T-cell epitopes in type 1 diabetes.

Type 1 diabetes (TID) results from T-cell-mediated destruction of pancreatic b cells in genetically predisposed individuals. Autoreactive CD4(+) T helper cells and CD8(+) cytotoxic T lymphocytes (CTLs) recognize b-cell-derived peptides in the context of major histocompatibility complex class II and I molecules, respectively, in a process that terminates in b-cell death. Many peptide epitopes derived from b-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 b-cell epitopes is underscored by a study showing that in the NOD mouse monitoring of a single population of b-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 b-cell epitopes and their high-avidity analogues should have considerable implications for prediction and immunotherapy of TID.