Research Focus


Welcome to the Emil R. Unanue-

Javier A. Carrero Laboratory

 

The long-term goal of the laboratory is to understand antigen presentation, both at the cellular and biochemical level, and to correlate antigen presentation events to the response of CD4 T lymphocytes. Our current focus is entirely on the autoimmune diabetes in the non-obese diabetic (NOD) mouse. We combine biochemical and biological parameters related to antigen selection, recognition and processing by antigen presenting cells (APC). We examine antigen presentation and the antigen presenting cells in the islets of Langerhans of the non-obese diabetic mouse. We want to identify the earliest events in autoimmunity in this confined tissue, and we believe the resident APCs are integral players in this early process. Islets normally have a population of macrophages that is distinct from those that inhabit the exocrine pancreas. In addition, the islets of the NOD mouse strain contain is a minor population of dendritic cells (DC) that bear the CD103 integrin. We find close interactions between beta cells and the two APCs that result in the initiation of autoimmunity. Even under non-inflammatory conditions, beta cells transfer insulin-containing vesicles to the APCs of the islet. This reaction requires live cells and intimate contact. The autoimmune process starts in islets with the entrance of CD4+ T cells and an increase in the CD103+ DCs. Mice deficient in the Batf3 transcription factor never develop diabetes due to the absence of the CD103/CD8α lineage of DCs. We hypothesize that the 12-20 peptide of the beta chain of insulin is responsible for activation of the initial CD4+ T cell response during diabetogenesis. We are always looking for talented graduate students and post-docs interested in studying the nuances of autoimmune disease initiation.



A brief history of the accomplishments of our laboratory was published in Nature Immunology, 7: 1277-1279, 2006: "From antigen processing to peptide-MHC binding". See also "Making antigen presentable" by Paul Allen in J Immunol, 179: 3-4, 2007; "Studies with Listeria monocytogenes lead the way" in Adv Immunol 2012;113:1-5; Antigen presentation events in autoimmune diabetes: Curr Opin Immunol 2011;24:1-10. A recent chapter in Ann Rev Path (2011;6:1-8) traces Emil's entry into immunology: "Starting immunology by way of immunopathology".