Isolation of a human anti-HIV gp41 membrane proximal region neutralizing antibody by antigen-specific single B cell sorting

PLoS One. 2011;6(9):e23532. doi: 10.1371/journal.pone.0023532. Epub 2011 Sep 30.


Broadly neutralizing antibodies are not commonly produced in HIV-1 infected individuals nor by experimental HIV-1 vaccines. When these antibodies do occur, it is important to be able to isolate and characterize them to provide clues for vaccine design. CAP206 is a South African subtype C HIV-1-infected individual previously shown to have broadly neutralizing plasma antibodies targeting the envelope gp41 distal membrane proximal external region (MPER). We have now used a fluoresceinated peptide tetramer antigen with specific cell sorting to isolate a human neutralizing monoclonal antibody (mAb) against the HIV-1 envelope gp41 MPER. The isolated recombinant mAb, CAP206-CH12, utilized a portion of the distal MPER (HXB2 amino acid residues, 673-680) and neutralized a subset of HIV-1 pseudoviruses sensitive to CAP206 plasma antibodies. Interestingly, this mAb was polyreactive and used the same germ-line variable heavy (V(H)1-69) and variable kappa light chain (V(K)3-20) gene families as the prototype broadly neutralizing anti-MPER mAb, 4E10 (residues 672-680). These data indicate that there are multiple immunogenic targets in the C-terminus of the MPER of HIV-1 gp41 envelope and suggests that gp41 neutralizing epitopes may interact with a restricted set of naive B cells during HIV-1 infection.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Antibodies, Monoclonal / chemistry
  • Antibodies, Neutralizing / chemistry
  • Cell Separation
  • Epitopes / chemistry
  • Flow Cytometry / methods
  • Fluorescein / chemistry
  • HIV Envelope Protein gp41 / genetics*
  • HIV Infections / blood
  • HIV-1 / genetics
  • Humans
  • Immunoglobulin Variable Region / chemistry
  • Kinetics
  • Peptides / chemistry
  • Protein Structure, Tertiary
  • Surface Plasmon Resonance


  • Antibodies, Monoclonal
  • Antibodies, Neutralizing
  • Epitopes
  • HIV Envelope Protein gp41
  • Immunoglobulin Variable Region
  • Peptides
  • Fluorescein