STIMULATION OF HUMAN T-CELLS BY MICROBIAL SUPERANTIGENS

The enterotoxins and the TSST of S. aureus, the erythrogenic toxins A and C of S. pyogenes and a still uncharacterized exoprotein of M. arthritidis belong to a family of exotoxins that have in common a potent mitogenic activity for T lymphocytes of several species. These proteins stimulate CD4+ and C8+ T cells, as well as a fraction of gamma-delta-TCR-bearing T cells by cross-linking variable parts of the T cell antigen receptor with MHC class II molecules on accessory or target cells. They are functionally bivalent molecules having distinct interaction sites for variable parts of the TCR and for nonpolymorphic parts of the MHC class II molecule. For alpha-beta-TCR-bearing T cells the V-beta is the dominant site of interaction with the toxins. However, there is only a preferential but not exclusive stimulation of T cells carrying a certain V-beta, because T cell clones carrying e.g. V-beta-5 or V-beta-8 can respond also to those toxins that do not stimulate V-beta-5+ and V-beta-8+ T cells in bulk cultures. Therefore, different TCR bind to these toxins with different affinities and the specificity of the TCR-toxin interaction is quantitative rather than qualitative in nature. Murine T cells respond to the mitogen of M. arthritidis that is a natural pathogen for mice and rats much better than to the toxins of the human pathogenic bacteria, whereas the opposite is true for human T cells. This could indicate that the toxins have been adapted to the host's immune system in evolution. The T cell-stimulating activity contributes to the pathogenesis of the respective diseases.