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Ann Rheum Dis 66:599-604 doi:10.1136/ard.2006.061945
  • Extended report

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

  1. Alexei von Delwig1,
  2. Daniel M Altmann2,
  3. Fraser G Charlton3,
  4. Norman McKie1,
  5. John D Isaacs1,
  6. Rikard Holmdahl4,
  7. John H Robinson1
  1. 1Institute of Cellular Medicine, Newcastle University, Framlington Place, Newcastle upon Tyne, UK
  2. 2Human Immunogenetics, Hammersmith Hospital, London, UK
  3. 3Royal Victoria Infirmary, Newcastle upon Tyne, UK
  4. 4Department of Cell and Molecular Biology, Lund University, Sweden
  1. Correspondence to:
    Dr Alexei von Delwig
    Institute of Cellular Medicine, Newcastle University, Framlington Place, Newcastle upon Tyne, NE2 4HH, UK; alexei.delwig{at}ncl.ac.uk
  • Accepted 2 November 2006
  • Published Online First 17 November 2006

Abstract

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.

Footnotes

  • Published Online First 17 November 2006

  • Competing interests: None declared.