CD8+ cytotoxic T-cells are thought to be critically involved in islet destruction in type I diabetes. This work is designed to identify peptide epitopes that are recognized by islet specific CD8+ T-cells. Cloned islet specific CD8+ T-cells from the islet lymphocytic infiltrate that recognizes both islets and immortalized NIT beta cell line have been and will continue to be generated and assessed for their ability to replace CD8+ polyclonal T-cells in disease transfer experiments. MHC Class I bound peptides will be isolated from NIT-cells as will a subset that is recognized by CD8+ T-cell clones.
In Specific Aim 2 the peptides will be tested for their ability to stimulate disease producing CD8+ T-cells. Synthetic peptides derived from the sequence of known beta cell autoantigens will also be tested.
In Aim 3 how cytokines and glucose induced beta cell secretory activity influence presentation of peptides and susceptibility to killing by CD8+ T-cells will be examined.
