Induction of Antigen-Specific Tolerance in Autoimmune Diabetes with Nanoparticles containing Hybrid Insulin Peptides and other Neo-epitopes.

The Miller lab will be responsible for preparing the Ag-coupled and Ag-encapsulating biodegradable PLG nanoparticles to be used for tolerance induction by both the Haskins and Miller labs. The lab, in parallel with studies to be done in the Haskins lab will test tolerance induction in spontaneous T1D in both wildtype NOD mice and in the BDC2.5 and NY8.3 transgenic T cell transfer systems using the various endogenous, mimotope and hybrid diabetogenic epitopes and in the islet transplant model. The lab will be primarily responsible for determining the contributing roles role of anergy and Tregs in tolerance induced by Ag-PLG nanoparticles on activated and memory CD4 and CD8 T cells including experiments determining the role of the PD-L1/PD-1 and CTLA-4 co-inhibitory pathways in tolerance induction and maintenance.