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Type B T cells specific for an arthritogenic epitope of proteoglycan aggrecan recognize ligands released from degrading cartilage
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Dr Jane Falconer
Dr Rahul Mahida
Professor John Robinson
Falconer J, Mahida R, Venkatesh D, Pearson J, Robinson JH
Journal of Immunology
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It has been proposed that peptide epitopes bind to MHC class II molecules to form distinct structural conformers of the same MHC-II-peptide complex termed type A and type B, and that the two conformers of the same peptide-MHC-II complex are recognized by distinct CD4 T cells, termed type A and type B T cells. As type B T cells that recognise exogenous self peptides have been shown to escape negative selection during thymic development they have the potential to contribute to the pathogenesis of autoimmunity. 0 0 1 211 1203 Newcastle University 10 2 1412 14.0 Normal 0 false false false EN-GB JA X-NONE We generated and characterised mouse CD4 T cells specific for an arthritogenic epitope of the candidate joint autoantigen proteoglycan aggrecan. Cloned T cell hybridomas specific for a synthetic peptide containing the aggrecan epitope divided into two groups based on their ability to recognise intact aggrecan and fine mapping demonstrated that both types of T cell recognised the same core epitope. The data is consistent with the generation of aggrecan-specific type A and type B T cells. Type B T cells were activated by supernatants released from degrading cartilage indicating the presence of antigenic fragments of aggrecan. We suggest that type B T cells could play a role in the pathogenesis of proteoglycan-induced arthritis in mice, a model for Rheumatoid Arthritis in man, by recognising extracellular peptides or protein fragments of joint autoantigens released by inflamed cartilage.
American Association of Immunologists
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