Disabling a CD8+ epitope. Intranasal administration of different proinsulin peptides results in presentation from an antigen-presenting cell (APC) to CD4+ and CD8+ T cells, depending on the peptide administered. Proinsulin peptides B24–C36, B24–C35, and B26–C34 can bind to the MHC class I molecule (Kd), resulting in the activation of cytotoxic T cells. The use of truncated peptides that do not contain the residues critical for binding to Kd, but still bind to the NOD mouse MHC class II molecule (I-Ag7), allows for selective activation of regulatory CD4+ T cells. The same APC is shown presenting simultaneously to both CD4+ and CD8+ T cells for illustration purposes. TCR, T cell receptor.