3MGT

Crystal structure of a H5-specific CTL epitope variant derived from H5N1 influenza virus in complex with HLA-A*0201

3MGT の概要

• エントリーDOI: 10.2210/pdb3mgt/pdb
• 関連するPDBエントリー: 3MGO
• 分子名称: HLA class I histocompatibility antigen, A-2 alpha chain, Beta-2-microglobulin, 10-meric peptide from Hemagglutinin, ... (4 entities in total)
• 機能のキーワード: beta strands-alpha helix, ig-like domain, 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: P01892; Secreted: P61769
• タンパク質・核酸の鎖数: 12
• 化学式量合計: 179899.88

構造登録者

Sun, Y.,Liu, J.,Yang, M.,Gao, F.,Zhou, J.,Kitamura, Y. (登録日: 2010-04-07, 公開日: 2010-05-19, 最終更新日: 2024-10-09)

主引用文献

Sun, Y.,Liu, J.,Yang, M.,Gao, F.,Zhou, J.,Kitamura, Y.,Gao, B.,Tien, P.,Shu, Y.,Iwamoto, A.,Chen, Z.,Gao, G.F.
Identification and structural definition of H5-specific CTL epitopes restricted by HLA-A*0201 derived from the H5N1 subtype of influenza A viruses
J.Gen.Virol., 91:919-930, 2010

PubMed Abstract: The haemagglutinin (HA) glycoprotein of influenza A virus is a major antigen that initiates humoral immunity against infection; however, the cellular immune response against HA is poorly understood. Furthermore, HA-derived cytotoxic T-lymphocyte (CTL) epitopes are relatively rare in comparison to other internal gene products. Here, CTL epitopes of the HA serotype H5 protein were screened. By using in silico prediction, in vitro refolding and a T2 cell-binding assay, followed by immunization of HLA-A2.1/K(b) transgenic mice, an HLA-A*0201-restricted decameric epitope, RI-10 (H5 HA205-214, RLYQNPTTYI), was shown to elicit a robust CTL epitope-specific response. In addition, RI-10 and its variant, KI-10 (KLYQNPTTYI), were also demonstrated to be able to induce a higher CTL epitope-specific response than the influenza A virus dominant CTL epitope GL-9 (GILGFVFTL) in peripheral blood mononuclear cells of HLA-A*0201-positive patients who had recovered from H5N1 virus infection. Furthermore, the crystal structures of RI-10-HLA-A*0201 and KI-10-HLA-A*0201 complexes were determined at 2.3 and 2.2 A resolution, respectively, showing typical HLA-A*0201-restricted epitopes. The conformations of RI-10 and KI-10 in the antigen-presenting grooves in crystal structures of the two complexes show significant differences, despite their nearly identical sequences. These results provide implications for the discovery of diagnostic markers and the design of novel influenza vaccines.

PubMed: 19955560
DOI: 10.1099/vir.0.016766-0

実験手法

X-RAY DIFFRACTION (2.197 Å)