Selective stimulation of human T cells with streptococcal erythrogenic toxins A and B.
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.
Abe
J
J
Department of Pediatrics, National Jewish Center for Immunology and Respiratory Medicines, Denver, CO 80206.
Forrester
J
J
Nakahara
T
T
Lafferty
J A
JA
Kotzin
B L
BL
Leung
D Y
DY
D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D001426:Bacterial Proteins; D015704:CD4 Antigens / Q000032:analysis; D016827:CD8 Antigens; D004768:Enterotoxins / Q000494:pharmacology; D005098:Exotoxins / Q000494:pharmacology*; D006684:HLA-DR Antigens / Q000032:analysis; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects*; D008565:Membrane Proteins; D051379:Mice; D011749:Pyrogens / Q000494:pharmacology*; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D013297:Streptococcus pyogenes; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology
D000945:Antigens, Differentiation, T-Lymphocyte; D001426:Bacterial Proteins; D015704:CD4 Antigens; D016827:CD8 Antigens; D004768:Enterotoxins; D005098:Exotoxins; D006684:HLA-DR Antigens; D008565:Membrane Proteins; D011749:Pyrogens; D011948:Receptors, Antigen, T-Cell; C117980:SpeA protein, Streptococcus pyogenes; C027951:erythrogenic toxin; C031818:enterotoxin B, staphylococcal