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T cell responses to a non-glycosylated epitope predominate in type II collagen-immunised HLA-DRB1*0101 transgenic mice


Aim: To study collagen-induced arthritis in human leucocyte antigen (HLA)-DR1 transgenic mice lacking endogenous major histocompatibility complex class II molecules (MHC-II) and to determine 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 immunisation 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. Most of the T cell hybridomas generated from CII-immunised mice recognised 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: This 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.

  • APC, antigen presenting cells
  • CFA, complete Freund’s adjuvant
  • CIA, collagen-induced arthritis
  • DC, dendritic cells
  • FITC, fluorescein isothiocyanate
  • HLA, human leucocyte antigen
  • IFA, incomplete Freund’s adjuvant
  • MHC-II, major histocompatibility complex class-II
  • PBS, phosphate-buffered saline
  • PE, phycoerythrin
  • RA, rheumatoid arthritis
  • TCR, T cell receptor
  • TG, transgenic

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