The overall goal of my research, which I perform in collaboration with Drs. Michael W. Russell and Terry D. Connell, is to elucidate the mechanisms by which LT-IIa, LT-IIb and CT exert their potent mucosal and systemic antibody adjuvant activities.

LT-IIa, LT-IIb and CT are bacterial enterotoxins that bind to different ganglioside receptors that are expressed on B cells, T cells and dendritic cells (DC). It is proposed that the humoral adjuvant activities of the three enterotoxins are governed, at least in part, by their receptor-binding specificities, and by their inherent capacity to modulate membrane lipid raft distribution and composition in B cells, T cells and DC.

We are currently studying the effects of the three enterotoxins on Ag uptake, MHC-II and costimulatory molecule expression by B cells and DC, and the effect of LT-IIa, LT-IIb and CT on the induction of B cell responses by T cells and DC.

As differentiation of B cells into antibody secreting cells often requires direct physical contact between B cells, T cells and DC, and soluble cytokines derived from T cells and DC, we are also studying the effects of LT-IIa, LT-IIb and CT on the expression of contact-dependent signals and cytokines by T cells and DC.

Finally, we also investigate the ganglioside and specific costimulatory molecule composition of lipid rafts isolated from B cells, T cells, and DC in order to elucidate whether various costimulatory and adhesion molecules which are involved in T-cell-B-cell-DC interactions are constitutively associated or become associated or become associated with lipid rafts in those cell types during enterotoxin treatment.

It is hoped that our research will be useful toward developing new and more potent mucosal vaccines against pathogenic microorganisms and tumors.