Mechanism of pMHC–TCR-Induced T-Cell Activation

Determine the molecular mechanism by which binding between peptide–major histocompatibility complex (pMHC) and T-cell receptor (TCR) complexes triggers T-cell activation.

Background

T-cell activation begins when a TCR recognizes a viral or other antigenic peptide presented by an MHC molecule as a pMHC complex. Although the paper uses molecular-dynamics simulations and machine learning to identify conformational and dynamical features associated with immunogenicity, the mechanistic link between pMHC–TCR binding and initiation of the downstream T-cell response is not fully established.

Resolving this mechanism is important for understanding how selective TCR recognition produces signaling and for improving computational prediction of immunogenic viral epitopes and peptide-vaccine candidates.