CHARACTERIZATION OF CD4+ T CELL-INDUCING EPITOPES OF ISLETSPECIFIC GLUCOSE-6-PHOSPHATASE CATALYTIC SUBUNIT-RELATED PROTEIN (IGRP) THAT PREVENT AUTOIMMUNITY
In the NOD mouse, islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP) is an important β cell autoantigen recognized by a majority of cytotoxic CD8+ T cells. This study investigates two IGRP peptides (P3 and P7) which contain MHC class Il-specific CD4+ T cell epitopes. Amino acid residues critical for the activity of P3 and P7 were determined by deletion mapping and alanine substitutions. Binding studies indicate that the affinity of P3 and P7 peptides for I-Ag7 correlates with their ability to prevent T1D. Immunization with IGRP peptides induces the production of Th2- biased autoantibodies against the immunizing IGRP peptide and other autoantigenic epitopes. The cytokine secretion profile of IGRP peptide-primed CD4+ T cells is indicative of a heterogeneous population of regulatory cells which protect against T1D development via IL-10 and TGF-B production. The ability to induce regulatory T cells makes IGRP peptides P3 and P7 attractive targets for diabetes therapy and prevention.
Type 1 diabetes, NOD mouse, IGRP, peptide, I-Ag7, CD4+ T cells, regulatory T cells
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