T cell activation requires that the immunogen be presented in association with a major histocompatibility complex (MHC) class II molecule. Our long-term objective is to understand how antigen presentation in the context of self applies to alloimmune (transplantation) responses and, given the rich array to human class II molecules, which ones are used for which functions. We will use serologic, cellular, and molecular in approaches to pursue our objective. We will define epitopes of MHC molecules in structural terms using haplotypes with unusual linkage disequilibria and varient alleles that we have identified in different ethnic populations. The epitopes will be defined serologically, using allo- and monoclonal antibodies, and molecularly usng restriction endonucleases and genetic probes, to map and sequence gene segments. Epitopes of MHC molecules will also be investigated for their ability to serve as restriction elements for foreign antigen presentation to T lymphocytes. We will investigate the ability of certain mediators of gene expression to alter differentially the profile of MHC antigen expression and will analyze mechanisms involved in gene regulation of this expression. Lastly, we will investigate genetic basis for disease susceptibility in polyglandular failure disease, hodgkin's disease and type II diabetes using serologic and molecular probes.
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