A short HLA-DRA isoform binds the HLA-DR2 heterodimer on the outer domain of the peptide-binding site.

ABSTRACT: The human leukocyte antigen (HLA) locus encodes a large group of proteins governing adaptive and innate immune responses. Among them, HLA class II proteins form α/β heterodimers on the membrane of professional antigen-presenting cells (APCs), where they display both, self and pathogen-derived exogenous antigens to CD4⁺ T lymphocytes. We have previously shown that a shorter HLA-DRA isoform (sHLA-DRA) lacking 25 amino acids can be presented onto the cell membrane via binding to canonical HLA-DR2 heterodimers. Here, we employed atomistic molecular dynamics simulations to decipher the binding position of sHLA-DRA and its structural impact on functional regions of the HLA-DR2 molecule. We show that a loop region exposed only in the short isoform (residues R69 to G83) is responsible f

SUBMITTER: Shams H 

PROVIDER: S-EPMC9007275 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature