The ability to maintain a state of controlled inflammation is a feature unique to the gut associated lymphoid tissue. We have identified a novel cell in the regulation of this state. the normal intestinal enterocyte. This cell is fully capable of engulfing antigen, processing it and presenting the resultant immunogenic peptides to antigen primed T cells. However, in contrast to conventional antigen presenting cells, epithelial cells of the gut appear to selectively stimulate antigen non-specific suppressor T cells. We have identified the essential parameters of antigen presenting cell function in these cells over the past two years, including the finding that these cells stimulate suppressor T cells. In the next period, we propose to carefully dissect out mechanisms of CD8+ T cell stimulation. Our current data suggest that a novel CD8 ligand might exist on normal enterocytes but that aberrant processing, of antigen may also play a role in specific T cell activation. We purpose studies to identify a novel CD8 ligand by monoclonal antibody technology, isolation of potential ligands, and determination of CD8 binding and potential signal transduction pathways using the src-like tyrosine protein kinase, p56lck. In addition, we will seek to determine whether antigen uptake and processing is a physiologic event in the normal GI tract, by assessing, uptake and processing events by following, labelled proteins into the cell and through the degradative endolysosomal pathways, using fluoresceinated and radiolabelled proteins. In this manner, we will develop a better understanding of the normal mechanisms for antigen handling, in the intestine and add insights into disease processes, where antigen handling, may be aberrant.
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