Dynamical network analysis reveals long-range residue couplings at the pMHC interface underlying enhanced immunogenicity.

ABSTRACT: The interaction between a class I peptide-major histocompatibility complex (pMHC) and a T cell receptor (TCR) plays a central role in the elicitation of CD8⁺ T cell immune responses. As a result, considerable effort has been invested in understanding the structural, dynamic, and biophysical parameters that govern this recognition event, including designing altered peptide ligands (APLs) which seek to modulate the downstream signaling outcomes. However, dynamic links between modified peptide positions and distant residues have remained ill resolved until now. Using an integrative approach combining crystallographic ensemble and single models with atomistic molecular dynamics simulations and correlational analysis, we have established an approach that allows us to identify coupled

SUBMITTER: Resink T 

PROVIDER: S-EPMC12855856 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature