TCR antagonist peptides induce formation of APC-T cell conjugates and activate a Rac signaling pathway

T cell receptor antagonists inhibit T cell activation by antigen, and by th emselves fail to induce phenotypic changes associated with T cell activatio n. However, they can induce limited tyrosine phosphorylation of TCR zeta ch ain. Here we show that TCR antagonists are potent inducers of APC-T cell co njugates, cytoskeletal reorganization, and capping of certain T cell protei ns. These events are associated with a signaling pathway involving tyrosine phosphorylation of Vav and SLP-76, activation and capping of Rac-1, a prot ein previously linked with cytoskeletal reorganization, and activation of J NK. The finding that antagonist peptides stimulate this pathway, while fail ing to stimulate other TCR-mediated signaling pathways, indicates the prese nce in T cells of a hierarchy of signaling that is sensitive to the avidity of Ag/MHC-TCR interaction.