Pathogenesis of NOD diabetes is initiated by reactivity to the insulin B chain 9-23 epitope and involves functional epitope spreading

► InsB9-23 appears to be the initiating diabetogenic epitope in T1D in the NOD mouse. ► Progression of T1D in NOD mice is driven by epitope spreading. ► Ag-SP tolerance can be employed to both prevent and treat T1D in the NOD mouse. ► Ag coupled to RBCs can also be used to induce tolerance in T1D in the NOD mouse.