Universal open MHC-I molecules for rapid peptide loading and enhanced complex stability across HLA allotypes.

ABSTRACT: The polymorphic nature and intrinsic instability of class I major histocompatibility complex (MHC-I) and MHC-like molecules loaded with suboptimal peptides, metabolites, or glycolipids presents a fundamental challenge for identifying disease-relevant antigens and antigen-specific T cell receptors (TCRs), hindering the development of autologous therapeutics. Here, we leverage the positive allosteric coupling between the peptide and light chain (β₂ microglobulin, β₂m) subunits for binding to the MHC-I heavy chain (HC) through an engineered disulfide bond bridging conserved epitopes across the HC/β₂m interface, to generate conformationally stable, peptide-receptive molecules named "open MHC-I." Biophysical characterization shows that open MHC-I molecules are p

SUBMITTER: Sun Y 

PROVIDER: S-EPMC10288639 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature