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A gp41 MPER-specific llama VHH requires a hydrophobic CDR3 for neutralization but not for antigen recognition

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  • معلومة اضافية
    • Contributors:
      Unit of Virus Host Cell Interactions = Biologie structurale des interactions entre virus et cellule hôte (UVHCI); Université Joseph Fourier - Grenoble 1 (UJF)-European Molecular Biology Laboratory Grenoble (EMBL)-Centre National de la Recherche Scientifique (CNRS); Departments of Applied Physics New Haven; Yale University New Haven; Research Department of Infection and Population Health London; University College of London London (UCL); Independent Department for Medical Psychology and Medical Sociology; Leipzig University / Universität Leipzig; Beth Israel Deaconess Medical Center Boston (BIDMC); Harvard Medical School Boston (HMS); Centre d'Immunologie de Marseille - Luminy (CIML); Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS); Institut de biologie structurale (IBS - UMR 5075); Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes 2016-2019 (UGA 2016-2019 )-Institut de Recherche Interdisciplinaire de Grenoble (IRIG); Direction de Recherche Fondamentale (CEA) (DRF (CEA)); Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)); Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA); ANR-10-LABX-0049,GRAL,Grenoble Alliance for Integrated Structural Cell Biology(2010)
    • بيانات النشر:
      HAL CCSD
      Public Library of Science
    • الموضوع:
      2013
    • Collection:
      Université Grenoble Alpes: HAL
    • نبذة مختصرة :
      International audience ; The membrane proximal external region (MPER) of the HIV-1 glycoprotein gp41 is targeted by the broadly neutralizing antibodies 2F5 and 4E10. To date, no immunization regimen in animals or humans has produced HIV-1 neutralizing MPER-specific antibodies. We immunized llamas with gp41-MPER proteoliposomes and selected a MPER-specific single chain antibody (VHH), 2H10, whose epitope overlaps with that of mAb 2F5. Bi-2H10, a bivalent form of 2H10, which displayed an approximately 20-fold increased affinity compared to the monovalent 2H10, neutralized various sensitive and resistant HIV-1 strains, as well as SHIV strains in TZM-bl cells. X-ray and NMR analyses combined with mutagenesis and modeling revealed that 2H10 recognizes its gp41 epitope in a helical conformation. Notably, tryptophan 100 at the tip of the long CDR3 is not required for gp41 interaction but essential for neutralization. Thus bi-2H10 is an anti-MPER antibody generated by immunization that requires hydrophobic CDR3 determinants in addition to epitope recognition for neutralization similar to the mode of neutralization employed by mAbs 2F5 and 4E10.
    • Relation:
      info:eu-repo/semantics/altIdentifier/pmid/23505368; PUBMED: 23505368; PUBMEDCENTRAL: PMC3591319
    • الرقم المعرف:
      10.1371/journal.ppat.1003202
    • الدخول الالكتروني :
      https://hal.univ-grenoble-alpes.fr/hal-01241201
      https://hal.univ-grenoble-alpes.fr/hal-01241201v1/document
      https://hal.univ-grenoble-alpes.fr/hal-01241201v1/file/journal.ppat.1003202.PDF
      https://doi.org/10.1371/journal.ppat.1003202
    • Rights:
      http://creativecommons.org/licenses/by/ ; info:eu-repo/semantics/OpenAccess
    • الرقم المعرف:
      edsbas.86B4C945