Onur Serçinoğlu
Turkish Journal of Immunology - 2025;13(3):132-145
Objective: The dynamic interaction between peptide ligands and major histocompatibility complex (MHC) molecules plays a critical role in regulating cytotoxic T-cell response. While peptide-free MHC molecules are known to be highly unstable, the precise mechanisms un- derlying peptide-induced stabilization remain poorly understood. Materials and Methods: Classical molecular dynamics simulations of human leukocyte an- tigen (HLA)-A*02:01 in both peptide-free and peptide-bound states were performed. Each simulation was conducted in triplicate to ensure reproducibility. Protein energy networks were constructed using pairwise amino acid interaction energies computed from resulting trajectories. Network analysis was performed to reveal the roles of residues in protein sta- bility. Results: The analysis revealed that peptides with weak interactions at the F pocket failed to enhance connectivity at the HLA-beta2m interface, thereby compromising the overall structural stability of peptide-loaded MHC (pMHC). Conclusion: These findings shed light on the mechanisms by which peptides stabilize MHC molecules and modulate their dynamics, providing insights into T-cell receptor recognition and the regulation of immune responses.
