Superantigens (SAgs) are a class of
antigens that cause non-specific activation of T-cells resulting in polyclonal T cell activation and massive
cytokine release and causing symptoms similar to
sepsis, e.g.
hypotension and subsequent hyporeactivity. We investigated the direct effect of SAgs on vascular tone using two recombinant SAgs, SEA and SPEA. The roles of
Nitric Oxide (NO) and potentially hyperpolarization, which is dependent on the K+ channel activation, were also explored. The data show that SEA and SPEA have direct vasodilatory effects that were in part NO-dependent, but completely dependent on activation of K+ channels. Our work also identified the functional regions of one of the
superantigens, SPEA, that are involved in causing the vasodilation and possible
hypotension. A series of 20 overlapping
peptides, spanning the entire sequence of SPEA, were designed and synthesized. The vascular response of each
peptide was measured, and the active
peptides were identified. Our results implicate the regions, (61-100), (101-140) and (181-220) which cause the vasodilation and possible
hypotension effects of SPEA. The data also shows that the
peptide 181-220 exert the highest vasodilation effect. This work therefore, demonstrates the direct effect of SAgs on vascular tone and identify the active region causing this vasodilation. We propose that these three
peptides could be effective novel
antihypertensive drugs. We also overexpressed, in E.coli, four
superantigens from
codon optimized genes.