Structural Survey of Broadly Neutralizing Antibodies Targeting the HIV-1 Env Trimer Delineates Epitope Categories and Characteristics of Recognition

Structure. 2019 Jan 2;27(1):196-206.e6. doi: 10.1016/j.str.2018.10.007. Epub 2018 Nov 21.


Over the past decade, structures have been determined for broadly neutralizing antibodies that recognize all major exposed surfaces of the prefusion-closed HIV-1-envelope (Env) trimer. To understand this recognition and its implications, we analyzed 206 antibody-HIV-1 Env structures from the Protein Data Bank with resolution suitable to define interaction chemistries and measured antibody neutralization on a 208-strain panel. Those with >25% breadth segregated into almost two dozen classes based on ontogeny and recognition and into six epitope categories based on recognized Env residues. For paratope, the number of protruding loops and level of somatic hypermutation were significantly higher for broad HIV-1 neutralizing antibodies than for a comparison set of non-HIV-1 antibodies (p < 0.0001). For epitope, the number of independent sequence segments was higher (p < 0.0001), as well as the glycan component surface area (p = 0.0005). The unusual characteristics of epitope and paratope delineated here are likely to reflect respectively virus-immune evasion and antibody-recognition solutions that allow effective neutralization of HIV-1.

Keywords: B cell ontogeny; X-ray crystallography; antibody recognition; broadly neutralizing antibody; cryo-electron microscopy; envelope glycoprotein trimer; glycan shielding; sequence variation; vaccine design.

Publication types

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

MeSH terms

  • Antibodies, Neutralizing / chemistry*
  • Antibodies, Neutralizing / classification
  • Antibodies, Neutralizing / immunology
  • Antibodies, Viral / chemistry*
  • Antibodies, Viral / classification
  • Antibodies, Viral / immunology
  • Epitopes / chemistry
  • Epitopes / immunology
  • Protein Multimerization
  • env Gene Products, Human Immunodeficiency Virus / chemistry
  • env Gene Products, Human Immunodeficiency Virus / immunology*


  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Epitopes
  • env Gene Products, Human Immunodeficiency Virus