Sequence and structural convergence of broad and potent HIV antibodies that mimic CD4 binding

Science. 2011 Sep 16;333(6049):1633-7. doi: 10.1126/science.1207227. Epub 2011 Jul 14.

Abstract

Passive transfer of broadly neutralizing HIV antibodies can prevent infection, which suggests that vaccines that elicit such antibodies would be protective. Thus far, however, few broadly neutralizing HIV antibodies that occur naturally have been characterized. To determine whether these antibodies are part of a larger group of related molecules, we cloned 576 new HIV antibodies from four unrelated individuals. All four individuals produced expanded clones of potent broadly neutralizing CD4-binding-site antibodies that mimic binding to CD4. Despite extensive hypermutation, the new antibodies shared a consensus sequence of 68 immunoglobulin H (IgH) chain amino acids and arise independently from two related IgH genes. Comparison of the crystal structure of one of the antibodies to the broadly neutralizing antibody VRC01 revealed conservation of the contacts to the HIV spike.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Antibodies, Neutralizing / chemistry*
  • Antibodies, Neutralizing / immunology*
  • Antibodies, Neutralizing / metabolism
  • Antibody Affinity
  • Antibody Specificity
  • Binding Sites
  • Binding Sites, Antibody
  • CD4 Antigens / immunology
  • CD4 Antigens / metabolism*
  • Cloning, Molecular
  • Consensus Sequence
  • Crystallography, X-Ray
  • Genes, Immunoglobulin Heavy Chain
  • HIV Antibodies / chemistry*
  • HIV Antibodies / immunology*
  • HIV Antibodies / metabolism
  • HIV Envelope Protein gp120 / chemistry
  • HIV Envelope Protein gp120 / immunology*
  • HIV Envelope Protein gp120 / metabolism
  • HIV Infections / immunology
  • Humans
  • Immunoglobulin Fab Fragments / chemistry
  • Immunoglobulin Heavy Chains / chemistry
  • Immunoglobulin Light Chains / chemistry
  • Molecular Mimicry
  • Molecular Sequence Data
  • Mutation
  • Protein Conformation

Substances

  • Antibodies, Neutralizing
  • CD4 Antigens
  • HIV Antibodies
  • HIV Envelope Protein gp120
  • Immunoglobulin Fab Fragments
  • Immunoglobulin Heavy Chains
  • Immunoglobulin Light Chains

Associated data

  • GENBANK/HE584535
  • GENBANK/HE584536
  • GENBANK/HE584537
  • GENBANK/HE584538
  • GENBANK/HE584539
  • GENBANK/HE584540
  • GENBANK/HE584541
  • GENBANK/HE584542
  • GENBANK/HE584543
  • GENBANK/HE584544
  • GENBANK/HE584545
  • GENBANK/HE584546
  • GENBANK/HE584547
  • GENBANK/HE584548
  • GENBANK/HE584549
  • GENBANK/HE584550
  • GENBANK/HE584551
  • GENBANK/HE584552
  • GENBANK/HE584553
  • GENBANK/HE584554
  • PDB/3RPI