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The Journal of Immunology, 1999, 163: 1750-1754.
Copyright © 1999 by The American Association of Immunologists


CUTTING EDGE

Cutting Edge: Dueling TCRs: Peptide Antagonism of CD4+ T Cells with Dual Antigen Specificities1

Jennifer M. Robertson and Brian D. Evavold2

Department of Microbiology and Immunology, Emory University, Atlanta, GA, 30322

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 Vß-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.




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