Emil R. Unanue, M.D. (Director)

DEPARTMENT OF Medical School Admin.
Paul M. Allen, Ph.D.; Kenneth M. Murphy, M.D., Ph.D.
Keywords: immunology, autoimmunity, T cells, cell biology, insulin dependent diabetes mellitus

This project is focused on examining the pathogenesis of experimental diabetic autoimmunity. Four investigators have coordinated and integrated their efforts to jointly gain an understanding of how T cells cause autoimmunity to beta cells. Drs. Emil Unanue and Osami Kanagawa have a joint project that examines the biochemical properties of the class II MHC molecule (I-Ag7) of the NOD mouse, the most important molecule required for the spontaneous development of diabetes. Their initial data indicates that I-Ag7 are weak peptide-binding class II molecules. Project I evaluates the chemistry of I-Ag7 and its binding properties and attempts to correlate these properties with T cell biology. Dr. Kenneth Murphy has been studying the molecular basis of Th1/Th2 differentiation, and has recently used another T cell receptor transgenic mouse model to follow its differentiation to Th1 or Th2 phenotype. Dr. Murphy proposes to examine the genetic basis of the response of undifferentiated T cells to Th1 or Th2 subset. He has definite evidence that unknown genes regulate the response to cytokines by altering the response to IL-12. Dr. Murphy argues that an understanding of the biology and molecular basis of T cell subset differentiation will be vital for the development and control of diabetic autoimmune reactions.