Staphylococcal enterotoxins (SEs) are emetic toxins that cause the intoxication staphylococcal food poisoning syndrome. In addition to causing emesis, the SEs have a number of other biological activities. The SEs interact with T cell receptors in the presence of class II major histocompatibility antigens resulting in T cell proliferation and release of cytokines (mimicking the Mls-1 response). At the molecular level very little is known about the SE's mechanism of action for any of these biological activities; the relationship between emesis and T cell-macrophage interaction is not clear. The significance of the SE's immunological properties is not well understood. But there is epidemiological and experimental evidence showing that the SEs are important virulence factors in some Toxic Shock Syndrome cases and many of the symptoms may be due to SE induced cytokine secretion. I am taking molecular biological and biochemical approaches to elucidate the relationship between SE's structure and function because very little is known. This proposal has two parts. (Specific Aim #1) A map of staphylococcal enterotoxin type A (SEA) will be constructed that defines peptide domains that are and are not required for SEA's various biological activity. This will be done using molecular biological techniques to construct Ma mutations and assaying the resulting altered-SEA for their -biological activities. (Specific Aim #2) The structure of SEA will be solved by x-ray diffraction analysis of crystals. Detailed structure-activity information obtained from the proposed research will be necessary for elucidation of the molecular mechanism for SEA's biological activities which include understanding immune system biology and may have applications for understanding some neurological-hormonal interactions. In addition, information from these studies could lead to development of SEA based therapeutic agents that are immunopotentiating agents.
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