MHC I assembly and peptide editing - chaperones, clients, and molecular plasticity in immunity

Peptides presented on MHC I molecules allow the immune system to detect diseased cells. The displayed peptides typically stem from proteasomal degradation of cytoplasmic proteins and are translocated into the ER lumen where they are trimmed and loaded onto MHC I. Peptide translocation is carried out by the transporter associated with antigen processing, which forms the central building block of a dynamic assembly called the peptide-loading complex (PLC). By coordinating peptide transfer with MHC I loading and peptide optimization, the PLC is a linchpin in the adaptive immune system. Peptide loading and optimization is catalyzed by the PLC component tapasin and the PLC-independent TAPBPR, two MHC I-dedicated enzymes chaperoning empty or suboptimally loaded MHC I and selecting stable peptide-MHC I complexes in …