The recognition of a peptide-major histocompatibility complex (pMHC) by its cognate T cell receptor (TCR) plays a central role in governing the immunogenic outcome. As such, understanding the structural and biophysical parameters of the pMHC-TCR interaction are critical for explaining, or predicting, the immunogenicity of specific peptide epitopes or MHC alleles. For example, pMHC stability, peptide-loading capacity, propensity for catch-bond formation, interaction free energy, and interface dynamics have all been linked to enhanced, or decreased, immunogenicity for specific pMHC-TCR pairings. Specifically, interface dynamics have become an area of increased interest with the increasing accessibility to longer molecular dynamic simulations and high-quality NMR spectra of pMHC molecules. We are particularly interested in the dynamic perturbations that occur upon the introduction of diQerent peptide variants or MHC mutations. In this regard, our project will assess the interface dynamics of several related murine and human pMHCs both with and without the presence of a TCR. We will use a combination of established unbiased and umbrella- sampled MD simulations to obtain trajectories encoding dynamic information over 100s of ns. These obtained trajectories can then be further analyzed through a range of structure- based computational methods to extract the residue-based dynamic coupling throughout the interface.