title: Human antibodies that neutralize HIV-1: identification, structures, and B cell ontogenies.
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.
authors.affiliation: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. pdkwong@nih.gov
authors.forename: Peter D
authors.initials: PD
authors.lastname: Kwong
authors.forename: John R
authors.initials: JR
authors.lastname: Mascola
mesh_terms: D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000276:immunology; D057134:Antibodies, Neutralizing / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D015483:HIV Antibodies / Q000276:immunology*; D015699:HIV Envelope Protein gp120 / Q000737:chemistry / Q000276:immunology; D015658:HIV Infections / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D008958:Models, Molecular; D017434:Protein Structure, Tertiary
chemical_list: D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120