Trypanosoma cruzi infects a broad range of mammalian species. The infection causes a chronic inflammatory process, and Chagas Disease in humans. Surface proteins of the parasite interact with mammalian host cells, and are thought to participate in adhesion invasion, and perturbation of these cells. A detailed molecular understanding of the surface proteins is critical to developing methods to interfere with the infectious process. The major surface proteins of T. cruzi have an approximate molecular weight of 85-kD. The SA85-1 family (surface antigens, 85kD) is part of this major grouping of 85-kD proteins. Each SA85-1 protein appears to be simultaneously expressed by each parasite in a population, and has homology to sialidases. Yet the SA85-1 proteins lack intrinsic sialidase activity. An understanding of the function of these proteins is unclear. Using molecular and cellular approaches, the preliminary data presented here continues to characterize the SA85-1 proteins, and to explore their function. Anti-SA85-1 monoclonal antibodies, and purified SA85-1 proteins from eukaryotic expression systems have been obtained. Experiments with the purified proteins indicate that one SA85-1 protein binds to cells of the skin and peripheral lymph node. These cells may be a subset of macrophages. This application proposes to utilize the monoclonal antibodies to study the expression pattern of SA-85-1 proteins, and to further characterize post- translational modifications of the SA-85-1 proteins. The proposal will also identify mammalian cells which adhere to purified SA-85-1 proteins. These adhesion experiments will be supplemented with studies which examine the interaction of parasites and mammalian cells during the acute infection. Biochemical and molecular experiments will characterize the interaction of SA85-1 proteins and mammalian cell ligands. The goal of these studies is to better understand: 1) the structure of SA85-1 proteins; 2) the expression pattern of SA85-1 proteins; and 3) the adhesive properties of the SA85-1 proteins.
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