Research

Antigen presentation represents a unique cell biological process that bases construction and effectuation of adaptive immunity. This process is mediated by a handful of cell types equipped with specific molecules including major histocompatability complex (MHC) and costimulatory molecules. Our laboratory is interested in understanding the mechanisms by which the antigen presentation mediated by MHC class II molecule contributes to the development, activation, and regulation of adaptive immunity comprised of activation of T and B cells. Current research is focused on identifying the role of a protein named MARCH1 (Membrane-Associated RING-CH1) in antigen presenting function of dendritic cells. MARCH1 is a ubiquitin ligase expressed in dendritic cells, B cells, and macrophages. This enzyme attaches a ubiquitin chain to the cytoplasmic tail of MHCII and the costimulatory molecule CD86 and mediate internalization and lysosomal degradation of these molecules. However, the functional role of this ubiquitination is not clearly understood. For the past several years, we have investigated whether MARCH1 plays any important role in the development of T cells. This study has revealed that MARCH1 is essential for thymic dendritic cells to mediate the development of natural regulatory T cells and that this role is critically dependent on MHCII ubiquitination. We have recently expanded our study to the examination of the role of MARCH1 in peripheral immune responses using mouse models of microbial infection, allergic asthma, and auto-immune diseases. We hope this study will shed additional light on the functional role of MARCH1 and create a novel therapeutic opportunity to control antigen presenting cell function for treatment of immune-mediated diseases.