A gp41 MPER-specific Llama VHH Requires a Hydrophobic CDR3 for Neutralization but not for Antigen Recognition
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A gp41 MPER-specific Llama VHH Requires a Hydrophobic CDR3 for Neutralization but not for Antigen Recognition
| Title: | A gp41 MPER-specific Llama VHH Requires a Hydrophobic CDR3 for Neutralization but not for Antigen Recognition |
| Author: |
Lutje Hulsik, David; Liu, Ying-ying; Strokappe, Nika M.; Battella, Simone; El Khattabi, Mohamed; McCoy, Laura E.; Sabin, Charles; Hinz, Andreas; Hock, Miriam; Macheboeuf, Pauline; Bonvin, Alexandre M. J. J.; Langedijk, Johannes P. M.; Davis, David; Forsman Quigley, Anna; Aasa-Chapman, Marlén M. I.; Seaman, Michael S.; Ramos, Alejandra; Poignard, Pascal; Favier, Adrien; Simorre, Jean-Pierre; Weiss, Robin A.; Verrips, C. Theo; Weissenhorn, Winfried; Rutten, Lucy
Note: Order does not necessarily reflect citation order of authors. |
| 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. |
| Full Text & Related Files: |
3591319.pdf (1.011Mb; PDF) 
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| 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. |
| Published Version: | doi:10.1371/journal.ppat.1003202 |
| Other Sources: | http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3591319/pdf/ |
| Terms of Use: | This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA |
| Citable link to this page: | http://nrs.harvard.edu/urn-3:HUL.InstRepos:10611671 |
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