T cells play a key role in the immune destruction of pancreatic islet-cells that leads to type 1 insulin dependent diabetes mellitus (IDDM). The antigens, and T cell subsets responsible for the autoreactivity have, however, remained unclear. The present proposal aims to study T cell reactivity to a prominent ,B-cell autoantigen, glutamic acid decarboxylase (GAD). The goal is to characterize which factors determine whether a Thl or Th2 type response to GAD becomes dominant, and which of these subsets is responsible for the immunopathogenesis of the disease. Thl and Th2 type responses will be examined by measuring cytokine production of peripheral blood lyrnphocytes from diabetics and prediabetics. These data will then be correlated with clinical and immunogenetic profile of the patients. Different antigenic peptides of GAD will also be studied for their ability to elicit Thl or Th2 cell responses. The results obtained will lead to improved understanding of the induction of the autoimmune process leading to IDDM, and help in the search for means to prevent the onset of clinical disease.