We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
A gp41 MPER-specific Llama VHH Requires a Hydrophobic CDR3 for Neutralization but not for Antigen Recognition.
- Authors
Hulsik, David Lutje; Liu, Ying-ying; Strokappe, Nika M.; Battella, Simone; Khattabi, Mohamed El; McCoy, Laura E.; Sabin, Charles; Hinz, Andreas; Hock, Miriam; Macheboeuf, Pauline; Bonvin, Alexandre M. J. J.; Langedijk, Johannes P. M.; Davis, David; Quigley, Anna Forsman; Aasa-Chapman, Marlén M. I.; Seaman, Michael S.; Ramos, Alejandra; Poignard, Pascal; Favier, Adrien; Simorre, Jean-Pierre
- 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 MPERspecific 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.
- Subjects
GLYCOPROTEINS; LLAMAS; IMMUNOGLOBULINS; EPITOPES; MUTAGENESIS; TRYPTOPHAN
- Publication
PLoS Pathogens, 2013, Vol 9, Issue 3, p1
- ISSN
1553-7366
- Publication type
Article
- DOI
10.1371/journal.ppat.1003202