The long range goal of these studies is to provide a detailed understanding of the mechanism by which macrophages process and present antigen to lymphocytes. In this regard, attempts will be made to understand the interactions of macrophages with the facultative intracellular pathogen Listeria monocyogenes. Assays for macrophage-dependent T lymphocyte activation in vitro will be used. Antigenic determinants associated with the bacteria and expressed by macrophages infected with the bacteria will be detected with monoclonal antibodies and T cell lines and hybridomas. Detailed study of the antigenic structures of L monocytogenes will be performed using such tools in combination with molecular genetic techniques. The molecular and cellular mechanisms underlying the differential requirements for antigen processing requirements with different forms of listerial antigens will be studied. Experiments will be performed to evaluate the effects of the fungal polypeptide, cyclosporine, on macrophage-dependent in the facilitation of clinical organ transplantation, its precise mode of action remains unknown. Future experiments will be performed to clarify the mechanism of the apparent inhibition of antigen presentation function by cyclosporine. These studies should further the understanding of the mechanisms by which intracellular pathogens Listeria and fungal products (cyclosporine) regulate macrophage and lymphocyte function and how immunity to microorganisms is generated and expressed.
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