Endothelial Antigen Presentation

Our group is interested in characterizing potentially critical, but poorly understood, contribution of endothelium to antigen (Ag)-specific immunity and pathologies such as allograft rejection, myocarditis, vasculities, diabetes, lupus and multiple sclerosis. Besides the canonical ‘professional’ Ag Presenting Cells (APCs; e.g., dendritic cells), endothelial cells are one of the few cell types that express both Major Histocompatibility Complex (MHC)-I and –II along with co-stimulatory molecules, which are necessary to present peptide Ag to CD8+ and CD4+ T cells. We and others have shown that endothelium can activate previously primed CD8+ and CD4+ T cells (but not naïve T cells) in an Ag-specific manner, through a novel ILP enriched immunological synapse (a ‘Podo-Synapse’). Thus the endothelium may play unique roles as ancillary or ‘semi-professional’ APCs that function during the effector phase of immune responses.

Our ongoing studies seek to determine specific contributions of the endothelium to Ag-specific immunity mediated by CD4+ and CD8+ T cells in vivo through new endothelial-specific knockout strains of Ag presentation molecules that we have developed. We are also exploring how MHC-related proteins expressed on endothelial surfaces, may analogously instruct Natural Killer (NK) and NKT cells.