Regulation of the cellular trafficking of TAPBPR and its implication on MHC class I peptide presentation (360G-Wellcome-109076_Z_15_A)

The process of antigen presentation by major histocompatibility complex (MHC) class I molecules is a crucial process in protecting the human body against intracellular infections and cancer. These molecules present the cellular proteome, in form of short peptides, at the cell surface, for the inspection by cytotoxic T lymphocytes. The MHC class I molecules acquire their peptides in the ER, a process facilitated by the peptide loading complex (PLC). As part of the PLC, tapasin was until recently believed to be the only MHC class I specific chaperone directly involved in peptide selection. However, that has changed with the Boyle laboratory's discovery that a protein called TAPBPR is a second MHC class I dedicated chaperone, intimately involved in peptide selection. It is now essential to understand the distinct roles of the two MHC class I dedicated chaperones and how they work together in determining the final peptide repertoire displayed to the immune system. My key research goals are to investigate how the cellular trafficking of TAPBPR influences its effects on class I antigen presentation and what are the cellular factors that control its trafficking.