“Catch me if you can – illuminating the onset of adaptive immunity”

Identifying and eliminating infected or malignantly transformed cells are fundamental tasks of the adaptive immune system. For immune surveillance, the metastable cellular proteome is displayed as broken bits (peptides) on major histocompatibility (MHC) class 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 MHC I antigen processing pathway. I will report on the structure and mechanism of antigen translocation, editing and proofreading. 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. The mechanisms of viral immune evasion will also be addressed. 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.