Dissection of the carbohydrate specificity of the broadly neutralizing anti-HIV-1 antibody 2G12

DOI Web Site 被引用文献5件
  • Daniel A. Calarese
    Departments of Molecular Biology, Chemistry, and Immunology and Molecular Biology and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037; and Institute for Applied Microbiology, University of Natural Resources and Applied Life Sciences, Muthgasse 18, 1190 Vienna, Austria
  • Hing-Ken Lee
    Departments of Molecular Biology, Chemistry, and Immunology and Molecular Biology and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037; and Institute for Applied Microbiology, University of Natural Resources and Applied Life Sciences, Muthgasse 18, 1190 Vienna, Austria
  • Cheng-Yuan Huang
    Departments of Molecular Biology, Chemistry, and Immunology and Molecular Biology and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037; and Institute for Applied Microbiology, University of Natural Resources and Applied Life Sciences, Muthgasse 18, 1190 Vienna, Austria
  • Michael D. Best
    Departments of Molecular Biology, Chemistry, and Immunology and Molecular Biology and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037; and Institute for Applied Microbiology, University of Natural Resources and Applied Life Sciences, Muthgasse 18, 1190 Vienna, Austria
  • Rena D. Astronomo
    Departments of Molecular Biology, Chemistry, and Immunology and Molecular Biology and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037; and Institute for Applied Microbiology, University of Natural Resources and Applied Life Sciences, Muthgasse 18, 1190 Vienna, Austria
  • Robyn L. Stanfield
    Departments of Molecular Biology, Chemistry, and Immunology and Molecular Biology and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037; and Institute for Applied Microbiology, University of Natural Resources and Applied Life Sciences, Muthgasse 18, 1190 Vienna, Austria
  • Hermann Katinger
    Departments of Molecular Biology, Chemistry, and Immunology and Molecular Biology and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037; and Institute for Applied Microbiology, University of Natural Resources and Applied Life Sciences, Muthgasse 18, 1190 Vienna, Austria
  • Dennis R. Burton
    Departments of Molecular Biology, Chemistry, and Immunology and Molecular Biology and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037; and Institute for Applied Microbiology, University of Natural Resources and Applied Life Sciences, Muthgasse 18, 1190 Vienna, Austria
  • Chi-Huey Wong
    Departments of Molecular Biology, Chemistry, and Immunology and Molecular Biology and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037; and Institute for Applied Microbiology, University of Natural Resources and Applied Life Sciences, Muthgasse 18, 1190 Vienna, Austria
  • Ian A. Wilson
    Departments of Molecular Biology, Chemistry, and Immunology and Molecular Biology and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037; and Institute for Applied Microbiology, University of Natural Resources and Applied Life Sciences, Muthgasse 18, 1190 Vienna, Austria

書誌事項

公開日
2005-09-07
DOI
  • 10.1073/pnas.0505763102
公開者
Proceedings of the National Academy of Sciences

この論文をさがす

説明

<jats:p>Human antibody 2G12 neutralizes a broad range of HIV-1 isolates. Hence, molecular characterization of its epitope, which corresponds to a conserved cluster of oligomannoses on the viral envelope glycoprotein gp120, is a high priority in HIV vaccine design. A prior crystal structure of 2G12 in complex with Man<jats:sub>9</jats:sub>GlcNAc<jats:sub>2</jats:sub>highlighted the central importance of the D1 arm in antibody binding. To characterize the specificity of 2G12 more precisely, we performed solution-phase ELISA, carbohydrate microarray analysis, and cocrystallized Fab 2G12 with four different oligomannose derivatives (Man<jats:sub>4</jats:sub>, Man<jats:sub>5</jats:sub>, Man<jats:sub>7</jats:sub>, and Man<jats:sub>8</jats:sub>) that compete with gp120 for binding to 2G12. Our combined studies reveal that 2G12 is capable of binding both the D1 and D3 arms of the Man<jats:sub>9</jats:sub>GlcNAc<jats:sub>2</jats:sub>moiety, which would provide more flexibility to make the required multivalent interactions between the antibody and the gp120 oligomannose cluster than thought previously. These results have important consequences for the design of immunogens to elicit 2G12-like neutralizing antibodies as a component of an HIV vaccine.</jats:p>

収録刊行物

被引用文献 (5)*注記

もっと見る

詳細情報 詳細情報について

問題の指摘

ページトップへ