title: Cutting edge: dueling TCRs: peptide antagonism of CD4+ T cells with dual antigen specificities.
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.
authors.affiliation: Department of Microbiology and Immunology, Emory University, Atlanta, GA 30322, USA.
authors.forename: J M
authors.initials: JM
authors.lastname: Robertson
authors.forename: B D
authors.initials: BD
authors.lastname: Evavold
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000918:Antibody Specificity; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002460:Cell Line; D002645:Chickens; D003574:Cytochrome c Group / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D007166:Immunosuppressive Agents / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008805:Mice, Inbred A; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009036:Moths; D009113:Muramidase / Q000037:antagonists & inhibitors / Q000276:immunology; D010446:Peptide Fragments / Q000819:agonists / Q000037:antagonists & inhibitors / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D003574:Cytochrome c Group; D018984:Epitopes, T-Lymphocyte; D007166:Immunosuppressive Agents; D010446:Peptide Fragments; D011948:Receptors, Antigen, T-Cell; D009113:Muramidase