Cutting edge: A test of the dominant negative signal model for TCR antagonism

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