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The Journal of Immunology, 1999, 162: 3761-3764.
Copyright © 1999 by The American Association of Immunologists


CUTTING EDGE

Cutting Edge: A Test of the Dominant Negative Signal Model for TCR Antagonism1

Mark A. Daniels, Sonya L. Schober, Kristin A. Hogquist and Stephen C. Jameson2

Center for Immunology and Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN 55455

The mechanism by which TCR antagonists interfere with T cell activation is unclear. One popular hypothesis is that incomplete early signaling events induced by these ligands dominantly inhibit the T cell’s ability to respond to a copresented agonist ligand. Here we test this "dominant negative" signal hypothesis by studying T cells expressing two distinct MHC class I-restricted TCRs (2C and OT-I). Although responses through each TCR can be efficiently inhibited by their specific antagonists, we found no evidence for "cross-antagonism" in which an antagonist for receptor "A" blocks responses through receptor "B." Such inhibition would have been expected were the dominant negative signaling hypothesis correct, and alternative models for TCR antagonism are discussed.




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