Altered superantigenic ligands demonstrate the quantitative nature of T-cell activation

In a recent study, a superantigen mutated in the TCR binding site (staphylo coccal enterotoxin B (SEB)Delta 61Y) was described, which behaved as a part ial agonist for a V beta 17-expressing T-cell clone. Evidence is now presen ted to demonstrate that there is distinct heterogeneity in the response of primary T cells to this protein. Some V beta 17 T cells responded to SEB De lta 61Y by modulating surface receptor expression consistent with activatio n, and by proliferating. Other V beta 17 T cells did not proliferate, nor d id they display a receptor expression phenotype consistent with activation. However, when repeatedly exposed to the altered superantigen, some of thes e non-responders entered cell cycle. This pattern of responses was not reca pitulated by providing additional costimulation via CD28, although such tre atment did induce some of the 'unresponsive' V beta 17 T cells to upregulat e the IL-2 receptor, indicative of partial activation. It was also found th at the heterogeneous pattern could be replicated using very low doses of na tive SEB. The data are discussed in the context of models of T-cell activat ion in which differences in TCR ligand affinity and dose determine qualitat ively different response phenotypes.