Microbial superantigens stimulate T cells by the superantigen bridge and independently by a cytokine pathway.
Superantigens cross-link the MHC II molecule on accessory cells with the Vbeta region of the T cell receptor (TCR). In this study, we compared the capacity of established superantigens for inducing cytokine release. The experimental protocol was generated to answer the question whether all superantigen effects are transmitted by the MHC/TCR cross-linkage and induce mainly a T cell response. We found that TSST-1, ExFTA, and SEC3 differed from all other superantigens tested because they stimulated a stronger monokine release. T cell proliferation after challenge with these superantigens was mainly mediated by a cytokine pathway and not by the cross-linkage of MHC and TCR. For the other superantigens, we were able to demonstrate that major immunomodulatory effect is mediated by the superantigen bridge. With the exception of these three superantigens, the proliferative response of superantigens correlated with their Vbeta specificity. Interleukin-1 (IL-1) and IL-6 were induced in monocytes by all superantigens, whereas tumor necrosis factor-alpha (TNF-alpha) was induced in T cells and by some superantigens, also in monocytes. IL-2 was always induced by the superantigen bridge, whereas interferon-gamma (IFN-gamma) was also induced indirectly by monokines. Collectively, our results indicate that not all superantigens are suitable for investigating superantigen-specific effects, as they show indirect (mitogenic) side effects. Observations for an individual superantigen are, therefore, not transferable to all other superantigens.
Rink
L
L
Institute of Immunology and Transfusion Medicine, University of Lübeck School of Medicine, Germany.
Nicklas
W
W
Alvarez-Ossorio
L
L
Fagin
U
U
Kirchner
H
H
D000942:Antigens, Bacterial / Q000276:immunology*; D002455:Cell Division / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis / Q000502:physiology*; D004306:Dose-Response Relationship, Immunologic; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D007962:Leukocytes / Q000276:immunology*; D018089:Superantigens / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D000942:Antigens, Bacterial; D016207:Cytokines; D000949:Histocompatibility Antigens Class II; D007375:Interleukin-1; D015850:Interleukin-6; D018089:Superantigens; D014409:Tumor Necrosis Factor-alpha