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.
X-ray crystallography and NMR spectroscopy were combined to reveal how neutralizing antibodies work. Top: X-ray crystallography shows where different antibodies bind SEB. Bottom: NMR spectra of SEB before (black) and after (blue) binding to a neutralizing antibody reveal chemical shift perturbations to the toxin’s TCR and MHC binding sites.
Research article: Dutta et al. 2015; J Biol Chem. 290(11):6715-30