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Article: Cross-reactive human immunodeficiency virus type 1-neutralizing human monoclonal antibody that recognizes a novel conformational epitope on gp41 and lacks reactivity against self-antigens

TitleCross-reactive human immunodeficiency virus type 1-neutralizing human monoclonal antibody that recognizes a novel conformational epitope on gp41 and lacks reactivity against self-antigens
Authors
Issue Date2008
PublisherAmerican Society for Microbiology. The Journal's web site is located at http://jvi.asm.org/
Citation
Journal Of Virology, 2008, v. 82 n. 14, p. 6869-6879 How to Cite?
AbstractBroadly cross-reactive human immunodeficiency virus (HIV)-neutralizing antibodies are infrequently elicited in infected humans. The two best-characterized gp41-specific cross-reactive neutralizing human monoclonal antibodies, 4E10 and 2F5, target linear epitopes in the membrane-proximal external region (MPER) and bind to cardiolipin and several other autoantigens. It has been hypothesized that, because of such reactivity to self-antigens, elicitation of 2F5 and 4E10 and similar antibodies by vaccine immunogens based on the MPER could be affected by tolerance mechanisms. Here, we report the identification and characterization of a novel anti-gp41 monoclonal antibody, designated m44, which neutralized most of the 22 HIV type 1 (HIV-1) primary isolates from different clades tested in assays based on infection of peripheral blood mononuclear cells by replication-competent virus but did not bind to cardiolipin and phosphatidylserine in an enzyme-linked immunosorbent assay and a Biacore assay nor to any protein or DNA autoantigens tested in Luminex assays. m44 bound to membrane-associated HIV-1 envelope glycoproteins (Envs), to recombinant Envs lacking the transmembrane domain and cytoplasmic tail (gp140s), and to gp41 structures containing five-helix bundles and six-helix bundles, but not to N-heptad repeat trimers, suggesting that the C-heptad repeat is involved in m44 binding. In contrast to 2F5, 4E10, and Z13, m44 did not bind to any significant degree to denatured gp140 and linear peptides derived from gp41, suggesting a conformational nature of the epitope. This is the first report of a gp41-specific cross-reactive HIV-1-neutralizing human antibody that does not have detectable reactivity to autoantigens. Its novel conserved conformational epitope on gp41 could be helpful in the design of vaccine immunogens and as a target for therapeutics. Copyright © 2008, American Society for Microbiology. All Rights Reserved.
Persistent Identifierhttp://hdl.handle.net/10722/157524
ISSN
2015 Impact Factor: 4.606
2015 SCImago Journal Rankings: 3.347
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorZhang, MYen_US
dc.contributor.authorVu, BKen_US
dc.contributor.authorChoudhary, Aen_US
dc.contributor.authorLu, Hen_US
dc.contributor.authorHumbert, Men_US
dc.contributor.authorOng, Hen_US
dc.contributor.authorAlam, Men_US
dc.contributor.authorRuprecht, RMen_US
dc.contributor.authorQuinnan, Gen_US
dc.contributor.authorJiang, Sen_US
dc.contributor.authorMontefiori, DCen_US
dc.contributor.authorMascola, JRen_US
dc.contributor.authorBroder, CCen_US
dc.contributor.authorHaynes, BFen_US
dc.contributor.authorDimitrov, DSen_US
dc.date.accessioned2012-08-08T08:50:55Z-
dc.date.available2012-08-08T08:50:55Z-
dc.date.issued2008en_US
dc.identifier.citationJournal Of Virology, 2008, v. 82 n. 14, p. 6869-6879en_US
dc.identifier.issn0022-538Xen_US
dc.identifier.urihttp://hdl.handle.net/10722/157524-
dc.description.abstractBroadly cross-reactive human immunodeficiency virus (HIV)-neutralizing antibodies are infrequently elicited in infected humans. The two best-characterized gp41-specific cross-reactive neutralizing human monoclonal antibodies, 4E10 and 2F5, target linear epitopes in the membrane-proximal external region (MPER) and bind to cardiolipin and several other autoantigens. It has been hypothesized that, because of such reactivity to self-antigens, elicitation of 2F5 and 4E10 and similar antibodies by vaccine immunogens based on the MPER could be affected by tolerance mechanisms. Here, we report the identification and characterization of a novel anti-gp41 monoclonal antibody, designated m44, which neutralized most of the 22 HIV type 1 (HIV-1) primary isolates from different clades tested in assays based on infection of peripheral blood mononuclear cells by replication-competent virus but did not bind to cardiolipin and phosphatidylserine in an enzyme-linked immunosorbent assay and a Biacore assay nor to any protein or DNA autoantigens tested in Luminex assays. m44 bound to membrane-associated HIV-1 envelope glycoproteins (Envs), to recombinant Envs lacking the transmembrane domain and cytoplasmic tail (gp140s), and to gp41 structures containing five-helix bundles and six-helix bundles, but not to N-heptad repeat trimers, suggesting that the C-heptad repeat is involved in m44 binding. In contrast to 2F5, 4E10, and Z13, m44 did not bind to any significant degree to denatured gp140 and linear peptides derived from gp41, suggesting a conformational nature of the epitope. This is the first report of a gp41-specific cross-reactive HIV-1-neutralizing human antibody that does not have detectable reactivity to autoantigens. Its novel conserved conformational epitope on gp41 could be helpful in the design of vaccine immunogens and as a target for therapeutics. Copyright © 2008, American Society for Microbiology. All Rights Reserved.en_US
dc.languageengen_US
dc.publisherAmerican Society for Microbiology. The Journal's web site is located at http://jvi.asm.org/en_US
dc.relation.ispartofJournal of Virologyen_US
dc.subject.meshAntibodies, Monoclonal - Immunologyen_US
dc.subject.meshAntibodies, Viral - Immunologyen_US
dc.subject.meshAutoantigens - Immunologyen_US
dc.subject.meshCardiolipins - Immunology - Metabolismen_US
dc.subject.meshCell Lineen_US
dc.subject.meshCells, Cultureden_US
dc.subject.meshCross Reactionsen_US
dc.subject.meshDna - Metabolismen_US
dc.subject.meshEnzyme-Linked Immunosorbent Assayen_US
dc.subject.meshEpitopes - Immunologyen_US
dc.subject.meshHiv Envelope Protein Gp41 - Immunologyen_US
dc.subject.meshHiv-1 - Immunologyen_US
dc.subject.meshHumansen_US
dc.subject.meshLeukocytes, Mononuclear - Virologyen_US
dc.subject.meshNeutralization Testsen_US
dc.subject.meshPhosphatidylserines - Immunology - Metabolismen_US
dc.subject.meshProtein Bindingen_US
dc.subject.meshSurface Plasmon Resonanceen_US
dc.titleCross-reactive human immunodeficiency virus type 1-neutralizing human monoclonal antibody that recognizes a novel conformational epitope on gp41 and lacks reactivity against self-antigensen_US
dc.typeArticleen_US
dc.identifier.emailZhang, MY:zhangmy@hku.hken_US
dc.identifier.authorityZhang, MY=rp01409en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1128/JVI.00033-08en_US
dc.identifier.pmid18480433-
dc.identifier.scopuseid_2-s2.0-47049130702en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-47049130702&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume82en_US
dc.identifier.issue14en_US
dc.identifier.spage6869en_US
dc.identifier.epage6879en_US
dc.identifier.isiWOS:000257545300009-
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridZhang, MY=35316639300en_US
dc.identifier.scopusauthoridVu, BK=7003942875en_US
dc.identifier.scopusauthoridChoudhary, A=8743351100en_US
dc.identifier.scopusauthoridLu, H=26642892200en_US
dc.identifier.scopusauthoridHumbert, M=14037179100en_US
dc.identifier.scopusauthoridOng, H=8851846900en_US
dc.identifier.scopusauthoridAlam, M=22633902900en_US
dc.identifier.scopusauthoridRuprecht, RM=7005394971en_US
dc.identifier.scopusauthoridQuinnan, G=7006729933en_US
dc.identifier.scopusauthoridJiang, S=7404453146en_US
dc.identifier.scopusauthoridMontefiori, DC=7005651585en_US
dc.identifier.scopusauthoridMascola, JR=7005343486en_US
dc.identifier.scopusauthoridBroder, CC=7004376461en_US
dc.identifier.scopusauthoridHaynes, BF=26430746300en_US
dc.identifier.scopusauthoridDimitrov, DS=7202564539en_US
dc.identifier.citeulike9432883-

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