A T-CELL RECEPTOR (TCR) ANTAGONIST COMPETITIVELY INHIBITS SERIAL TCR TRIGGERING BY LOW-AFFINITY LIGANDS, BUT DOES NOT AFFECT TRIGGERING BY HIGH-AFFINITY ANTI-CD3 ANTIBODIES

It has been demonstrated that modified peptides which fail to induce d etectable T cell responses can act as T cell receptor (TCR) antagonist s when presented together with agonist by the same antigen-presenting cell (APC). We report that a TCR antagonist competitively inhibits TCR triggering induced by low-affinity ligands such as agonistic peptides or bacterial superantigens. However, the same antagonist cannot inhib it TCR triggering and T cell activation induced by high-affinity anti- CD3 antibodies that engage most TCR at once. These results indicate th at TCR antagonists inhibit T cell responses by interfering with the on going process of serial triggering, rather than by delivering an inhib itory signal to T cells.