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.
Jingjing
J
Guo
Xiaoting
X
Wang
Huijun
H
Sun
Huanxiang
H
Liu
Yulin
Y
Shen
Xiaojun
X
Yao
D000595:Amino Acid Sequence; D001665:Binding Sites; D019143:Evolution, Molecular; D015797:HLA-B35 Antigen / Q000378:metabolism*; D049673:History, 20th Century; D049674:History, 21st Century; D006801:Humans; D006860:Hydrogen Bonding; D009980:Influenza A virus / Q000378:metabolism*; D007251:Influenza, Human / Q000453:epidemiology / Q000266:history; D056004:Molecular Dynamics Simulation; D009154:Mutation; D009698:Nucleoproteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D058873:Pandemics; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D013816:Thermodynamics
C500431:HLA-B*35:01 antigen; D015797:HLA-B35 Antigen; D009698:Nucleoproteins