Molecular determinants of chaperone interactions on MHC-I for folding and antigen repertoire selection.

ABSTRACT: The interplay between a highly polymorphic set of MHC-I alleles and molecular chaperones shapes the repertoire of peptide antigens displayed on the cell surface for T cell surveillance. Here, we demonstrate that the molecular chaperone TAP-binding protein related (TAPBPR) associates with a broad range of partially folded MHC-I species inside the cell. Bimolecular fluorescence complementation and deep mutational scanning reveal that TAPBPR recognition is polarized toward the α₂ domain of the peptide-binding groove, and depends on the formation of a conserved MHC-I disulfide epitope in the α₂ domain. Conversely, thermodynamic measurements of TAPBPR binding for a representative set of properly conformed, peptide-loaded molecules suggest a narrower MHC-I specificity range

SUBMITTER: McShan AC 

PROVIDER: S-EPMC6926029 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature