Antigen Delivery Controlled by an On-Demand Photorelease

To eliminate infected and cancerous cells, antigen processing and presentation play a pivotal role through the recognition of antigenic peptides displayed on Major Histocompatibility Complex class I (MHC I) molecules. Here, we developed a photostimulated antigen release system that enables the temporal inception of antigen flux. Simple and effective photocaging of the human immunodeficiency virus (HIV)-Nef73-derived epitope, a representative high-affinity MHC I ligand, was provided by steric hindrance to block the recognition by the transporter associated with antigen processing (TAP) in the peptide loading complex (PLC). In response to light, a heteronomous release of antigens and subsequent translocation in various scenarios is demonstrated, including a TAP-related ATP-binding cassette (ABC) transporter reconstituted in liposomes and the native PLC in the endoplasmic reticulum (ER) membrane of human cells. The photochemically induced ‘burst’ of antigens opens new prospects for a mechanistic analysis of the antigen translocation machinery and will help to provide insights into antigen processing pathways via an on-demand, subcellular pulse-chase release of antigens.