The primary interest of this laboratory is in the control by genes of the major histocompatibility complex (MHC) of immune functions and in the role that MHC genes have in the pathogenesis of autoimmune diseases. Projects have dealt with MHC gene influence on NK cell repertoire, T cell antigen receptor repertoire and the human immune response, on immunoglobulin deficiencies, on autoimmune diseases, and on dendritic cell surface molecules and function. We have examined genetic determination of the human immune response to the hepatitis B vaccine and tetanus toxoid peptides, using these as models. Because incomplete pentrance of susceptibility genes is characteristic of MHC-associated phenomena, including diseases such as type diabetes (T1D), gluten-sensitive enteropathy and IgA deficiency, we have been exploring the role of MHC gene expression in determining penetrance. We have developed ways to analyze modes of inheritance of incompletely penetrant MHC traits and of localizing, identifying and determining modes of inheritance of specific MHC susceptibility genes. We are currently focusing our efforts on type 1 diabetes.