Cutting edge: Dueling TCRs: Peptide antagonism of CD4(+) T cells with dualantigen specificities

T cells expressing two different TCRs were generated by interbreeding 3A9 a nd AND CD4(+) TCR transgenic mice specific for the hen egg lysozyme (HEL) p eptide 48-62:I-A(k) and moth cytochrome c (MCC) peptide 88-103:1-E-k peptid e:MHC ligands, respectively. Peripheral T cells in the offspring express tw o TCR VP-chains and respond to HEL and MCC. We observed minimal or no addit ive effects upon simultaneous suboptimal stimulation with both agonist pept ides; however, an antagonist peptide for the 3A9 TCR was able to inhibit th e response of the dual receptor T cells to MCC, the AND TCR agonist. This H EL antagonist peptide did not affect AND single transgenic T cells, indicat ing 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 rec eptor-specific antagonism These results demonstrate that peptide antagonism exerts a dominant effect.