%0 Journal Article
%T A gp41 MPER-specific Llama VHH Requires a Hydrophobic CDR3 for Neutralization but not for Antigen Recognition
%A David Lutje Hulsik equal contributor
%A Ying-ying Liu equal contributor
%A Nika M. Strokappe
%A Simone Battella
%A Mohamed El Khattabi
%A Laura E. McCoy
%A Charles Sabin
%A Andreas Hinz
%A Miriam Hock
%A Pauline Macheboeuf
%A Alexandre M. J. J. Bonvin
%A Johannes P. M. Langedijk
%A David Davis
%A Anna Forsman Quigley
%A Marl¨Śn M. I. Aasa-Chapman
%A Michael S. Seaman
%A Alejandra Ramos
%A Pascal Poignard
%A Adrien Favier
%A Jean-Pierre Simorre
%A Robin A. Weiss
%A C. Theo Verrips
%A Winfried Weissenhorn
%A Lucy Rutten
%J PLOS Pathogens
%D 2013
%I Public Library of Science (PLoS)
%R 10.1371/journal.ppat.1003202
%X 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.
%U http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1003202