Anti-gp41 antibodies cloned from HIV-infected patients with broadly neutralizing serologic activity

J Virol. 2010 May;84(10):5032-42. doi: 10.1128/JVI.00154-10. Epub 2010 Mar 10.


Most HIV-infected individuals develop antibodies to the gp120 and gp41 components of the viral spike; however, only a fraction of these individuals mount a broadly neutralizing serum response against HIV. We have cloned anti-HIV antibodies from the memory B-cell compartment of six individuals with variable viral loads and high titers of broadly neutralizing antibodies. Here, we report on the features of the anti-gp41 response in these patients. Competition experiments with previously characterized antibodies targeting defined epitopes on the gp41 ectodomain showed antibodies directed against the "immunodominant region" (cluster I), the carboxy-terminal heptad repeat (cluster II), and the membrane-proximal external region (cluster IV). On the other hand, antibodies directed against the amino-terminal part of the molecule, including the fusion peptide, polar region, and the N-terminal heptad repeat, were not detected. When all patients' data were combined, unique B-cell clones targeting cluster I, II, and IV accounted for 32%, 49%, and 53% of all anti-gp41-reactive B cells, respectively; therefore, no single region was truly immunodominant. Finally, although we found no new neutralizing epitopes or HIV-1-neutralizing activity by any of the gp41 antibodies at concentrations of up to 50 microg/ml, high concentrations of 7 out of 15 anti-cluster I antibodies neutralized tier 2 viruses.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal / genetics
  • Antibodies, Monoclonal / immunology*
  • Antibodies, Neutralizing / genetics
  • Antibodies, Neutralizing / immunology*
  • Epitopes / immunology
  • HIV Antibodies / genetics
  • HIV Antibodies / immunology*
  • HIV Envelope Protein gp41 / immunology*
  • HIV Infections / immunology*
  • HIV Infections / virology
  • Humans
  • Neutralization Tests


  • Antibodies, Monoclonal
  • Antibodies, Neutralizing
  • Epitopes
  • HIV Antibodies
  • HIV Envelope Protein gp41
  • gp41 protein, Human immunodeficiency virus 1