5WWU

Crystal Structure of HLA-A*2402 in complex with 2009 pandemic influenza A(H1N1) virus and avian influenza A(H5N1) virus-derived peptide H1-25

Summary for 5WWU

• Entry DOI: 10.2210/pdb5wwu/pdb
• Related: 5WWI 5WWJ
• Descriptor: HLA class I histocompatibility antigen, A-24 alpha chain, Beta-2-microglobulin, LEU-TYR-LYS-LYS-LEU-LYS-ARG-GLU-ILE-THR-PHE (3 entities in total)
• Functional Keywords: hla-a*2402, h1n1, h5n1, h1-25, immune system
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 3
• Total formula weight: 44742.84

Authors

Zhao, M.,Liu, K.,Chai, Y.,Qi, J.,Liu, J.,Gao, G.F. (deposition date: 2017-01-05, release date: 2018-01-17, Last modification date: 2024-11-06)

Primary citation

Zhao, M.,Liu, K.,Luo, J.,Tan, S.,Quan, C.,Zhang, S.,Chai, Y.,Qi, J.,Li, Y.,Bi, Y.,Xiao, H.,Wong, G.,Zhou, J.,Jiang, T.,Liu, W.,Yu, H.,Yan, J.,Liu, Y.,Shu, Y.,Wu, G.,Wu, A.,Gao, G.F.,Liu, W.J.
Heterosubtypic Protections against Human-Infecting Avian Influenza Viruses Correlate to Biased Cross-T-Cell Responses.
Mbio, 9:-, 2018

PubMed Abstract: Against a backdrop of seasonal influenza virus epidemics, emerging avian influenza viruses (AIVs) occasionally jump from birds to humans, posing a public health risk, especially with the recent sharp increase in H7N9 infections. Evaluations of cross-reactive T-cell immunity to seasonal influenza viruses and human-infecting AIVs have been reported previously. However, the roles of influenza A virus-derived epitopes in the cross-reactive T-cell responses and heterosubtypic protections are not well understood; understanding those roles is important for preventing and controlling new emerging AIVs. Here, among the members of a healthy population presumed to have previously been infected by pandemic H1N1 (pH1N1), we found that pH1N1-specific T cells showed cross- but biased reactivity to human-infecting AIVs, i.e., H5N1, H6N1, H7N9, and H9N2, which correlates with distinct protections. Through a T-cell epitope-based phylogenetic analysis, the cellular immunogenic clustering expanded the relevant conclusions to a broader range of virus strains. We defined the potential key conserved epitopes required for cross-protection and revealed the molecular basis for the immunogenic variations. Our study elucidated an overall profile of cross-reactivity to AIVs and provided useful recommendations for broad-spectrum vaccine development. We revealed preexisting but biased T-cell reactivity of pH1N1 influenza virus to human-infecting AIVs, which provided distinct protections. The cross-reactive T-cell recognition had a regular pattern that depended on the T-cell epitope matrix revealed via bioinformatics analysis. Our study elucidated an overall profile of cross-reactivity to AIVs and provided useful recommendations for broad-spectrum vaccine development.

PubMed: 30087171
DOI: 10.1128/mBio.01408-18

Experimental method

X-RAY DIFFRACTION (2.794 Å)