This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Type 1 diabetes mellitus is a T cell-mediated autoimmune disorder that results in the destruction of insulin-producing pancreatic islet ¿ cells. The class II MHC molecules are the single-most important genetic element that predispose to onset of diabetes. Our previous work has defined the biochemical and structural features of the murine diabetogenic class II MHC molecule, I-Ag7, and its human counterpart, HLA-DQ8. We have now built upon this work to engineer islet ¿ cell tumor lines that express I-Ag7 and are able to activate diabetogenic T cells isolated from infiltrated pancreas of experimental mice. The future experiments are focused on using mass spectrometry to identify I-Ag7-bound peptides that activate autoreactive T cells. A second and related aim is to identify the entire spectrum of islet ¿ cell-specific peptides and use these as probes to evaluate the repertoire of T cells that maybe directed against these ligands.