This award will aid in the principal investigator's shift of research focus from basic immunology and immunogenetics to the genetics and pathogenesis of insulin-dependent diabetes (IDDM). The goal of the current project is to identify new genetic markers that, singly or in combination with other markers, more precisely define the IDDM-susceptible genotype. We hope in this way to better identify persons genetically susceptible to IDDM, so that preventive measures can be properly focused. To acomplish this, we have initiated studies using Primed Lymphocyte Typing (PLT) with human T lymphocyte clones. In PLT, a technique developed by the principal investigator, T. lymphocytes of donor A are "primed" in vitro by exposure to x-irradiated leukocytes from a second donor, B, and stored frozen. When thawed, the primed cells proliferate rapidly (assayed by tritiated thymidine incorporation) if exposed to cells sharing Class II HLA antigens with B. We have applied PLT to diabetes by choosing donor B to be an IDDM patient and donor A to be a person with no family history of diabetes. So far, these studies have yielded three clones of interest: two detecting a new Class II HLA antigen, B01, that may mark a subset of HLA-DR3 haplotypes with increased risk for IDDM, and one detecting HLA-Dw10, which we find to be strongly associated with IDDM among Ashkenazi Jews. Our specific aims are to: 1. Explore further the relationship of the B01 antigen to IDDM, 2. Confirm the association of HLA-Dw10 with IDDM in Ashkenazi Jews, 3. Produce at least 50 additional T-cell clones detecting non-HLA-DR leukocyte antigens of IDDM patients, and 4. Determine the relationship of these non-DR antigens to known Class II antigens and to IDDM.