Investigating mechanisms of neutralization of staph enterotoxin B

Abstract

Staphylococcal enterotoxin B (SEB) is a small, secreted protein that causes food poisoning-like symptoms and can be lethal in microgram amounts. SEB elicits a profound immune response via the bridging of major histocompatibility complex class II (MHCII) molecules on antigen-presenting cells with T-cell receptors (TCR). Several monoclonal antibodies (mAbs) have been identified as capable of neutralizing SEB. Using structural mass spectrometry, the epitopes of several neutralizing antibodies were successfully mapped, and allosteric as well as synergistic effects that contribute to the efficacy of select mAbs were determined. Having established a robust approach for tracking mAb-SEB interactions, we examined the interactions within raw, polyclonal sera for understanding antibody responses to SEB and their resulting protective efficacy. This dissertation provides mechanistic insight into the neutralization of SEB and highlights technical advances to the Hydrogen Deuterium Exchange Mass Spectrometry (HDX-MS) method.