Tetramer technology used to enumerate a diabetogenic CD4⁺ T cell clonotype (designated BDC2.5) in autoimmune diabetes–prone NOD mice. A mimotope peptide structurally similar to the native peptide antigen processed from a pancreatic β cell granule protein is presented by the NOD H2-A^g7 MHC class II molecule (a). The MHC class II α chain is depicted in green, the β chain in blue, and the mimotope peptide in grey/red space fill representation. The α chain of the peptide-associated H2-A^g7 complexes are biotinylated, allowing tetramer formation by binding four such molecules to streptavidin (b). Such a reagent allows detection of T cells with the BDC2.5 specificity in the anatomical site of choice (c). Tetramer crystal structure courtesy of Luc Teyton (The Scripps Research Institute, La Jolla, California, USA).