4F7T

Crystal Structure of HLA-A*2402 Complexed with a Newly Identified Peptide from 2009 H1N1 PB1 (498-505)

4F7T の概要

• エントリーDOI: 10.2210/pdb4f7t/pdb
• 関連するPDBエントリー: 3I6L 4F7M 4F7P
• 分子名称: HLA class I histocompatibility antigen, A-24 alpha chain, Beta-2-microglobulin, RNA-directed RNA polymerase catalytic subunit, ... (4 entities in total)
• 機能のキーワード: hla-a*2402, 2009h1n1, hla-a3 supertype, cross-allele recognition, immune system
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Membrane; Single-pass type I membrane protein: P05534; Secreted: P61769
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 89073.07

構造登録者

Liu, J.,Zhang, S.,Tan, S.,Yi, Y.,Wu, B.,Zhu, F.,Wang, H.,Qi, J.,Gao, G.F. (登録日: 2012-05-16, 公開日: 2012-10-10, 最終更新日: 2024-10-30)

主引用文献

Liu, J.,Zhang, S.,Tan, S.,Yi, Y.,Wu, B.,Cao, B.,Zhu, F.,Wang, C.,Wang, H.,Qi, J.,Gao, G.F.
Cross-Allele Cytotoxic T Lymphocyte Responses against 2009 Pandemic H1N1 Influenza A Virus among HLA-A24 and HLA-A3 Supertype-Positive Individuals.
J.Virol., 86:13281-13294, 2012

PubMed Abstract: Lack of a universal vaccine against all serotypes of influenza A viruses and recent progress on T cell-related vaccines against influenza A virus illuminate the important role of human leukocyte antigen (HLA)-restricted cytotoxic T lymphocytes (CTLs) in anti-influenza virus immunity. However, the diverse HLA alleles among humans complicate virus-specific cellular immunity research, and elucidation of cross-HLA allele T cell responses to influenza virus specificity requires further detailed work. An ideal CTL epitope-based vaccine would cover a broad spectrum of epitope antigens presented by most, if not all, of the HLAs. Here, we evaluated the 2009 pandemic influenza A (H1N1) virus-specific T cell responses among the HLA-A24(+) population using a rationally designed peptide pool during the 2009 pandemic. Unexpectedly, cross-HLA allele T cell responses against the influenza A virus peptides were detected among both HLA-A11(+) and HLA-A24(+) donors. Furthermore, we found cross-responses in the entire HLA-A3 supertype population (including HLA-A11, -A31, -A33, and -A30). The cross-allele antigenic peptides within the peptide pool were identified and characterized, and the crystal structures of the major histocompatibility complex (MHC)-peptide complexes were determined. The subsequent HLA-A24-defined cross-allele peptides recognized by the HLA-A11(+) population were shown to mildly bind to the HLA-A*1101 molecule. Together with the structural models, these results partially explain the cross-allele responses. Our findings elucidate the promiscuity of the cross-allele T cell responses against influenza A viruses and are beneficial for the development of a T cell epitope-based vaccine applied in a broader population.

PubMed: 23015716
DOI: 10.1128/JVI.01841-12

実験手法

X-RAY DIFFRACTION (1.7 Å)