Toxic Shock Syndrome Toxin - Mechanism

Mechanism

A superantigen such as TSST-1 stimulates human T cells that express VB 2, which may represent 5-30% of all host T cells. PTSAgs induce the VB-specific expansion of both CD4 and CD8- subsets of T Lymphocytes. TSST-1 forms homodimers in most of its known crystal forms. The SAGs show remarkably conserved architecture and are divided into the N- and C- terminal domains. Mutational analysis has mapped the putative TCR binding region of TSST-1 to a site located on the back-side groove. If the TCR occupies this site, the amino terminal alpha helix forms a large wedge between the TCR and MHC class II molecules. The wedge would physically separate the TCR from the MHC class II molecules. A novel domain may exist in the SAGs that is separate from the TCR and class II MHC-binding domains. The domain consists of residues 150 to 161 in SEB, and similar regions exist in all the other SAGs as well. In this study a synthetic peptide containing this sequence was able to prevent SAG-induced lethality in D-galactosamine-sensitized mice with staphylcoccal TSST-1, as well as some other SAGs. Significant differences exist in the sequences of MHC Class II alleles and TCR Vbeta elements expressed by different species, and these differences have important effects on the interaction of PTSAgs and with MCH class II and TCR molecules.