The MHC I loading complex: a multitasking machinery in adaptive immunity

•The peptide-loading complex (PLC) has an essential function in adaptive immunity directed against infected or tumor cells.•This multitasking machinery involves a set of specialized chaperones, transporters, and receptors.•Current knowledge concerning the molecular architecture, function, and dynamics of the PLC is summarized.•The fully assembled PLC comprises one TAP heterodimer, two Tsn-ERp57, and up to two MHC I and Crt molecules.

Recognition and elimination of virally or malignantly transformed cells are pivotal tasks of the adaptive immune system. For efficient immune detection, snapshots of the cellular proteome are presented as epitopes on major histocompatibility complex class I (MHC I) molecules for recognition by cytotoxic T cells. Knowledge about the track from the equivocal protein to the presentation of antigenic peptides has greatly expanded, leading to an astonishingly elaborate understanding of the MHC I peptide loading pathway. Here, we summarize the current view on this complex process, which involves ABC transporters, proteases, chaperones, and endoplasmic reticulum (ER) quality control. The contribution of individual proteins and subcomplexes is discussed, with a focus on the architecture and dynamics of the key player in the pathway, the peptide-loading complex (PLC).