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 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.
Viola
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Basel Institute for Immunology, Switzerland. viola@bii.ch
Linkert
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Lanzavecchia
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D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D001427:Bacterial Toxins; D001667:Binding, Competitive / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology*; D002999:Clone Cells; D015536:Down-Regulation / Q000276:immunology; D004768:Enterotoxins / Q000494:pharmacology; D006801:Humans; D008024:Ligands; D008213:Lymphocyte Activation / Q000187:drug effects; D010446:Peptide Fragments / Q000276:immunology / Q000494:pharmacology*; D011948:Receptors, Antigen, T-Cell / Q000819:agonists / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000378:metabolism*; D018089:Superantigens; D013601:T-Lymphocytes / Q000276:immunology
D000911:Antibodies, Monoclonal; D001427:Bacterial Toxins; D017252:CD3 Complex; D004768:Enterotoxins; D008024:Ligands; D010446:Peptide Fragments; D011948:Receptors, Antigen, T-Cell; D018089:Superantigens; C030107:enterotoxin F, Staphylococcal