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T cell responses to a non-glycosylated epitope predominate in type II collagen-immunized HLA-DRB1*0101 transgenic mice
  1. Alexei von Delwig (alexei.delwig{at}ncl.ac.uk)
  1. School of Clinical Medical Sciences, United Kingdom
    1. Daniel M Altmann
    1. Imperial College, United Kingdom
      1. Fraser G Charlton
      1. Royal Victoria Infirmary, United Kingdom
        1. Norman McKie
        1. Newcastle University, United Kingdom
          1. John D Isaacs
          1. Newcastle University, United Kingdom
            1. Rikard Holmdahl
            1. Lund University, Sweden
              1. John H Robinson
              1. Newcastle University, United Kingdom

                Abstract

                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

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