Emil R. Unanue, M.D.

DEPARTMENT OF Pathology & Immunology
Keywords: antigen presentation, autoimmunity, diabetes, microbial pathogenesis, immunology

We examine antigen processing and presentation by the antigen presenting cells (APC), and the interactions of CD4 T cells with the peptide-Major Histocompatibility complex (MHC) proteins. The MHC molecules constitute a protein system that rescues peptides from extensive intracellular degradation. The class II-MHC molecules, which we study, bind primarily to peptides derived from the vacuolar digestion of internalized proteins. The APC uses MHC-molecules to present antigenic determinants to the T cell system. We are examining the processing and the features of peptides that allow for their binding to and selection for class II-MHC molecules. For this we use the protein hen-egg white lysozyme (HEL). We are trying to identify the intracellular vesicles that contain class II-MHC and their interaction with vesicles that bear the internalized HEL. We correlate our biochemical findings with the response of T cells. At the present time we examine: the biochemistry of peptide selection, the T cell response to various peptide-MHC complexes, conformational isomers of peptide-MHC and post-translational modifications of peptides.

Two experimental models apply our experience in the analysis of peptide-MHC. We examine infections with the intracellular pathogen Listeria monocytogenes, focusing on the very early events that program both the innate and adaptive immune response.

At present, a major focus centers on the immunopathogenesis of autoimmune diabetes mellitus. Our studies on autoimmune diabetes attempting to identify the antigens from beta cells that activate both B and T cells. We combine biochemical analysis involving mass spectrometry (with Professor Gross in Chemistry) with cellular studies. Where is the antigen presentation first taking place responsible for disease initiation? Which APC present diabetogenic antigens? What are the antigens? How are the beta cells recognized and how are they affected by the immune process? Which T cells cause diabetes? These are some of the fundamental questions that are asked.