Selective stimulation of human T cells with streptococcal erythrogenic toxins A and B.

Abstract

Streptococcal exotoxins have been implicated in the pathogenesis of a toxic shock-like syndrome and scarlet fever. Previous studies have demonstrated that these toxins are potent stimulators of human T cells and have structural homology to staphylococcal enterotoxins. In the current study, we investigated the mechanism by which streptococcal erythrogenic toxins type A (SPEA) and B (SPEB) activate T cells and compared it with anti-CD3 and the known "superantigen" staphylococcal enterotoxin B. SPEA was found to selectively activate T cells bearing V beta 8, V beta 12, and V beta 14, whereas SPEB selectively activated T cells bearing V beta 2 and V beta 8. Furthermore, fibroblasts transfected with MHC class II molecules were capable of presenting SPEA and SPEB to purified T cells. The T cell response to these toxins, however, was not MHC-restricted. Although the streptococcal exotoxins stimulated both CD4+ and CD8+ T cells, SPEA but not SPEB stimulated the CD4+ T cell subset proportionately more than the CD8+ T cell subset. Our results indicate that SPEA and SPEB, like the staphylococcal enterotoxins, are superantigens and suggest a mechanism by which they may mediate particular systemic syndromes associated with streptococcal infections.

The superantigens SpeC and TSST-1 specifically activate TRBV12-3/12-4+ memory T cells

“…An earlier study reported that TRBV12-3/12-4 + cells became activated in response to stimulation with SpeC 62 . However, this result was later questioned by the same group of investigators 63 , who suspected contamination of the original SAg preparation with SpeA, which is known to exhibit specificity for TRBV12-3/12-4 + TCRs 64 , 65 . In particular, they found that recombinant SpeC did not induce the secretion of IL-2 from Jurkat cells expressing TRBV12-3/12-4 + TCRs 63 , even in the presence of Raji cells to compensate for a lack of HLA-DQ and HLA-DR 66 .…”