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Structural Repertoire of HIV-1-Neutralizing Antibodies Targeting the CD4 Supersite in 14 Donors.
Zhou, Tongqing; Lynch, Rebecca M; Chen, Lei; Acharya, Priyamvada; Wu, Xueling; Doria-Rose, Nicole A; Joyce, M Gordon; Lingwood, Daniel; Soto, Cinque; Bailer, Robert T; Ernandes, Michael J; Kong, Rui; Longo, Nancy S; Louder, Mark K; McKee, Krisha; O'Dell, Sijy; Schmidt, Stephen D; Tran, Lillian; Yang, Zhongjia; Druz, Aliaksandr; Luongo, Timothy S; Moquin, Stephanie; Srivatsan, Sanjay; Yang, Yongping; Zhang, Baoshan; Zheng, Anqi; Pancera, Marie; Kirys, Tatsiana; Georgiev, Ivelin S; Gindin, Tatyana; Peng, Hung-Pin; Yang, An-Suei; Mullikin, James C; Gray, Matthew D; Stamatatos, Leonidas; Burton, Dennis R; Koff, Wayne C; Cohen, Myron S; Haynes, Barton F; Casazza, Joseph P; Connors, Mark; Corti, Davide; Lanzavecchia, Antonio; Sattentau, Quentin J; Weiss, Robin A; West, Anthony P; Bjorkman, Pamela J; Scheid, Johannes F; Nussenzweig, Michel C; Shapiro, Lawrence.
Afiliación
  • Zhou T; Vaccine Research Center, National Institute of Allergy and Infectious Diseases and National Institutes of Health, Bethesda, MD 20892, USA.
  • Lynch RM; Vaccine Research Center, National Institute of Allergy and Infectious Diseases and National Institutes of Health, Bethesda, MD 20892, USA.
  • Chen L; Vaccine Research Center, National Institute of Allergy and Infectious Diseases and National Institutes of Health, Bethesda, MD 20892, USA.
  • Acharya P; Vaccine Research Center, National Institute of Allergy and Infectious Diseases and National Institutes of Health, Bethesda, MD 20892, USA.
  • Wu X; Vaccine Research Center, National Institute of Allergy and Infectious Diseases and National Institutes of Health, Bethesda, MD 20892, USA.
  • Doria-Rose NA; Vaccine Research Center, National Institute of Allergy and Infectious Diseases and National Institutes of Health, Bethesda, MD 20892, USA.
  • Joyce MG; Vaccine Research Center, National Institute of Allergy and Infectious Diseases and National Institutes of Health, Bethesda, MD 20892, USA.
  • Lingwood D; Vaccine Research Center, National Institute of Allergy and Infectious Diseases and National Institutes of Health, Bethesda, MD 20892, USA.
  • Soto C; Vaccine Research Center, National Institute of Allergy and Infectious Diseases and National Institutes of Health, Bethesda, MD 20892, USA.
  • Bailer RT; Vaccine Research Center, National Institute of Allergy and Infectious Diseases and National Institutes of Health, Bethesda, MD 20892, USA.
  • Ernandes MJ; Vaccine Research Center, National Institute of Allergy and Infectious Diseases and National Institutes of Health, Bethesda, MD 20892, USA.
  • Kong R; Vaccine Research Center, National Institute of Allergy and Infectious Diseases and National Institutes of Health, Bethesda, MD 20892, USA.
  • Longo NS; Vaccine Research Center, National Institute of Allergy and Infectious Diseases and National Institutes of Health, Bethesda, MD 20892, USA.
  • Louder MK; Vaccine Research Center, National Institute of Allergy and Infectious Diseases and National Institutes of Health, Bethesda, MD 20892, USA.
  • McKee K; Vaccine Research Center, National Institute of Allergy and Infectious Diseases and National Institutes of Health, Bethesda, MD 20892, USA.
  • O'Dell S; Vaccine Research Center, National Institute of Allergy and Infectious Diseases and National Institutes of Health, Bethesda, MD 20892, USA.
  • Schmidt SD; Vaccine Research Center, National Institute of Allergy and Infectious Diseases and National Institutes of Health, Bethesda, MD 20892, USA.
  • Tran L; Vaccine Research Center, National Institute of Allergy and Infectious Diseases and National Institutes of Health, Bethesda, MD 20892, USA.
  • Yang Z; Vaccine Research Center, National Institute of Allergy and Infectious Diseases and National Institutes of Health, Bethesda, MD 20892, USA.
  • Druz A; Vaccine Research Center, National Institute of Allergy and Infectious Diseases and National Institutes of Health, Bethesda, MD 20892, USA.
  • Luongo TS; Vaccine Research Center, National Institute of Allergy and Infectious Diseases and National Institutes of Health, Bethesda, MD 20892, USA.
  • Moquin S; Vaccine Research Center, National Institute of Allergy and Infectious Diseases and National Institutes of Health, Bethesda, MD 20892, USA.
  • Srivatsan S; Vaccine Research Center, National Institute of Allergy and Infectious Diseases and National Institutes of Health, Bethesda, MD 20892, USA.
  • Yang Y; Vaccine Research Center, National Institute of Allergy and Infectious Diseases and National Institutes of Health, Bethesda, MD 20892, USA.
  • Zhang B; Vaccine Research Center, National Institute of Allergy and Infectious Diseases and National Institutes of Health, Bethesda, MD 20892, USA.
  • Zheng A; Vaccine Research Center, National Institute of Allergy and Infectious Diseases and National Institutes of Health, Bethesda, MD 20892, USA.
  • Pancera M; Vaccine Research Center, National Institute of Allergy and Infectious Diseases and National Institutes of Health, Bethesda, MD 20892, USA.
  • Kirys T; Vaccine Research Center, National Institute of Allergy and Infectious Diseases and National Institutes of Health, Bethesda, MD 20892, USA.
  • Georgiev IS; Vaccine Research Center, National Institute of Allergy and Infectious Diseases and National Institutes of Health, Bethesda, MD 20892, USA.
  • Gindin T; Department of Biochemistry & Molecular Biophysics and Department of Systems Biology, Columbia University, New York, NY 10032, USA.
  • Peng HP; Genomics Research Center, Academia Sinica, and Institute of Biomedical Informatics, National Yang-Ming University, Taipei, Taiwan 11221.
  • Yang AS; Genomics Research Center, Academia Sinica, and Institute of Biomedical Informatics, National Yang-Ming University, Taipei, Taiwan 11221.
  • Mullikin JC; NIH Intramural Sequencing Center, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.
  • Gray MD; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
  • Stamatatos L; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
  • Burton DR; Department of Immunology and Microbial Science, International AIDS Vaccine Initiative Neutralizing Antibody Center, Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA; Ragon Institute of Massachusetts General Hospital, Massachusett
  • Koff WC; International AIDS Vaccine Initiative, New York, NY 10038, USA.
  • Cohen MS; Departments of Medicine, Epidemiology, Microbiology, and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
  • Haynes BF; Duke University Human Vaccine Institute, Departments of Medicine, Surgery, Pediatrics, and Immunology, Duke University School of Medicine and the Center for HIV/AIDS Vaccine Immunology-Immunogen Discovery at Duke University, Durham, NC 27710, USA.
  • Casazza JP; Vaccine Research Center, National Institute of Allergy and Infectious Diseases and National Institutes of Health, Bethesda, MD 20892, USA.
  • Connors M; HIV-Specific Immunity Section, Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases and National Institutes of Health, Bethesda, MD 20892, USA.
  • Corti D; Humabs BioMed SA, Via Mirasole 1, 6500 Bellinzona, Switzerland; Institute for Research in Biomedicine, Università della Svizzera Italiana, Via Vincenzo Vela 6, 6500 Bellinzona, Switzerland.
  • Lanzavecchia A; Institute for Research in Biomedicine, Università della Svizzera Italiana, Via Vincenzo Vela 6, 6500 Bellinzona, Switzerland.
  • Sattentau QJ; Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RF, UK.
  • Weiss RA; Division of Infection & Immunity, University College London, Gower Street, London WC1E 6BT, UK.
  • West AP; Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
  • Bjorkman PJ; Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA; Howard Hughes Medical Institute, California Institute of Technology, Pasadena, CA 91125, USA.
  • Scheid JF; Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA.
  • Nussenzweig MC; Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA; Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10065, USA.
  • Shapiro L; Vaccine Research Center, National Institute of Allergy and Infectious Diseases and National Institutes of Health, Bethesda, MD 20892, USA; Department of Biochemistry & Molecular Biophysics and Department of Systems Biology, Columbia University, New York, NY 10032, USA.
Cell ; 161(6): 1280-92, 2015 Jun 04.
Article en En | MEDLINE | ID: mdl-26004070
ABSTRACT
The site on the HIV-1 gp120 glycoprotein that binds the CD4 receptor is recognized by broadly reactive antibodies, several of which neutralize over 90% of HIV-1 strains. To understand how antibodies achieve such neutralization, we isolated CD4-binding-site (CD4bs) antibodies and analyzed 16 co-crystal structures -8 determined here- of CD4bs antibodies from 14 donors. The 16 antibodies segregated by recognition mode and developmental ontogeny into two types CDR H3-dominated and VH-gene-restricted. Both could achieve greater than 80% neutralization breadth, and both could develop in the same donor. Although paratope chemistries differed, all 16 gp120-CD4bs antibody complexes showed geometric similarity, with antibody-neutralization breadth correlating with antibody-angle of approach relative to the most effective antibody of each type. The repertoire for effective recognition of the CD4 supersite thus comprises antibodies with distinct paratopes arrayed about two optimal geometric orientations, one achieved by CDR H3 ontogenies and the other achieved by VH-gene-restricted ontogenies.
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Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Proteína gp120 de Envoltorio del VIH / VIH-1 / Anticuerpos Neutralizantes / Anticuerpos Antivirales Límite: Humans Idioma: En Revista: Cell Año: 2015 Tipo del documento: Article País de afiliación: Estados Unidos
Texto completo
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PubMed Links
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Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Proteína gp120 de Envoltorio del VIH / VIH-1 / Anticuerpos Neutralizantes / Anticuerpos Antivirales Límite: Humans Idioma: En Revista: Cell Año: 2015 Tipo del documento: Article País de afiliación: Estados Unidos