Catch me if you can – Illuminating the onset of adaptive immunity

Eliminating infected or malignantly transformed cells are fundamental tasks of our immune system. For immune surveillance, the metastable cellular proteome is displayed as broken bits (peptides) on major histocompatibility complex (MHC) class I molecules to cytotoxic T-lymphocytes. Our knowledge about the track from the cellular proteome to the presentation of the peptidome has greatly expanded, leading to a quite comprehensive understanding of the MHC I antigen processing pathway. I will report on the mechanism of antigen selection by membrane translocation, 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 will be discussed also in the context of viral immune evasion. The work provides an integral framework for understanding the quality control of antigen selection and unveils the molecular details underlying the onset of an adaptive immune response