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 Haigwood, Edelmira Cabezas, Arnold C. Satterthwait, Iñaki Sanz, Dennis R. Burton

Research output: Contribution to journalArticle

183 Citations (Scopus)

Abstract

A large number (33) of human Fab fragments reacting with HIV-1 surface glycoprotein gp120 have been generated by selection from a combinatorial TgG1κ 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
StatePublished - 1993
Externally publishedYes

Fingerprint

Libraries
Antibody Formation
HIV-1
Light
Antigens
Antibodies
Immunoglobulin Fab Fragments
Membrane Glycoproteins
Bacteriophages
Sequence Analysis
Binding Sites
HIV
Serum
Genes

Keywords

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

ASJC Scopus subject areas

  • Virology

Cite this

Barbas, C. F., Collet, T. A., Amberg, W., Roben, P., Binley, J. M., Hoekstra, D., ... 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.

Molecular profile of an antibody response to HIV-1 as probed by combinatorial libraries. / Barbas, Carlos F.; Collet, Thomas A.; Amberg, Willi; Roben, Paul; Binley, James M.; Hoekstra, Denise; Cababa, Doug; Jones, Terri M.; Williamson, R. Anthony; Pilkington, Glenn R.; Haigwood, Nancy; Cabezas, Edelmira; Satterthwait, Arnold C.; Sanz, Iñaki; Burton, Dennis R.

In: Journal of Molecular Biology, Vol. 230, No. 3, 1993, p. 812-823.

Research output: Contribution to journalArticle

Barbas, CF, Collet, TA, Amberg, W, Roben, P, Binley, JM, Hoekstra, D, Cababa, D, Jones, TM, Williamson, RA, Pilkington, GR, Haigwood, N, Cabezas, E, Satterthwait, AC, Sanz, I & Burton, DR 1993, 'Molecular profile of an antibody response to HIV-1 as probed by combinatorial libraries', Journal of Molecular Biology, vol. 230, no. 3, pp. 812-823.
Barbas CF, Collet TA, Amberg W, Roben P, Binley JM, Hoekstra D et al. Molecular profile of an antibody response to HIV-1 as probed by combinatorial libraries. Journal of Molecular Biology. 1993;230(3):812-823.
Barbas, Carlos F. ; Collet, Thomas A. ; Amberg, Willi ; Roben, Paul ; Binley, James M. ; Hoekstra, Denise ; Cababa, Doug ; Jones, Terri M. ; Williamson, R. Anthony ; Pilkington, Glenn R. ; Haigwood, Nancy ; Cabezas, Edelmira ; Satterthwait, Arnold C. ; Sanz, Iñaki ; Burton, Dennis R. / Molecular profile of an antibody response to HIV-1 as probed by combinatorial libraries. In: Journal of Molecular Biology. 1993 ; Vol. 230, No. 3. pp. 812-823.
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