title: Sequence and structural convergence of broad and potent HIV antibodies that mimic CD4 binding.
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.
authors.affiliation: Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA.
authors.forename: Johannes F
authors.initials: JF
authors.lastname: Scheid
authors.forename: Hugo
authors.initials: H
authors.lastname: Mouquet
authors.forename: Beatrix
authors.initials: B
authors.lastname: Ueberheide
authors.forename: Ron
authors.initials: R
authors.lastname: Diskin
authors.forename: Florian
authors.initials: F
authors.lastname: Klein
authors.forename: Thiago Y K
authors.initials: TY
authors.lastname: Oliveira
authors.forename: John
authors.initials: J
authors.lastname: Pietzsch
authors.forename: David
authors.initials: D
authors.lastname: Fenyo
authors.forename: Alexander
authors.initials: A
authors.lastname: Abadir
authors.forename: Klara
authors.initials: K
authors.lastname: Velinzon
authors.forename: Arlene
authors.initials: A
authors.lastname: Hurley
authors.forename: Sunnie
authors.initials: S
authors.lastname: Myung
authors.forename: Farid
authors.initials: F
authors.lastname: Boulad
authors.forename: Pascal
authors.initials: P
authors.lastname: Poignard
authors.forename: Dennis R
authors.initials: DR
authors.lastname: Burton
authors.forename: Florencia
authors.initials: F
authors.lastname: Pereyra
authors.forename: David D
authors.initials: DD
authors.lastname: Ho
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Walker
authors.forename: Michael S
authors.initials: MS
authors.lastname: Seaman
authors.forename: Pamela J
authors.initials: PJ
authors.lastname: Bjorkman
authors.forename: Brian T
authors.initials: BT
authors.lastname: Chait
authors.forename: Michel C
authors.initials: MC
authors.lastname: Nussenzweig
mesh_terms: D000595:Amino Acid Sequence; D057134:Antibodies, Neutralizing / Q000737:chemistry* / Q000276:immunology* / Q000378:metabolism; D000915:Antibody Affinity; D000918:Antibody Specificity; D001665:Binding Sites; D001666:Binding Sites, Antibody; D015704:CD4 Antigens / Q000276:immunology / Q000378:metabolism*; D003001:Cloning, Molecular; D016384:Consensus Sequence; D018360:Crystallography, X-Ray; D050438:Genes, Immunoglobulin Heavy Chain; D015483:HIV Antibodies / Q000737:chemistry* / Q000276:immunology* / Q000378:metabolism; D015699:HIV Envelope Protein gp120 / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D015658:HIV Infections / Q000276:immunology; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000737:chemistry; D007143:Immunoglobulin Heavy Chains / Q000737:chemistry; D007147:Immunoglobulin Light Chains / Q000737:chemistry; D018716:Molecular Mimicry; D008969:Molecular Sequence Data; D009154:Mutation; D011487:Protein Conformation
chemical_list: D057134:Antibodies, Neutralizing; D015704:CD4 Antigens; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D007140:Immunoglobulin Fab Fragments; D007143:Immunoglobulin Heavy Chains; D007147:Immunoglobulin Light Chains