Prediction of spontaneous autoimmune diabetes in NOD mice by quantification of autoreactive T cells in peripheral blood

Autoimmune (type 1) diabetes mellitus results from the destruction of insulin-producing pancreatic beta cells by T lymphocytes. Prediction of cell-mediated autoimmune diseases by direct detection of autoreactive T cells in peripheral blood has proved elusive, in part because of their low frequency and reduced avidity for peptide MHC ligands. We demonstrate here that MHC class I tetramers complexed to a high-avidity analogue of an immunodominant P cell epitope detect diabetogenic CD8(+) T cells in the peripheral blood of NOD mice ex vivo and that the quantification of this autoreactive T cell population in peripheral blood is a powerful predictor of autoimmune diabetes.