Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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Animals
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Arthritis / immunology
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Arthritis, Rheumatoid / immunology
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Cattle
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Collagen / chemistry
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Collagen / classification
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Collagen / immunology*
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Collagen / toxicity
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Cytotoxicity, Immunologic
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Disease Models, Animal
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Epitopes / chemistry
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Epitopes / immunology*
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HLA-DR Antigens / immunology*
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HLA-DRB1 Chains
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Histocompatibility Antigens Class II / immunology
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Humans
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Hybridomas / immunology
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Isoantigens / chemistry
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Isoantigens / immunology
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Mice
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Mice, Inbred A
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Mice, Inbred DBA
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Mice, Transgenic
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Molecular Sequence Data
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Peptide Fragments / chemical synthesis
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Peptide Fragments / immunology
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T-Lymphocyte Subsets / immunology*
Substances
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Epitopes
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HLA-DR Antigens
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HLA-DRB1 Chains
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HLA-DRB1*04:01 antigen
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Histocompatibility Antigens Class II
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Isoantigens
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Peptide Fragments
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Collagen