title: Antibody light-chain-restricted recognition of the site of immune pressure in the RV144 HIV-1 vaccine trial is phylogenetically conserved.
abstract: In HIV-1, the ability to mount antibody responses to conserved, neutralizing epitopes is critical for protection. Here we have studied the light chain usage of human and rhesus macaque antibodies targeted to a dominant region of the HIV-1 envelope second variable (V2) region involving lysine (K) 169, the site of immune pressure in the RV144 vaccine efficacy trial. We found that humans and rhesus macaques used orthologous lambda variable gene segments encoding a glutamic acid-aspartic acid (ED) motif for K169 recognition. Structure determination of an unmutated ancestor antibody demonstrated that the V2 binding site was preconfigured for ED motif-mediated recognition prior to maturation. Thus, light chain usage for recognition of the site of immune pressure in the RV144 trial is highly conserved across species. These data indicate that the HIV-1 K169-recognizing ED motif has persisted over the diversification between rhesus macaques and humans, suggesting an evolutionary advantage of this antibody recognition mode.
authors.affiliation: Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA. Electronic address: kevin.wiehe@dm.duke.edu.
authors.forename: Kevin
authors.initials: K
authors.lastname: Wiehe
authors.affiliation: Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.
authors.forename: David
authors.initials: D
authors.lastname: Easterhoff
authors.affiliation: Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.
authors.forename: Kan
authors.initials: K
authors.lastname: Luo
authors.affiliation: Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.
authors.forename: Nathan I
authors.initials: NI
authors.lastname: Nicely
authors.affiliation: Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.
authors.forename: Todd
authors.initials: T
authors.lastname: Bradley
authors.affiliation: Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.
authors.forename: Frederick H
authors.initials: FH
authors.lastname: Jaeger
authors.affiliation: Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.
authors.forename: S Moses
authors.initials: SM
authors.lastname: Dennison
authors.affiliation: Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.
authors.forename: Ruijun
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.
authors.forename: Krissey E
authors.initials: KE
authors.lastname: Lloyd
authors.affiliation: Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.
authors.forename: Christina
authors.initials: C
authors.lastname: Stolarchuk
authors.affiliation: Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Parks
authors.affiliation: Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.
authors.forename: Laura L
authors.initials: LL
authors.lastname: Sutherland
authors.affiliation: Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.
authors.forename: Richard M
authors.initials: RM
authors.lastname: Scearce
authors.affiliation: National Institute for Communicable Diseases, Johannesburg 2131, SA and the Centre for the AIDS Programme of Research in South Africa (CAPRISA).
authors.forename: Lynn
authors.initials: L
authors.lastname: Morris
authors.affiliation: Department of Tropical Medicine, Mahidol University, Bangkok 10400, Thailand.
authors.forename: Jaranit
authors.initials: J
authors.lastname: Kaewkungwal
authors.affiliation: Armed Forces Research Institute of Medical Sciences (AFRIMS), Bangkok 10400, Thailand.
authors.forename: Sorachai
authors.initials: S
authors.lastname: Nitayaphan
authors.affiliation: Department of Tropical Medicine, Mahidol University, Bangkok 10400, Thailand.
authors.forename: Punnee
authors.initials: P
authors.lastname: Pitisuttithum
authors.affiliation: Department of Disease Control, Ministry of Public Health, Nonthaburi 11000, Thailand.
authors.forename: Supachai
authors.initials: S
authors.lastname: Rerks-Ngarm
authors.affiliation: Sanofi Pasteur, Inc., Swiftwater, PA 18370, USA.
authors.forename: Faruk
authors.initials: F
authors.lastname: Sinangil
authors.affiliation: Global Solutions for Infectious Diseases, South San Francisco, CA 94080, USA.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Phogat
authors.affiliation: US Military Research Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.
authors.forename: Nelson L
authors.initials: NL
authors.lastname: Michael
authors.affiliation: US Military Research Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.
authors.forename: Jerome H
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.
authors.forename: Garnett
authors.initials: G
authors.lastname: Kelsoe
authors.affiliation: Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.
authors.forename: David C
authors.initials: DC
authors.lastname: Montefiori
authors.affiliation: Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.
authors.forename: Georgia D
authors.initials: GD
authors.lastname: Tomaras
authors.affiliation: Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.
authors.forename: Mattia
authors.initials: M
authors.lastname: Bonsignori
authors.affiliation: Beth Israel Deaconess Medical Center, Harvard University School of Medicine, Boston, MA 02215, USA.
authors.forename: Sampa
authors.initials: S
authors.lastname: Santra
authors.affiliation: Department of Microbiology, Boston University, Boston, MA 02118, USA.
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Kepler
authors.affiliation: Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.
authors.forename: S Munir
authors.initials: SM
authors.lastname: Alam
authors.affiliation: Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.
authors.forename: M Anthony
authors.initials: MA
authors.lastname: Moody
authors.affiliation: Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.
authors.forename: Hua-Xin
authors.initials: HX
authors.lastname: Liao
authors.affiliation: Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA. Electronic address: barton.haynes@dm.duke.edu.
authors.forename: Barton F
authors.initials: BF
authors.lastname: Haynes
mesh_terms: D016915:AIDS Vaccines; D000595:Amino Acid Sequence; D000818:Animals; D000914:Antibodies, Viral / Q000378:metabolism*; D000915:Antibody Affinity / Q000235:genetics; D001402:B-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D002986:Clinical Trials as Topic; D017124:Conserved Sequence / Q000235:genetics; D018604:Epitope Mapping; D018985:Epitopes, B-Lymphocyte / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015699:HIV Envelope Protein gp120 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015658:HIV Infections / Q000276:immunology* / Q000517:prevention & control; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007147:Immunoglobulin Light Chains / Q000378:metabolism*; D008253:Macaca mulatta; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D010802:Phylogeny; D011485:Protein Binding / Q000235:genetics; D015202:Protein Engineering
chemical_list: D016915:AIDS Vaccines; D000914:Antibodies, Viral; D018985:Epitopes, B-Lymphocyte; D015699:HIV Envelope Protein gp120; D007147:Immunoglobulin Light Chains; C514793:gp120 protein, Human immunodeficiency virus 1