Abstract
T cells expressing two different TCRs were generated by interbreeding 3A9 and AND CD4+ TCR transgenic mice specific for the hen egg lysozyme (HEL) peptide 48-62:I-Ak and moth cytochrome c (MCC) peptide 88-103:I-Ek peptide:MHC ligands, respectively. Peripheral T cells in the offspring express two TCR V beta-chains and respond to HEL and MCC. We observed minimal or no additive effects upon simultaneous suboptimal stimulation with both agonist peptides; however, an antagonist peptide for the 3A9 TCR was able to inhibit the response of the dual receptor T cells to MCC, the AND TCR agonist. This HEL antagonist peptide did not affect AND single transgenic T cells, indicating that the antagonism observed in the dual TCR cells is dependent on the presence of the HEL-specific 3A9 TCR. In contrast, anti-TCR Abs mediate receptor-specific antagonism. These results demonstrate that peptide antagonism exerts a dominant effect.
Publication types
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Research Support, Non-U.S. Gov't
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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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Antibodies, Monoclonal / pharmacology
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Antibody Specificity
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CD4-Positive T-Lymphocytes / immunology*
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CD4-Positive T-Lymphocytes / metabolism
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Cell Line
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Chickens
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Cytochrome c Group / immunology
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Epitopes, T-Lymphocyte / biosynthesis*
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Epitopes, T-Lymphocyte / genetics
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Epitopes, T-Lymphocyte / immunology
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Immunosuppressive Agents / immunology
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Lymphocyte Activation
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Mice
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Mice, Inbred A
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Mice, Inbred C57BL
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Mice, Transgenic
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Molecular Sequence Data
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Moths
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Muramidase / antagonists & inhibitors
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Muramidase / immunology
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Peptide Fragments / agonists
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Peptide Fragments / antagonists & inhibitors
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Peptide Fragments / immunology*
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Receptors, Antigen, T-Cell / antagonists & inhibitors*
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Receptors, Antigen, T-Cell / genetics
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Receptors, Antigen, T-Cell / immunology
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T-Lymphocyte Subsets / immunology*
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T-Lymphocyte Subsets / metabolism
Substances
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Antibodies, Monoclonal
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Cytochrome c Group
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Epitopes, T-Lymphocyte
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Immunosuppressive Agents
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Peptide Fragments
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Receptors, Antigen, T-Cell
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Muramidase