T-cell clones that can efficiently transfer diabetes to prediabetic nonobese diabetic (NOD) mice provide a powerful approach to dissecting the autoimmune disease process and for investigating immunoregulation. Diabetogenic T-cell clones carried in culture allow for detailed analysis of T-cell effector function and in vivo activity, and thus the contribution of a single clonotype to pathogenesis can be studied. As T cells comprising most or all of the repertoire in T-cell receptor transgenic (TCR-Tg) mice, diabetogenic T-cell clones have led to new variations on the NOD mouse model of autoimmune disease. T-cell clones are being used to screen peptide libraries and proteomic arrays to identify the autoantigens that drive these clones in vivo and to extend our knowledge of the processes that give rise to these antigens. With the identification of peptide agonists and natural ligands, the development of MHC-peptide multimers has been possible. These reagents can track T cells in vivo and thus provide new approaches for disease diagnosis and therapy as well as a versatile set of tools for basic research on how T cells contribute to autoimmune disease.