The Evolution of HLA-B ^*3501 Binding Affinity to Variable Immunodominant NP _418-426 Peptides from 1918 to 2009 Pandemic Influenza A Virus: A Molecular Dynamics Simulation and Free Energy Calculation Study

Virus-specific cytotoxic T lymphocytes contribute to the control of virus infections including those caused by influenza viruses. However, during the evolution of influenza A viruses, variations in cytotoxic T lymphocytes epitopes have been observed and it will affect the recognition by virus-specific cytotoxic T lymphocytes and the human virus-specific cytotoxic T lymphocytes response in vitro. Here, to gain further insights into the molecular mechanism of the virus-specific cytotoxic T lymphocytes immunity, the class I major histocompatibility complex-encoded HLA-B ^*3501 protein with six different NP _418-426 antigenic peptides emerging from 1918 to 2009 pandemic influenza A virus were studied by molecular dynamics simulation. Dynamical and structural properties (such as atomic fluctuations, solvent-accessible surface areas, binding free energy), based on the solvated protein-peptide complexes, were compared. Free energy calculations emphasized the important role of the secondary anchors (positions 2 and 9) in influencing the binding of MHC-I with antigenic non-apeptides. Furthermore, major interactions with peptides were gained from HLA-B ^*3501 residues: Tyr7, Ile66, Lys146, Trp147, and Tyr159. Detailed analysis could help to understand how different NP _418-426 mutants effectively bind with the HLA-B ^*3501.