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Specificity of an HLA-DRB1*0401-restricted T cell response to type II collagen
L Fugger1, J B Rothbard, G Sonderstrup-McDevitt
1Department of Microbiology and Immunology, Stanford University School of Medicine, USA. fugger@inet.uni-c.dk
A panel of HLA-DRB1*0401-restricted CD4+ mouse T cell hybridomas specific for bovine type II collagen were generated from transgenic mice expressing the human HLA-DRA1*0101/-DRB1*0401 and CD4 molecules. The vast majority recognized a single peptide determinant corresponding to residues 261-273 (CII 261-273). This determinant was rapidly defined by the use of a predictive algorithm for peptide binding to DRB1*0401. CII 261-273 is conserved in bovine and human type II collagen and overlaps with an important I-A q - restricted T cell determinant in mice with collagen-induced arthritis. This study demonstrates how HLA-DR and human CD4-transgenic mice can be used to identify a T cell epitope in a potential or candidate autoantigen.
A panel of HLA-DRB1*0401-restricted CD4+ mouse T cell hybridomas specific for bovine type II collagen were generated from transgenic mice expressing the human HLA-DRA1*0101/-DRB1*0401 and CD4 molecules. The vast majority recognized a single peptide determinant corresponding to residues 261-273 (CII 261-273). This determinant was rapidly defined by the use of a predictive algorithm for peptide binding to DRB1*0401. CII 261-273 is conserved in bovine and human type II collagen and overlaps with an important I-A q - restricted T cell determinant in mice with collagen-induced arthritis. This study demonstrates how HLA-DR and human CD4-transgenic mice can be used to identify a T cell epitope in a potential or candidate autoantigen.