Schistosomiasis continues to be a major parasitic disease suffered by millions of people throughout the world. The underlying potentially lethal immunopathology in schistosomiasis is a granulomatous inflammation around parasite eggs, which is mediated by the host s T cells sensitized to parasite egg antigens. The proposed studies are based on the concept that such pathogenic T cell responses are amenable to down-regulation by immunotherapy, thereby resulting in the prevention of amelioration of disease. This approach has been referred to as anti-pathology vaccine. Specific T cell hybridomas will be used as probes to identify and isolate the major sensitizing egg antigens. Antigens will be cloned and their dominant T cell epitope peptide(s) will be synthesized. The type of elicited T cell response will be characterized and the genetic restriction of the T cell response will be determined. The major schistosomal egg antigen Sm-p40 will be the subject of close analysis by investigating the interaction of its dominant epitope 13mer peptide with the MHC class II molecule I-Ak, and by assessing its intrinsic pathogenicity. A broad range of experiments will test selected strategies involving specific homologous or altered peptides for the purpose of down-regulating the pathogenic T cell response. The long-term goal of this project is the achievement of effective and lasting specific T cell tolerance by way of a suitable biological vector capable of delivering the peptides into the host suffering from, or susceptible to, disease.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Project (R01)
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Tropical Medicine and Parasitology Study Section (TMP)
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Wali, Tonu M
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Tufts University
Schools of Medicine
United States
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