The goal of the proposed research is to investigate the nature of molecules on the surface of islet cells that may be antigenic in the pathogenesis of Type I Diabetes. It is not known whether the islet cell antigen is a normal product of the beta cell or whether it is the result of an environmental agent, such as a virus. The hypothesis to be tested in this project is that the antigen is a molecule normally present on islet beta cells.
The specific aims of this project are: 1. Develop antibodies to islet cells by induction of diabetes in autoimmune mice using the diabetogenic drug, streptozotocin, and by selection of auto-antibodies to islets in the diabetic NOD mouse. Mice judged to be making antibodies to islet cells will be used in the production of monoclonal antibodies. 2. Characterize monoclonal antibodies obtained in Specific Aim No. 1 with regard to the molecules they recognize on islet cells. The antibodies will be defined by their ability to bind islet cells, by the products they immunoprecipitate from islet cells, and by their ability to affect disease transfer or graft rejection experiments. 3. Develop T cell lines specific for islet cells by isolating T cells primed for islet antigens. These cells would be obtained from spleen and/or lymph node cells of diabetic mice or from grafts of islet tissue in diabetic mice. T cells from these sources that proliferate in response to islet antigen and antigen-presenting cells will be used to established permanent lines of islet-specific T cells.
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