It is proposed that the DQw3.2 molecules act as peptide binding molecules to trigger T cell activation which leads to destruction of Beta cells in the pancreatic islets. In this current proposal, I will focus on understanding the interaction between DQ molecules and DQ binding peptides. An in vivo binding assay will be established to examine the effect of DQalpha and DQBeta polymorphisms on DQ/peptide interactions. An M13 phage peptide binding assay will also be used to identify the binding motif of DQ binding peptides. This binding motif will be used to predict DQ-restricted T cell epitopes of potential diabetogenic autoantigens. T cell that recognize this DQ/peptide complex will be generated and characterized. My long term goals are to understand the role of DQ molecules in normal and abnormal immune responses, the signal transduction pathway after engagement of DQ/peptide and T cell receptor, and whether DQ molecules have other functional roles which differ from other class II molecules. The understanding of this mechanism will lead to design of novel specific immunotherapeutics for the treatment of autoimmune diseases.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Modified Research Career Development Award (K04)
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Allergy and Immunology Study Section (ALY)
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Hyde, James F
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Benaroya Research Institute at Virginia Mason
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