Neutralization Mechanisms of Staphylococcal Enterotoxin B by Monoclonal Antibodies
Staphylococcal enterotoxin B (SEB) is a superantigen that can simultaneously bind to MHC proteins on the surface of most cells and TCR receptors expressed by immune T cells. This interaction activates a large number of T cells, causing high fevers and potentially death. Neutralizing antibodies are currently the only therapeutic option and must be optimized to work post-exposure. Using both X-ray crystallography and NMR spectroscopy, NYSBC scientists have mapped the binding sites of several neutralizing antibodies on SEB and discovered conformational changes induced by these bindings.
These findings have elucidated the different mechanisms by which single and combinations of antibodies neutralize SEB toxicity, namely direct competition for the TCR receptor binding site on SEB and allosteric induction of conformational changes that reduce SEB interactions with both TCR and MHC. These studies can be used to optimize anti-SEB therapies. Additionally, specific regions of these antibodies were identified where re-engineering could be used to expand their protective properties to multiple related toxins.
Research article: Dutta et al. 2015; J Biol Chem. 290(11):6715-30