Previous studies by this group has shown that a component of the capsular polysaccharide of Bacteroides fragilis, known as PS A, is a potent T cell mitogen and it is involved in the production of abscess. The proposed studies will examine the structural features of PS A that affect its ability to stimulate T cell proliferation. They will examine the structural attributes of PS A that controls T cell activation and the ability of PS A to bind to cell surfaces. The second part of the study will characterize the cells responding to PS A by phenotype, by response to repeated stimulation, within the T cell repertoire, and the cytokine profile. The third part of the study will define the antigen-presenting cells and binding proteins. This work will involve characterizing the """"""""feeder cell"""""""" requirements, definition of the cell type which is important for stimulating response, and assessment of polysaccharide binding to cells. Additional studies will characterize the cell molecules important T cell stimulation and will use blocking antibody and """"""""knock-out"""""""" mice. One of the ultimate goals of this investigation is to understand how polysaccharides activate T cells, which might in turn lead to the design of the interventional strategies for potential new vaccines.
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