Human Antibodies That Neutralize HIV-1: Identification, Structures, and B Cell Ontogenies

Immunity. 2012 Sep 21;37(3):412-25. doi: 10.1016/j.immuni.2012.08.012.

Abstract

Antibodies that neutralize diverse strains of HIV-1 develop in ∼20% of HIV-1-infected individuals, and isolation and structural characterization of these antibodies are revealing how they recognize the envelope glycoprotein spike. Broadly reactive neutralizing antibodies utilize just a few sites of spike vulnerability and converge on select modes of recognition. These antibodies have unusual features: uncommonly long complementarity-determining loops, extensive somatic mutation, or both. Recent advances in next-generation sequencing of antibody-gene transcripts are providing genetic records of the development of neutralizing antibodies. These records inform an understanding of the naive B cell repertoire, of somatic mutation, and of the resulting antibody features that are critical to effective HIV-1 neutralization; based on these, we propose an ontogeny and structure-based system of antibody classification. The human immune system is capable of developing antibodies that broadly neutralize HIV-1--and an increasingly detailed view is accumulating for how effective immunity against HIV-1 can be generated.

Publication types

  • Research Support, N.I.H., Intramural
  • Review

MeSH terms

  • Antibodies, Monoclonal / chemistry
  • Antibodies, Monoclonal / immunology
  • Antibodies, Neutralizing / immunology*
  • B-Lymphocytes / immunology*
  • HIV Antibodies / immunology*
  • HIV Envelope Protein gp120 / chemistry
  • HIV Envelope Protein gp120 / immunology
  • HIV Infections / immunology*
  • HIV Infections / virology
  • HIV-1 / immunology*
  • Humans
  • Models, Molecular
  • Protein Structure, Tertiary

Substances

  • Antibodies, Monoclonal
  • Antibodies, Neutralizing
  • HIV Antibodies
  • HIV Envelope Protein gp120