title: Multidonor analysis reveals structural elements, genetic determinants, and maturation pathway for HIV-1 neutralization by VRC01-class antibodies.
abstract: Antibodies of the VRC01 class neutralize HIV-1, arise in diverse HIV-1-infected donors, and are potential templates for an effective HIV-1 vaccine. However, the stochastic processes that generate repertoires in each individual of >10(12) antibodies make elicitation of specific antibodies uncertain. Here we determine the ontogeny of the VRC01 class by crystallography and next-generation sequencing. Despite antibody-sequence differences exceeding 50%, antibody-gp120 cocrystal structures reveal VRC01-class recognition to be remarkably similar. B cell transcripts indicate that VRC01-class antibodies require few specific genetic elements, suggesting that naive-B cells with VRC01-class features are generated regularly by recombination. Virtually all of these fail to mature, however, with only a few-likely one-ancestor B cell expanding to form a VRC01-class lineage in each donor. Developmental similarities in multiple donors thus reveal the generation of VRC01-class antibodies to be reproducible in principle, thereby providing a framework for attempts to elicit similar antibodies in the general population.
authors.affiliation: Vaccine Research Center, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Tongqing
authors.initials: T
authors.lastname: Zhou
authors.forename: Jiang
authors.initials: J
authors.lastname: Zhu
authors.forename: Xueling
authors.initials: X
authors.lastname: Wu
authors.forename: Stephanie
authors.initials: S
authors.lastname: Moquin
authors.forename: Baoshan
authors.initials: B
authors.lastname: Zhang
authors.forename: Priyamvada
authors.initials: P
authors.lastname: Acharya
authors.forename: Ivelin S
authors.initials: IS
authors.lastname: Georgiev
authors.forename: Han R
authors.initials: HR
authors.lastname: Altae-Tran
authors.forename: Gwo-Yu
authors.initials: GY
authors.lastname: Chuang
authors.forename: M Gordon
authors.initials: MG
authors.lastname: Joyce
authors.forename: Young Do
authors.initials: YD
authors.lastname: Kwon
authors.forename: Nancy S
authors.initials: NS
authors.lastname: Longo
authors.forename: Mark K
authors.initials: MK
authors.lastname: Louder
authors.forename: Timothy
authors.initials: T
authors.lastname: Luongo
authors.forename: Krisha
authors.initials: K
authors.lastname: McKee
authors.forename: Chaim A
authors.initials: CA
authors.lastname: Schramm
authors.forename: Jeff
authors.initials: J
authors.lastname: Skinner
authors.forename: Yongping
authors.initials: Y
authors.lastname: Yang
authors.forename: Zhongjia
authors.initials: Z
authors.lastname: Yang
authors.forename: Zhenhai
authors.initials: Z
authors.lastname: Zhang
authors.forename: Anqi
authors.initials: A
authors.lastname: Zheng
authors.forename: Mattia
authors.initials: M
authors.lastname: Bonsignori
authors.forename: Barton F
authors.initials: BF
authors.lastname: Haynes
authors.forename: Johannes F
authors.initials: JF
authors.lastname: Scheid
authors.forename: Michel C
authors.initials: MC
authors.lastname: Nussenzweig
authors.forename: Melissa
authors.initials: M
authors.lastname: Simek
authors.forename: Dennis R
authors.initials: DR
authors.lastname: Burton
authors.forename: Wayne C
authors.initials: WC
authors.lastname: Koff
authors.forename: James C
authors.initials: JC
authors.lastname: Mullikin
authors.forename: Mark
authors.initials: M
authors.lastname: Connors
authors.forename: Lawrence
authors.initials: L
authors.lastname: Shapiro
authors.forename: Gary J
authors.initials: GJ
authors.lastname: Nabel
authors.forename: John R
authors.initials: JR
authors.lastname: Mascola
authors.forename: Peter D
authors.initials: PD
authors.lastname: Kwong
mesh_terms: D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000235:genetics* / Q000276:immunology*; D057134:Antibodies, Neutralizing / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D001483:Base Sequence; D000080908:Broadly Neutralizing Antibodies; D018360:Crystallography, X-Ray; D015483:HIV Antibodies / Q000235:genetics* / Q000276:immunology*; D015699:HIV Envelope Protein gp120 / Q000737:chemistry / Q000276:immunology; D015658:HIV Infections / Q000276:immunology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007963:Leukocytes, Mononuclear; D008969:Molecular Sequence Data; D017422:Sequence Analysis, DNA
chemical_list: D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D000080908:Broadly Neutralizing Antibodies; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; C578595:VRC01 monoclonal antibody; C514793:gp120 protein, Human immunodeficiency virus 1
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