Memory B Cell Antibodies to HIV-1 gp140 Cloned from Individuals Infected with Clade A and B Viruses 英文参考文献.docVIP

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Memory B Cell Antibodies to HIV-1 gp140 Cloned from Individuals Infected with Clade A and B Viruses 英文参考文献.doc

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Memory B Cell Antibodies to HIV-1 gp140 Cloned from Individuals Infected with Clade A and B Viruses 英文参考文献

MemoryBCellAntibodiestoHIV-1gp140Clonedfrom IndividualsInfectedwithCladeAandBViruses HugoMouquet1,FlorianKlein1,JohannesF.Scheid1,2,MalteWarncke3,JohnPietzsch1,4,ThiagoY.K. Oliveira1,5,KlaraVelinzon1,MichaelS.Seaman6,MichelC.Nussenzweig1,7* 1Laboratory of Molecular Immunology, The Rockefeller University, New York, New York, United States of America, 2Charite Universitaetsmedizin, Berlin, Germany, 3Universita¨tsklinikum Hamburg-Eppendorf, Hamburg, Germany, 4Department of Biology, Chemistry, Pharmacy, Freie Universita¨t Berlin, Berlin, Germany, 5Medical SchoolofRibeiraoPreto/USP,DepartmentofGenetics,NationalInstituteofScienceandTechnologyforStemCellsandCellTherapyandCenterforCell-BasedTherapy, RibeiraoPreto,Brazil,6BethIsraelDeaconessMedicalCenter,Boston,Maryland,UnitedStatesofAmerica,7HowardHughesMedicalInstitute,TheRockefellerUniversity, NewYorkCity,NewYork,UnitedStatesofAmerica Abstract Understanding the antibody response to HIV-1 in humans that show broad neutralizing serologic activity is acrucial step in trying to reproduce such responses by vaccination. Investigating antibodies with cross clade reactivity is particularly important asthese antibodies maytarget conserved epitopes ontheHIVenvelope gp160 protein. Tothis endwehaveusedaclade BYU-2gp140 trimeric antigen andsingle-cell antibody cloning methods toobtain 189new anti-gp140 antibodies representing 51 independent Bcell clones from the IgG memory Bcells of 3patients infected with HIV-1 clade A or B viruses and exhibiting broad neutralizing serologic activity. Our results support previous findings showing adiverse antibody response toHIVgp140envelope protein, characterized bydifferentially expanded B-cell clones producing highly hypermutated antibodies withheterogenous gp140-specificity andneutralizing activity. Inaddition totheir high-affinity binding tothe HIVspike, the vast majority ofthe newanti-gp140 antibodies are also polyreactive. Although none of the new antibodies are as broad or potent as VR