The long-term objective of this proposal is to investigate some of the factors that moderate superantigen recognition in order to more clearly define the in vivo effects of superantigens. While the toxic effect of some bacterial superantigens is known, other deleterious health risks from both bacterial and viral superantigens are still under investigation, and may include induction of autoimmune disease and the immune dysfunction associated with HIV infection. The major goal of this proposal is to define how MHC-assoCiated peptides and TCR/MHC interactionS modulate superantigens activity, since the strength of superantigen recognition differentially affects the fate of T cells. The experiments proposed in this application will determine: (1) the mechanisms of which MHC-bound peptides regulate bacterial superantigen presentation to T-cells, and (2) whether recognition of SEA or TSST-1 is influenced by MHC polymorphism. These experiments are designed to address superantigen activity at the molecular level, and will lead to a better understanding of human diseases they cause and for their potential use in immune therapy.
