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

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Abstract
It has been demonstrated that modified peptides which fail to induce detectable T cell responses can act as T cell receptor (TCR) antagonists 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 inhibit TCR triggering and T cell activation induced by high‐affinity anti‐CD3 antibodies that engage most TCR at once. These results indicate that TCR antagonists inhibit T cell responses by interfering with the ongoing process of serial triggering, rather than by delivering an inhibitory signal to T cells.