It causes toxic shock syndrome (TSS) by stimulating the release of large amounts of interleukin-1, interleukin-2 and tumor necrosis factor.

[5] TSST-1 is a protein encoded by the tst gene, which is part of the mobile genetic element staphylococcal pathogenicity island 1.

[1] Oxygen is required in order to produce TSST-1,[7] in addition to the presence of animal protein, low levels of glucose, and temperatures between 37–40 °C (99–104 °F).

[1] Production is optimal at pH's close to neutral and when magnesium levels are low,[8] and is further amplified by high concentrations of S. aureus, which indicates its importance in establishing infection.

[12] TSST-O does not cause TSS, and is non-mitogenic, and differs in sequence from TSST-1 in 14 nucleotides, which corresponds to 9 amino acids.

[12][13] The loss of activity from these mutations is not due to changes in the protein's conformation, but instead these residues appear to be critical in the interactions with T-cell receptors.

[1] 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.

In this study a synthetic peptide containing this sequence was able to prevent SAG-induced lethality in D-galactosamine-sensitized mice with staphylococcal TSST-1, as well as some other SAGs.

Mutagenesis studies with SEA have indicated that both binding sites are required for optimal T-cell activation.

These studies containing TSST-1 indicate that the TCR binding domain lies at the top of the back side of this toxin, though the complete interaction remains to be determined.

Residues in the beta claw motif of TSST-1 are known to interact primarily with the invariant region of the Alpha chain of this MHC class II molecule.

[1] Residues forming minor contacts with TSST-1 were also identified in the HLA-DR1 β-chain, as well as the antigenic peptide, located in the interchain groove.

[1] Initial studies of mutants revealed that residues on the back side of the central alpha helix were required for super antigenic activity.

Residues Gly16, Glu132, and Gln 136, located on the back of the back-side groove of the putative TCR binding region of TSST-1, it has been proposed that they are also a part of a second functionally lethal site in the TSST-1.