Partial T cell activation with an altered superantigenic ligand.
T cells have the capacity to respond to ligands as full, weak, partial or null agonists, or indeed as antagonists. In the present paper, it is reported that staphylococcal enterotoxin B (SEB) mutated in a T cell receptor (TCR) contact site (SEBDelta61Y) behaves as an altered ligand for a T cell clone (AC20) that expresses the Vbeta17 TCR. The T cells were partially activated by SEBDelta61Y, as shown by TCR down-modulation and up-regulation of the IL-2 receptor. However, these cells did not secrete IL-2, IL-3, IL-4 or IFN-gamma, nor did they proliferate. Analysis of intracellular protein tyrosine phosphorylation after cellular activation provided further evidence that SEBDelta61Y could transduce a signal via the Vbeta17 TCR. The events following receptor ligation were clearly different when the T cells were stimulated with SEB or SEBDelta61Y, manifested as both quantitatively and qualitatively different patterns of phosphorylation of intracellular substrates. In contrast, only quantitative differences were apparent when a transfectant expressing the same alpha/beta TCR was stimulated with the different superantigens. Together, these results provide the first demonstration that altered TCR ligands are not restricted to peptides substituted at secondary TCR contact residues. Rather, an altered superantigenic ligand mutated in the TCR binding site can behave as a partial agonist.
Hayball
J D
JD
University Department of Medicine, Queen Elizabeth II Medical School, Nedlands, Western Australia, Australia. John.Hayball@imvs.sa.gov.au
Lake
R A
RA
D001665:Binding Sites / Q000235:genetics; D002999:Clone Cells; D004768:Enterotoxins / Q000235:genetics / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D006801:Humans; D008024:Ligands; D008213:Lymphocyte Activation; D016297:Mutagenesis, Site-Directed; D010766:Phosphorylation; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D018089:Superantigens / Q000235:genetics / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D014162:Transfection; D014443:Tyrosine / Q000378:metabolism
D004768:Enterotoxins; D000949:Histocompatibility Antigens Class II; D008024:Ligands; D016693:Receptors, Antigen, T-Cell, alpha-beta; D018089:Superantigens; C031818:enterotoxin B, staphylococcal; D014443:Tyrosine