Zinc regulates the function of two superantigens.

Area of Science:

• Immunology
• Biochemistry
• Microbiology

Background:

• Staphylococcal enterotoxins are potent bacterial superantigens that bind to MHC class II proteins.
• This binding triggers widespread T cell activation via the T-cell receptor V beta region, leading to toxic effects.

Purpose of the Study:

• To investigate the role of metal ions in the binding of staphylococcal enterotoxins to major histocompatibility complex (MHC) proteins.
• To elucidate the mechanism by which enterotoxins bind to MHC molecules and stimulate T cells.

Main Methods:

• Utilized EDTA to chelate metal ions and assess their effect on enterotoxin-MHC binding.
• Investigated the effect of various divalent metal ions (Zn2+, Ca2+, Mg2+, Cu2+, Fe2+, Mn2+) on binding.
• Determined the dissociation constant (Kd) for zinc binding to enterotoxin A and its effect on enterotoxin-MHC binding using purified proteins.

Main Results:

• EDTA abolished binding of enterotoxin A and E to HLA-DR, but not toxic shock toxin.
• Zinc ions (Zn2+) fully reconstituted binding, while other metal ions had no effect.
• Zinc binding to enterotoxin A occurred at a single site with a Kd of 2 microM, independent of HLA-DR1.
• Zinc binding is essential for forming the MHC binding domain of these superantigens, with a Kd of 25 nM for enterotoxin A binding to HLA-DR1 in the presence of zinc.

Conclusions:

• Zinc binding is a critical initial step for the interaction of staphylococcal enterotoxins A and E with MHC class II molecules.
• Physiological serum zinc concentrations may regulate the toxic effects mediated by these superantigens.