Multifunctional Chaperone and Quality Control Complexes in Adaptive Immunity

The fundamental process of adaptive immunity relies on the differentiation of self from nonself. Nucleated cells are continuously monitored by effector cells of the immune system, which police the peptide status presented via cell surface molecules. Recent integrative structural approaches have provided insights toward our understanding of how sophisticated cellular machineries shape such hierarchical immune surveillance. Biophysical and structural achievements were invaluable for defining the interconnection of many key factors during antigen processing and presentation, and helped to solve several conundrums that persisted for many years. In this review, we illuminate the numerous quality control machineries involved in different steps during the maturation of major histocompatibility complex class I (MHC I) proteins, from their synthesis in the endoplasmic reticulum to folding and trafficking via the secretory pathway, optimization of antigenic cargo, final release to the cell surface, and engagement with their cognate receptors on cytotoxic T lymphocytes.