Type 1 diabetes (TID) results from T-cell-mediated destruction of pancreatic ß cells in genetically predisposed individuals. Autoreactive CD4⁺ T helper cells and CD8⁺ cytotoxic T lymphocytes (CTL_s) recognize ß-cell-derived peptides in the context of major histocompatibility complex class II and I molecules, respectively, in a process that terminates in ß-cell death. Many peptide epitopes derived from ß-cell proteins have been described for both humans and the nonobese diabetic (NOD) mouse, but their relative importance in disease pathogenesis is unclear. The significance of identifying key ß-cell epitopes is underscored by a study showing that in the NOD mouse monitoring of a single population of ß-cell-specific CTLs in the peripheral blood using a high-avidity analogue of the endogenous peptide may be used to accurately predict diabetes occurrence. Future studies focused on the discovery of immunodominant ß -cell epitopes and their high-avidity analogues should have considerable implications for prediction and immunotherapy of TID.