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A gp41 MPER-specific Llama VHH Requires a Hydrophobic CDR3 for Neutralization but not for Antigen Recognition
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نویسنده
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lutje hulsik d. ,liu y.-y. ,strokappe n.m. ,battella s. ,el khattabi m. ,mccoy l.e. ,sabin c. ,hinz a. ,hock m. ,macheboeuf p. ,bonvin a.m.j.j. ,langedijk j.p.m. ,davis d. ,forsman quigley a. ,aasa-chapman m.m.i. ,seaman m.s. ,ramos a. ,poignard p. ,favier a. ,simorre j.-p. ,weiss r.a. ,verrips c.t. ,weissenhorn w. ,rutten l.
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منبع
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plos pathogens - 2013 - دوره : 9 - شماره : 3
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چکیده
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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. © 2013 lutje hulsik et al.
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آدرس
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unit of virus host cell interactions (uvhci),umi 3265,université joseph fourier-embl-cnrs,grenoble, France, biomolecular imaging (bmi),faculty of science,utrecht university,utrecht,netherlands,tianjin medical university,tianjing, China, biomolecular imaging (bmi),faculty of science,utrecht university,utrecht, Netherlands, biomolecular imaging (bmi),faculty of science,utrecht university,utrecht, Netherlands, biomolecular imaging (bmi),faculty of science,utrecht university,utrecht, Netherlands, mrc/ucl centre for medical molecular virology,division of infection and immunity,university college london,london, United Kingdom, unit of virus host cell interactions (uvhci),umi 3265,université joseph fourier-embl-cnrs,grenoble, France, unit of virus host cell interactions (uvhci),umi 3265,université joseph fourier-embl-cnrs,grenoble,france,institute of biochemistry,goethe-university frankfurt,frankfurt/main, Germany, unit of virus host cell interactions (uvhci),umi 3265,université joseph fourier-embl-cnrs,grenoble, France, unit of virus host cell interactions (uvhci),umi 3265,université joseph fourier-embl-cnrs,grenoble, France, bijvoet center for biomolecular research,faculty of science,utrecht university,utrecht, Netherlands, pepscan therapeutics bv,lelystad,netherlands,crucell holland bv,leiden, Netherlands, department of virology,biomedical primate research centre (bprc),rijswijk, Netherlands, mrc/ucl centre for medical molecular virology,division of infection and immunity,university college london,london, United Kingdom, mrc/ucl centre for medical molecular virology,division of infection and immunity,university college london,london, United Kingdom, division of viral pathogenesis,beth israel deaconess medical center,harvard medical school,boston,ma, United States, department of immunology and microbial science,international aids vaccine initiative neutralizing antibody center,the scripps research institute,la jolla,ca, United States, department of immunology and microbial science,international aids vaccine initiative neutralizing antibody center,the scripps research institute,la jolla,ca,united states,international aids vaccine initiative,new york,ny, United States, cnrs,institut de biologie structurale-jean-pierre ebel,grenoble cedex,france,cea,institut de biologie structurale-jean-pierre ebel,grenoble cedex,france,ujf-grenoble-1,institut de biologie structurale-jean-pierre ebel,grenoble cedex, France, cnrs,institut de biologie structurale-jean-pierre ebel,grenoble cedex,france,cea,institut de biologie structurale-jean-pierre ebel,grenoble cedex,france,ujf-grenoble-1,institut de biologie structurale-jean-pierre ebel,grenoble cedex, France, mrc/ucl centre for medical molecular virology,division of infection and immunity,university college london,london, United Kingdom, biomolecular imaging (bmi),faculty of science,utrecht university,utrecht,netherlands,qvq bv,utrecht, Netherlands, unit of virus host cell interactions (uvhci),umi 3265,université joseph fourier-embl-cnrs,grenoble, France, biomolecular imaging (bmi),faculty of science,utrecht university,utrecht, Netherlands
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Authors
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