Cross-antagonism of a T cell clone expressing two distinct T cell receptors

Inhibition of T cell activation can be mediated by analogs of the original antigenic peptide (TCR antagonists). Here, a T cell clone expressing two di stinct TCR was used to investigate whether such inhibition involves an acti ve mechanism by examining whether an antagonist for one TCR could influence responses stimulated by the other TCR engaging its agonist. Our results de monstrate functional cross-inhibition under these conditions involving the ability of antagonist: TCR interactions to diminish Lck enzymatic activity associated with the agonist-recognizing second TCR, apparently through enha ncement of SHP-1 association with these receptors. Our findings reveal that inhibition of cellular responses by antagonists arises at least in part fr om active negative regulation of proximal TCR signaling and identify elemen ts of the biochemical process.