T cell hybridomas generated from CII-immunized mice recognized the non-glycosylated CII epitope and this form of the epitope was also presented with 100-fold higher efficiency and 1 h faster kinetics by both macrophages and dendritic cells.
Conclusion: Our study shows that T cell responses to the non-glycosylated epitope of heterologous (human) CII are dominant in HLA-DR1 transgenic mice lacking MHC- II, which could contribute to the pathogenicity of autoimmune arthritis.
- antigen presentation
- arthritogenic T cell epitope
- collagen-induced arthritis
- post-translational modification
- type II collagen