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

Academic Article
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Overview

authors

  • Barbas III, Carlos
  • 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, Dennis

publication date

  • April 1993

journal

  • Journal of Molecular Biology  Journal

abstract

  • A large number (33) of human Fab fragments reacting with HIV-1 surface glycoprotein gp120 have been generated by selection from a combinatorial IgG1 kappa 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.

subject areas

  • Amino Acid Sequence
  • Base Sequence
  • DNA
  • Genomic Library
  • HIV Antibodies
  • HIV Envelope Protein gp120
  • HIV-1
  • Humans
  • Immunoglobulin Heavy Chains
  • Immunoglobulin Variable Region
  • Immunoglobulin kappa-Chains
  • Molecular Sequence Data
  • Sequence Homology, Amino Acid
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Research

keywords

  • ANTIBODIES TO HIV
  • ANTIBODY RESPONSE
  • COMBINATORIAL LIBRARIES
  • HUMAN ANTIBODIES
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Identity

International Standard Serial Number (ISSN)

  • 0022-2836

Digital Object Identifier (DOI)

  • 10.1006/jmbi.1993.1203

PubMed ID

  • 8478936
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Additional Document Info

start page

  • 812

end page

  • 823

volume

  • 230

issue

  • 3

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