TY  - JOUR
A1  - Hulsik, David Lutje
A1  - Liu, Ying-ying
A1  - Strokappe, Nika M.
A1  - Battella, Simone
A1  - El Khattabi, Mohamed
A1  - McCoy, Laura E.
A1  - Sabin, Charles
A1  - Hinz, Andreas
A1  - Hock, Miriam
A1  - Macheboeuf, Pauline
A1  - Bonvin, Alexandre M. J. J.
A1  - Langedijk, Johannes P. M.
A1  - Davis, David
A1  - Forsman Quigley, Anna
A1  - Aasa-Chapman, Marlén M. I.
A1  - Seaman, Michael S.
A1  - Ramos, Alejandra
A1  - Poignard, Pascal
A1  - Favier, Adrien
A1  - Simorre, Jean-Pierre
A1  - Weiss, Robin A.
A1  - Verrips, C. Theo
A1  - Weissenhorn, Winfried
A1  - Rutten, Lucy
T1  - A gp41 MPER-specific llama VHH requires a hydrophobic CDR3 for neutralization but not for antigen recognition
T2  - PLoS pathogens
N2  - 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.
Y1  - 2013
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/29065
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-290650
SN  - 1553-7374
SN  - 1553-7366
N1  - Copyright: © 2013 Lutje Hulsik et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
VL  - 9
IS  - (3): e1003202
PB  - PLoS
CY  - Lawrence, Kan.
ER  -