Cellular Machineries in Antigen Processing and Recognition

To elicit an effective immune response against pathogens and cancerous cells, major histocompatibility complex class I (MHC I) molecules undergo a complex journey from their biogenesis in the ER to their final decoding by cytotoxic T cells on target cell surfaces. Cellular machinery, consisting of membrane transporters, several chaperones, and receptors, facilitates MHC I assembly, quality control, and final recognition of peptide-MHC I. However, the mechanistic integration of these processes remains poorly understood. I will discuss the multichaperone-client interaction network of the MHC I peptide loading complex assembled on the ABC transporter associated with antigen processing. Using integrative approaches, we reveal the mechanistic underpinnings of antigen transport, epitope proofreading, quality control, and the final release of MHC I complexes. Additionally, I will present structural and mechanistic insights into the T cell receptor complex bound to a tumor-specific human class I pMHC. The T cell receptor complex is most fascinating due to its extraordinary ability to specifically recognize a vast array of antigens and its enigmatic signaling mechanisms that enable precise and highly regulated immune responses against cancer and pathogens.