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The mechanism by which TCR antagonists interfere with T cell activation is unclear. Inhibition of T cell activation by TCR antagonists is a well-established phenomenon 1 , 2 , 3 , yet the mechanism by which this inhibition occurs remains obscure. This data was interpreted to mean that such inhibition was not due to simple receptor competition, but rather that antagonists generate a negative signal that would block the activation cascade induced by agonists. Indirect support for this idea came from data demonstrating that TCR antagonists could partially inhibit responses to bystander APC presenting agonist ligands 12 , 15 , While consistent with a dominant negative model for antagonism, these data do not exclude mechanisms based on receptor competition, especially in light of T cell activation models involving serial triggering 17 , 18 and data demonstrating antagonists with higher TCR affinity than weak agonists

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