Structure and mechanism of MHC I chaperone and peptide-loading complexes illuminate the onset of adaptive immunity

Identifying and eliminating infected or malignantly transformed cells are fundamental tasks of our adaptive immune system. For immune surveillance, the cell’s metastable proteome is displayed as broken bits (peptides) on major histocompatibility complex class I (MHC I) molecules to cytotoxic T-lymphocytes. Our knowledge about the track from the proteome to the presentation of peptides has greatly expanded, leading to a quite comprehensive understanding of the antigen processing pathway. I will report on the mechanism of antigen translocation, chaperoning, editing, and final quality control. Based on an integrative approach, the contribution of individual proteins as well as the architecture of the MHC I peptide-loading complex (PLC) and other MHC I editing complexes, also in the context of viral immune evasion, will be addressed. The work provides the framework for understanding the quality control of antigen selection and unveils the molecular details underlying the onset of an adaptive immune response.