HLA-DM catalytically enhances peptide dissociation by sensing peptide-MHC class II interactions throughout the peptide-binding cleft.

ABSTRACT: Human leukocyte antigen-DM (HLA-DM) is an integral component of the major histocompatibility complex class II (MHCII) antigen-processing and -presentation pathway. HLA-DM shapes the immune system by differentially catalyzing peptide exchange on MHCII molecules, thereby editing the peptide-MHCII (pMHCII) repertoire by imposing a bias on the foreign and self-derived peptide cargos that are presented on the cell surface for immune surveillance and tolerance induction by CD4⁺ T cells. To better understand DM selectivity, here we developed a real-time fluorescence anisotropy assay to delineate the pMHCII intrinsic stability, DM-binding affinity, and catalytic turnover, independent kinetic parameters of HLA-DM enzymatic activity. We analyzed prominent pMHCII contacts by differentiatin

SUBMITTER: Reyes-Vargas E 

PROVIDER: S-EPMC7062162 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature