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The endogenous antigen processing and presentation (APP) is a fundamental pathway found in jawed vertebrates, which allows for a set of epitope peptides sampled from the intracellular proteome to be assembled and displayed on class I proteins of the major histocompatibility complex (MHC-I). Peptide/MHC-I antigens enable different aspects of adaptive immunity to emerge, by providing a basis for recognition of self vs. non-self by T cells and Natural Killer (NK) cells. Pioneering studies of pMHC-I molecules and their higher-order protein complexes with molecular chaperones and membrane receptors have gleaned important insights into the peptide loading and antigen recognition mechanisms. While X-ray and cryoEM structures have provided us with static snapshots of different MHC-I assembly stages, complementary bio…