Molecular profile of an antibody response to HIV-1 as probed by combinatorial libraries

Carlos F. Barbas, Thomas A. Collet, Willi Amberg, Paul Roben, James M. Binley, Denise Hoekstra, Doug Cababa, Terri M. Jones, R. Anthony Williamson, Glenn R. Pilkington, Nancy L. Haigwood, Edelmira Cabezas, Arnold C. Satterthwait, Iñaki Sanz, Dennis R. Burton

    Research output: Contribution to journalArticle

    185 Scopus citations

    Abstract

    A large number (33) of human Fab fragments reacting with HIV-1 surface glycoprotein gp120 have been generated by selection from a combinatorial TgG1k library displayed on the surface of phage. The library was prepared from a long term asymptomatic HIV-seropositive donor. Analysis of the sequences from these Fabs shows the heavy chains can be placed in groups, many of which contain intraclonal variants, almost certainly corresponding to chains used in vivo. Further variants can be accessed via chain shuffling experiments in which a given light chain is recombined with a library of heavy chains. Heavy chain promiscuity, i.e. the ability of heavy chains to pair with different light chains with retention of antigen binding, is dependent on the particular heavy chain considered and probably excludes the identification of in vivo light chain partners. The antibodies examined here are primarily to the CD4 binding site on gp120 and broadly reflect the serum profile of the donor. The antibodies show evidence of extensive somatic modification indicative of an antigen-driven response. The heavy chain CDR3 regions of the antibodies show a remarkably conserved extended length. A number also show strong sequence conservation in CDR3 against a background of considerable diversity in the rest of the VH gene supporting a central role for this region in antigen recognition.

    Original languageEnglish (US)
    Pages (from-to)812-823
    Number of pages12
    JournalJournal of molecular biology
    Volume230
    Issue number3
    DOIs
    StatePublished - Apr 5 1993

    Keywords

    • Antibodies to HIV
    • Antibody response
    • Combinatorial libraries
    • Human antibodies

    ASJC Scopus subject areas

    • Structural Biology
    • Molecular Biology

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  • Cite this

    Barbas, C. F., Collet, T. A., Amberg, W., Roben, P., Binley, J. M., Hoekstra, D., Cababa, D., Jones, T. M., Williamson, R. A., Pilkington, G. R., Haigwood, N. L., Cabezas, E., Satterthwait, A. C., Sanz, I., & Burton, D. R. (1993). Molecular profile of an antibody response to HIV-1 as probed by combinatorial libraries. Journal of molecular biology, 230(3), 812-823. https://doi.org/10.1006/jmbi.1993.1203