Our immune system works tirelessly to identify and fight off harmful pathogens and cancer cells. When cells become diseased, they display antigens on their surface as signals for the immune system. To better understand how antigens are processed and transported in real-time, scientists have created a light-responsive ‘cage’ that can release trapped antigens at specific times and places.
Our immune system is constantly vigilant, recognizing and eliminating pathogens and cancer cells. Diseased cells present antigens on their surface as signals for the immune system. To study the complex processes involved in antigen processing and transport, a German research team has developed a light-triggered ‘cage’ that can release antigens at precise times and locations, as published in the journal Angewandte Chemie.
Within our cells, proteins, both from our own body and foreign sources, are broken down into smaller fragments and transported to the endoplasmic reticulum (ER), a network of channels within a membrane, by a transporter known as the transporter associated with antigen processing (TAP). Here, the peptide loading complex (PLC) regulates the loading of MHC I (major histocompatibility complex class I) with antigenic peptides. Certain peptides are preferentially loaded onto MHC I, undergo further processing for immune surveillance, and are presented on the cell surface. Peptides from normal proteins generally go unnoticed by the immune system unless there are autoimmune reactions.
Despite advancements in our understanding, many details regarding antigen translocation, PLC assembly, and the interaction between PLC subunits in maintaining the quality of peptide-MHC complexes are still unclear. To delve deeper into antigen processing, researchers like Ralph Wieneke and Robert Tampé from the University of Frankfurt am Main in Germany have developed a system that releases antigens in response to light stimulation, allowing precise study of antigen movement. By releasing antigens from an ‘inactive’ state using light, this method offers controlled and non-invasive analysis in living cells.
The research team used a peptide from an HIV antigen for their experiments. They linked the peptide epitope to biotin and then to a protein named streptavidin. In this configuration, the epitope is shielded from recognition by the antigen processing transporter (TAP). With a light-sensitive group in the linker, exposure to UV light causes the peptide epitope to be released, recognized by TAP, and transported across the ER membrane for loading onto MHC I by the PLC.
This approach is versatile and has been applied in various scenarios, such as tracking antigen movement by TAP within the ER membrane of human lymphoma cells. Wieneke and Tampé aim to use this light-activated system to study the antigen processing pathway across different cell compartments, providing insights into the dynamics of immune processes in vivo.
