rmyates [at] ucalgary [dot] ca
Macrophages and dendritic cells (DCs) are phagocytic antigen presenting cells (APCs) of the mammalian immune system. The phagosome and endosome are intracellular organelles that are formed following phagocytosis and endocytosis of exogenous material by these cells. The lumen of these organelles is critical to the acquired immune response as it is the site of processing of exogenous antigen. In order for complex protein antigens to be presented to T cells, they must first be proteolytically processed within these microenvironments into small linear oligopeptides. These can then be loaded directly onto MHC-II molecules or exported to the cytoplasm for additional processing for MHC-I presentation (“cross presentation”). The chemistries within the phagosome and endosome affect both the generation efficiency and the repertoire of presentable oligopeptides. My lab over the past three years has been studying the microenvironment of phagosomes and endosomes. The overall mission of our research program is to understand how antigen processing is controlled and modulated by microenvironmental parameters in the phago/endosomes of antigen presenting cells. We further aim to exploit this knowledge to manipulate antigenic peptide repertoires, in order to enhance prevention and management strategies for specific disease states. More recently, we have become invested in applying our basic findings to investigate manipulation of T cell populations in models of Multiple Sclerosis (MS). Our ultimate goal will be to identify agents that are able to manipulate antigen processing in MS, so as to decrease the generation of key peptides responsible for the initiation and maintenance of autoreactivity. This applied portion of the research program is being conducted in collaboration with Dr. Frank Jirik and is funded by the Multiple Sclerosis Society of Canada (MSSOC), with in-kind support from the EndMS foundation of Alberta. We hope to become more integrated and active within the HBI MS program.