title: An evolutionary conserved mechanism of T cell activation by microbial toxins. Evidence for different affinities of T cell receptor-toxin interaction.
abstract: The enterotoxins produced by Staphylococcus aureus are the most potent mitogens known. They belong to a group of distantly related mitogenic toxins that differ in other biologic activities. In this study we have compared the molecular mechanisms by which these mitogens activate human T lymphocytes. We used the staphylococcal enterotoxins A to E, the staphylococcal toxic shock syndrome toxin, the streptococcal erythrogenic toxins A and C (scarlet fever toxins, erythrogenic toxins (ET)A, ETC), and the soluble mitogen produced by Mycoplasma arthritidis. We found that all these toxins can activate both CD4+ and CD8+ T cells and require MHC class II expression on accessory and target cells. However, T cells could be activated in the absence of class II molecules if the toxins ETA or SEB were co-cross-linked on beads together with anti-CD8 or anti-CD2 antibodies. Enterotoxins, toxic shock syndrome toxin and scarlet toxins stimulate a major fraction of human T cells, and show preferential, but not exclusive, stimulation of T cells carrying certain TCR V beta. In contrast, the mitogen of M. arthritidis, a pathogen for rodents stimulates only a minority of human T cells but activates a major fraction of murine T cells. Analysis of human T cell clones expressing V beta 5 or V beta 8 TCR showed that these clones responded also to those toxins that did not stimulate V beta 5+ and V beta 8+ T cells in bulk cultures. These results indicate that different TCR bind to these toxins with different affinities and that the specificity of the TCR-V beta-toxin interaction is quantitative rather than qualitative in nature. Taken together our findings suggest that these toxins use a common mechanism of T cell activation. They are functionally bivalent proteins crosslinking MHC class II molecules with variable parts of the TCR. Besides V beta, other parts of the TCR must be involved in this binding. The finding that murine T cells responded more weakly to the toxins produced by the human-pathogenic bacteria than to the Mycoplasma mitogen could indicate that the toxins have been adapted to the host's immune system in evolution.
authors.affiliation: 1. Department of Medicine, University of Mainz, FRG.
authors.forename: B
authors.initials: B
authors.lastname: Fleischer
authors.forename: R
authors.initials: R
authors.lastname: Gerardy-Schahn
authors.forename: B
authors.initials: B
authors.lastname: Metzroth
authors.forename: S
authors.initials: S
authors.lastname: Carrel
authors.forename: D
authors.initials: D
authors.lastname: Gerlach
authors.forename: W
authors.initials: W
authors.lastname: Köhler
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D016827:CD8 Antigens; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic; D004768:Enterotoxins / Q000276:immunology*; D006681:HLA-D Antigens / Q000276:immunology; D006801:Humans; D066298:In Vitro Techniques; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D009174:Mycoplasma / Q000276:immunology; D011749:Pyrogens; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D013210:Staphylococcus / Q000276:immunology; D013291:Streptococcus / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D000945:Antigens, Differentiation, T-Lymphocyte; D016827:CD8 Antigens; D004768:Enterotoxins; D006681:HLA-D Antigens; D011749:Pyrogens; D011948:Receptors, Antigen, T-Cell