Project 18

Protein assemblies and machineries in antigen processing and ER quality control

Principle Investigator: Prof. Dr. Robert Tampé

Research Areas: Membrane biochemistry and biophysics, structural biology

Summary

The adaptive immune system is built on sophisticated interplay of intracellular pathways and machineries of modularization, compartmentalization, and confinement. By monitoring peptide-MHC complexes, T-lymphocytes are able to identify and eliminate infected and cancerous cells. Stringent assembly of peptide-MHC I complexes occurs in a multitasking machinery, the MHC peptide-loading complex (PLC), in which the ABC transporter associated with antigen processing (TAP) shuttles proteasomal degradation products into the endoplasmic reticulum, resulting in the assembly and peptide loading of MHC I. Given their fundamental role within the immune system, these membrane-based assemblies are attractive targets for strategy development of viruses seeking to evade immune surveillance. Despite significant breakthroughs in elucidating the architecture of the multicomponent PLC and related quality control machineries, their mechanistic principles, dynamic assembly, and supramolecular organization remain to be adequately defined. By integrative biochemical and biophysical approaches, we will unravel how these immune service machineries operate temporally and spatially, and how viral factors come to modulate their function, supramolecular assembly and networking within membranes.