Structure and Function of Molecular Chaperones that Govern Immune Peptide Loading.

Abstract

Major histocompatibility class I (MHC-I) molecules bind peptides derived from cellular synthesis and display them at the cell surface for recognition by receptors on T lymphocytes (TCR) or natural killer (NK) cells. Such recognition provides a crucial step in autoimmunity, identification of bacterial and viral pathogens, and anti-tumor responses. Understanding the mechanism by which such antigenic peptides in the ER are loaded and exchanged for higher affinity peptides onto MHC molecules has recently been clarified by cryo-EM and X-ray studies of the multimolecular peptide loading complex (PLC) and a unimolecular tapasin-like chaperone designated TAPBPR. Insights from these structural studies and complementary solution NMR experiments provide a basis for understanding mechanisms related to immune antigen presentation.