dc.contributor.author | Lutje Hulsik, David | |
dc.contributor.author | Liu, Ying-ying | |
dc.contributor.author | Strokappe, Nika M. | |
dc.contributor.author | Battella, Simone | |
dc.contributor.author | El Khattabi, Mohamed | |
dc.contributor.author | McCoy, Laura E. | |
dc.contributor.author | Sabin, Charles | |
dc.contributor.author | Hinz, Andreas | |
dc.contributor.author | Hock, Miriam | |
dc.contributor.author | Macheboeuf, Pauline | |
dc.contributor.author | Bonvin, Alexandre M. J. J. | |
dc.contributor.author | Langedijk, Johannes P. M. | |
dc.contributor.author | Davis, David | |
dc.contributor.author | Forsman Quigley, Anna | |
dc.contributor.author | Aasa-Chapman, Marlén M. I. | |
dc.contributor.author | Seaman, Michael S. | |
dc.contributor.author | Ramos, Alejandra | |
dc.contributor.author | Poignard, Pascal | |
dc.contributor.author | Favier, Adrien | |
dc.contributor.author | Simorre, Jean-Pierre | |
dc.contributor.author | Weiss, Robin A. | |
dc.contributor.author | Verrips, C. Theo | |
dc.contributor.author | Weissenhorn, Winfried | |
dc.contributor.author | Rutten, Lucy | |
dc.date.accessioned | 2013-05-07T14:26:53Z | |
dc.date.issued | 2013 | |
dc.identifier.citation | Lutje Hulsik, David, Ying-ying Liu, Nika M. Strokappe, Simone Battella, Mohamed El Khattabi, Laura E. McCoy, Charles Sabin, et al. 2013. A gp41 MPER-specific llama vhh requires a hydrophobic CDR3 for neutralization but not for antigen recognition. PLoS Pathogens 9(3): e1003202. | en_US |
dc.identifier.issn | 1553-7366 | en_US |
dc.identifier.uri | http://nrs.harvard.edu/urn-3:HUL.InstRepos:10611671 | |
dc.description.abstract | 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. | en_US |
dc.language.iso | en_US | en_US |
dc.publisher | Public Library of Science | en_US |
dc.relation.isversionof | doi:10.1371/journal.ppat.1003202 | en_US |
dc.relation.hasversion | http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3591319/pdf/ | en_US |
dash.license | LAA | |
dc.subject | Biology | en_US |
dc.subject | Biophysics | en_US |
dc.subject | Biomacromolecule-Ligand Interactions | en_US |
dc.subject | Macromolecular Assemblies | en_US |
dc.subject | Microbiology | en_US |
dc.subject | Immunity | en_US |
dc.subject | Adaptive Immunity | en_US |
dc.subject | Immunizations | en_US |
dc.subject | Virology | en_US |
dc.subject | Viral Structure | en_US |
dc.subject | Viral Envelope | en_US |
dc.subject | Antivirals | en_US |
dc.subject | Immunodeficiency Viruses | en_US |
dc.subject | Viral Vaccines | en_US |
dc.subject | Microbial Pathogens | en_US |
dc.title | A gp41 MPER-specific Llama VHH Requires a Hydrophobic CDR3 for Neutralization but not for Antigen Recognition | en_US |
dc.type | Journal Article | en_US |
dc.description.version | Version of Record | en_US |
dc.relation.journal | PLoS Pathogens | en_US |
dash.depositing.author | Seaman, Michael S. | |
dc.date.available | 2013-05-07T14:26:53Z | |
dc.identifier.doi | 10.1371/journal.ppat.1003202 | * |
dash.authorsordered | false | |
dash.contributor.affiliated | Seaman, Michael | |