Antagonism of superantigen-stimulated helper T-cell clones and hybridomas by altered peptide ligand.
T-cell activation by an immunogenic peptide can be antagonized by nonstimulatory analogs of that peptide. We investigated this T-cell receptor antagonism by using staphylococcal enterotoxin superantigen to stimulate hemoglobin-specific helper T (Th) cells because its activation pathway may differ from that of conventional antigen. Interestingly, superantigen activation of these Th cells was antagonized by hemoglobin peptide analogs even though agonist (superantigen) and antagonist (analog peptide) bind at different sites on the major histocompatibility complex-encoded molecule and the T-cell receptor. The antagonism appeared to be a fundamental block in T-cell activation, as phosphoinositol generation, cytokine production, and proliferation were reduced in Th1 clones, and, similarly, proliferative and cytokine responses were inhibited in Th2 cells. Even T-cell hybridoma activation (cytokine production and apoptosis) was inhibited by peptide antagonists. Furthermore, analog peptides that functioned as partial agonists for these Th cells also antagonized superantigen-induced proliferation and thus were a subset of the peptide antagonists. In summary, our results demonstrate that analogs of immunogenic peptide are potent antagonists for Th cell responses induced by superantigen as well as immunogenic peptide.
Evavold
B D
BD
Department of Pathology, Washington University School of Medicine, St. Louis, MO 63110.
Sloan-Lancaster
J
J
Allen
P M
PM
D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D002999:Clone Cells; D005260:Female; D006454:Hemoglobins / Q000737:chemistry / Q000378:metabolism; D006825:Hybridomas; D008213:Lymphocyte Activation; D051379:Mice; D008808:Mice, Inbred CBA; D008969:Molecular Sequence Data; D010716:Phosphatidylinositols / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000037:antagonists & inhibitors; D018089:Superantigens / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
D006454:Hemoglobins; D010716:Phosphatidylinositols; D011948:Receptors, Antigen, T-Cell; D018089:Superantigens