دورية أكاديمية
A gp41 MPER-specific llama VHH requires a hydrophobic CDR3 for neutralization but not for antigen recognition.
| العنوان: | A gp41 MPER-specific llama VHH requires a hydrophobic CDR3 for neutralization but not for antigen recognition. |
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| المؤلفون: | David Lutje Hulsik, Ying-ying Liu, Nika M Strokappe, Simone Battella, Mohamed El Khattabi, Laura E McCoy, Charles Sabin, Andreas Hinz, Miriam Hock, Pauline Macheboeuf, Alexandre M J J Bonvin, Johannes P M Langedijk, David Davis, Anna Forsman Quigley, Marlén M I Aasa-Chapman, Michael S Seaman, Alejandra Ramos, Pascal Poignard, Adrien Favier, Jean-Pierre Simorre, Robin A Weiss, C Theo Verrips, Winfried Weissenhorn, Lucy Rutten |
| المصدر: | PLoS Pathogens, Vol 9, Iss 3, p e1003202 (2013) |
| بيانات النشر: | Public Library of Science (PLoS), 2013. |
| سنة النشر: | 2013 |
| المجموعة: | LCC:Immunologic diseases. Allergy LCC:Biology (General) |
| مصطلحات موضوعية: | Immunologic diseases. Allergy, RC581-607, Biology (General), QH301-705.5 |
| الوصف: | 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. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1553-7366 1553-7374 |
| Relation: | http://europepmc.org/articles/PMC3591319?pdf=render; https://doaj.org/toc/1553-7366; https://doaj.org/toc/1553-7374 |
| DOI: | 10.1371/journal.ppat.1003202 |
| URL الوصول: | https://doaj.org/article/bedacc53dae644739bdc70b2ea981c66 |
| رقم الأكسشن: | edsdoj.bedacc53dae644739bdc70b2ea981c66 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 15537366 15537374 |
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| DOI: | 10.1371/journal.ppat.1003202 |