Search Antibody Database

Found 8 matching records:

Displaying record number 779

Download this epitope record as JSON.

MAb ID	D61
HXB2 Location	gp160(592-608) DNA(7998..8048)	gp160 Epitope Map
Author Location	gp41(592-608 HXB2)
Research Contact	Patricia Earl and Christopher Broder, NIH
Epitope	`LLGIWGCSGKLICTTAV`	Epitope Alignment
Subtype	B
Ab Type	gp41 cluster I
Neutralizing
Species (Isotype)	mouse
Patient
Immunogen	vaccine
Keywords	antibody binding site, antibody generation, antibody interactions, genital and mucosal immunity, isotype switch

Vaccine Details

Vaccine type	protein
Vaccine component	Env dimers

Notes

Showing 8 of 8 notes.

D61: D61 was used in competition assays with gp41 Abs cloned from B cells from patients with broadly neutralizing sera. Abs that competed with D61 for binding were assigned to be directed to gp41 cluster I. Pietzsch2010 (antibody interactions)
D61: D61 did not compete with the newly defined neutralizing MAb m44 for binding to gp41. Zhang2008
D61: Several IgG MAbs were isotype switched to IgA and tested for their abilities to generate immune complexes with HIV-1 and be excreted from polarized epithelial cells from the basolateral to the apical surface via polymeric Ig receptor (pIgR) binding. Unlike IgA D10, D47, D19, and D25, IgA D61 was not able to excrete HIV. D61 bound weakly to HIV but the produced immune complex failed to associate with pIgR. These results show that some IgA Abs have potential to excrete HIV from mucosal lamina propria thus decreasing the viral burden and access to susceptible cells. Wright2008 (genital and mucosal immunity, isotype switch)
D61: The fusion process was slowed by using a suboptimal temperature (31.5 C) to re-evaluate the potential of Abs targeting fusion intermediates to block HIV entry -- preincubation of E/T cells at 31.5 C enabled polyclonal anti-N-HR Ab and anti-six-helix bundle Abs to inhibit fusion, indicating six-helix bundles form prior to fusion -- the preincubation 31.5 C step did not alter the inhibitory activity of neutralizing Abs anti-gp41 2F5, or anti-gp120 2G12, IG1b12, 48d, and 17b -- nor did it alter two gp41 MAbs, T9 and D61, inability to inhibit fusion. Database note: First author "GoldingH" is distinct from another author found as both "GoldingB" & "Golding" on annotated papers in this database. GoldingH2002 (antibody binding site)
D61: Binding maps to region 597-613: WGCSGKLICTTAVPWNA -- immunodominant region containing two Cys residues -- this antibody, along with human MAb 246-D, can be blocked by any of a group of 8 conformational MAbs (M10, D41, D54, T4, T6, T9, T10 and T35) -- members of this competition group are blocked by sera from HIV-1+ individuals. Earl1997 (antibody binding site)
D61: Does not precipitate gp41(21-166), but due to a structural difference in the disulfide bonding region near the two cysteines -- the authors propose that this region may change conformation during the activation of the membrane fusion state of the HIV-1 glycoprotein. Weissenhorn1996 (antibody binding site)
D61: Linear gp41 epitope in the cluster I region -- human sera blocked binding in oligomeric ELISA assay to a similar extent for gp41 MAbs D20, D43, D61, and T4. Richardson1996 (antibody binding site)
D61: Generated during a study of the influence of the oligomeric structure of Env in determining the repertoire of the Ab response. Earl1994 (antibody generation)

References

Showing 8 of 8 references.

Isolation Paper
Earl1994 P. L. Earl, C. C. Broder, D. Long, S. A. Lee, J. Peterson, S. Chakrabarti, R. W. Doms, and B. Moss. Native oligomeric human immunodeficiency virus type 1 Envelope glycoprotein elicits diverse monoclonal antibody reactivities. J. Virol., 68:3015-3026, 1994. In a study of the repertoire of response to oligomeric versus monomeric Env protein, 138 murine MAbs were generated in response to an immunogen that was a gp120/bp41 oligomeric molecule that was not cleaved due to a mutation in the cleavage site. The oligomeric molecule was found to elicit a response that was very different than the monomer. Most MAbs were conformational, many were to gp41 or if in gp120, to the CD4 BS. Few MAbs to linear V3 epitopes were produced in response to oligomeric protein, though this was a common specificity in response to immunization with gp120 monomeric protein. PubMed ID: 7512157. Show all entries for this paper.

Earl1997 P. L. Earl, C. C. Broder, R. W. Doms, and B. Moss. Epitope map of human immunodeficiency virus type 1 gp41 derived from 47 monoclonal antibodies produced by immunization with oligomeric envelope protein. J. Virol., 71:2674-84, 1997. PubMed ID: 9060620. Show all entries for this paper.

GoldingH2002 Hana Golding, Marina Zaitseva, Eve de Rosny, Lisa R. King, Jody Manischewitz, Igor Sidorov, Miroslaw K. Gorny, Susan Zolla-Pazner, Dimiter S. Dimitrov, and Carol D. Weiss. Dissection of Human Immunodeficiency Virus Type 1 Entry with Neutralizing Antibodies to gp41 Fusion Intermediates. J. Virol., 76(13):6780-6790, Jul 2002. PubMed ID: 12050391. Show all entries for this paper.

Pietzsch2010 John Pietzsch, Johannes F. Scheid, Hugo Mouquet, Michael S. Seaman, Christopher C. Broder, and Michel C. Nussenzweig. Anti-gp41 Antibodies Cloned from HIV-Infected Patients with Broadly Neutralizing Serologic Activity. J. Virol., 84(10):5032-5042, May 2010. PubMed ID: 20219932. Show all entries for this paper.

Richardson1996 T. M. Richardson, Jr., B. L. Stryjewski, C. C. Broder, J. A. Hoxie, J. R. Mascola, P. L. Earl, and R. W. Doms. Humoral response to oligomeric human immunodeficiency virus type 1 envelope protein. J. Virol., 70:753-62, 1996. An Env antigen capture enzyme-linked immunosorbent assay using a soluble, oligomeric form of HIV-1IIIB Env (gp140) that contains gp120 and the gp41 ectodomain was developed. The gp140, captured by various monoclonal antibodies (MAbs), retained its native oligomeric structure: it bound CD4 and was recognized by MAbs to conformational epitopes in gp120 and gp41, including oligomer-specific epitopes in gp41. PubMed ID: 8551612. Show all entries for this paper.

Weissenhorn1996 W. Weissenhorn, S. A. Wharton, L. J. Calder, P. L. Earl, B. Moss, E. Aliprandis, J. J. Skehel, and D. C. Wiley. The Ectodomain of HIV-1 Env Subunit gp41 Forms a Soluble, alpha-Helical, Rod-Like Oligomer in the Absence of gp120 and the N-Terminal Fusion Peptide. EMBO J., 15:1507-1514, 1996. PubMed ID: 8612573. Show all entries for this paper.

Wright2008 Alison Wright, Michael E. Lamm, and Yung T. Huang. Excretion of Human Immunodeficiency Virus Type 1 through Polarized Epithelium by Immunoglobulin A. J. Virol., 82(23):11526-11535, Dec 2008. PubMed ID: 18829757. Show all entries for this paper.

Zhang2008 Mei-Yun Zhang, Bang K. Vu, Anil Choudhary, Hong Lu, Michael Humbert, Helena Ong, Munir Alam, Ruth M. Ruprecht, Gerald Quinnan, Shibo Jiang, David C. Montefiori, John R. Mascola, Christopher C. Broder, Barton F. Haynes, and Dimiter S. Dimitrov. 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. J. Virol., 82(14):6869-6879, Jul 2008. PubMed ID: 18480433. Show all entries for this paper.

Displaying record number 807

Download this epitope record as JSON.

MAb ID	D50
HXB2 Location	gp160(642-665) DNA(8148..8219)	gp160 Epitope Map
Author Location	gp41(642-665)
Research Contact	Patricia Earl and Christopher Broder, NIH
Epitope	`IHSLIEESQNQQEKNEQELLELDK`	Epitope Alignment
Subtype	B
Ab Type	gp41 cluster II
Neutralizing
Species (Isotype)	mouse
Patient
Immunogen	vaccine
Keywords	antibody binding site, antibody generation, antibody interactions, binding affinity, neutralization, review

Vaccine Details

Vaccine type	protein
Vaccine component	Env dimers

Notes

Showing 16 of 16 notes.

D50: Unlike the MPER MAbs tested, D50 did not show any Env-independent virus capture in the conventional or in the modified version of the virus capture assay. There was an overall reduction in the efficiency of capture of molecular clones (MC) relative to pseudotyped virions by D50. In addition, nontrimeric Envs from JR-CSF MC virus were more efficiently captured by D50 than trimeric JR-FL. Leaman2010
D50: A set of Env variants with deletions in V1/V2 was constructed. Replication competent Env variants with V1/V2 deletions were obtained using virus evolution of V1/V2 deleted variants. Sensitivity of the evolved ΔV1V2 viruses was evaluated to study accessibility of their neutralization epitopes. D50 bound more efficiently to all uncleaved ΔV1V2 variant trimers compared to the full-length trimer, although the differences were minor. Bontjer2010 (binding affinity)
D50: D50 was used in competition assays with gp41 Abs cloned from B cells from patients with broadly neutralizing sera. Abs that competed with D50 for binding were assigned to be directed to gp41 cluster II region. Pietzsch2010 (antibody interactions)
D50: To examine the antigenicity of a defined Ab epitope on the functional envelope spike, a panel of chimeric viruses engrafted at different positions with the hemagglutinin (HA) epitope tag was constructed. D50 neutralized all chimeric viruses poorly, indicating that the quaternary structure of the spikes was maintained. Pantophlet2009 (neutralization)
D50: Stimulation of platelets with gp41 peptides led to a significant reduction of RANTES release which could be restored if platelet cultures with gp41 peptides were performed in the presence of D50. Cognasse2009
D50: D50 did not compete with the newly defined neutralizing MAb m44 for binding to gp41. Zhang2008
D50: D50 was shown to bind to Envs used in typical epitope binding assays, unlike the neutralizing Abs 8K8, DN9, and D5 used in this study. Nelson2008
D50: This review summarizes data on the polyspecific reactivities to host antigens by the broadly neutralizing MAbs IgG1b12, 2G12, 2F5 and 4E10. It also hypothesizes that some broadly reactive Abs might not be routinely made because they are derived from B cell populations that frequently make polyspecific Abs and are thus subjected to B cell negative selection. Different types of anti-MPER Abs are discussed, including D50. Haynes2005a (antibody interactions, review)
D50: This review describes the effectiveness of the current HIV-1 immunogens in eliciting neutralizing antibody responses to different clades of HIV-1. It also summarizes different evasion and antibody escape mechanisms, as well as the most potent neutralizing MAbs and their properties. MAbs reviewed in this article are: 2G12, IgG1b12, 2F5, 4E10, A32, 447-52D and, briefly, D50. Novel immunogen design strategies are also discussed. Haynes2006a (antibody binding site)
D50: The MAb 2F5 binds to the C-heptad and is neutralizing, but the MAb D50 binds to the C-heptad and is not neutralizing. 2F5 binds preferentially to native gp41 prior to receptor activation. D50 prefers the triggered form after receptor activation. Trapped fusion-intermediates suggest 2F5 remains present shortly after gp120 triggering by CD4, but may be lost by the time the six-helix bundle is formed. D50 binds equally to the fusion-intermediate and six-helix bundle. 2F5 neutralization seems to block a later step of the fusion process. deRosny2004 (antibody binding site)
D50: Oligomeric gp140 (o-gp140) derived from R5 primary isolate US4 was characterized for use as a vaccine reagent -- D50 was used to capture the o-gp140 for ELISA to test the antigenecity of o-gp140 using a panel of well characterized MAbs. Srivastava2002
D50: A combination of gp41 fusion with the GNC4 trimeric sequences and disruption of the YU2 gp120-gp41 cleavage site resulted in stable gp140 trimers (gp140-GNC4) -- gp41 MAbs T4, D12, T3, and D50 bound less efficiently to gp140-GNC4 than did pooled sera, but T4 and D12 recognized the gp140-GNC4 timer equivalently to gp140(-), and T3 and D50 recognized the trimer at greater levels than gp140(-). Yang2000 (antibody binding site)
D50: Found to bind to a linear peptide, between Env amino acids 642-655 -- can be blocked by the conformation dependent MAbs D16, D17, D31, D36, D37, D40, D44, D55, D59, T37, and T45 -- the region is in the immunogenic cluster two region -- reactive with 9/10 HIV-1 strains tested, all except HIV-1 ADA, in which the change E659D and E662A may result in the loss of binding (ELLE to DLLA). Earl1997 (antibody binding site)
D50: Richardson suggests this is a linear gp41 epitope. Richardson1996 (antibody binding site)
D50: Thought to be a discontinuous epitope recognizing residues between 649-668 -- designated cluster II -- Fabs D5, D11, G1, T3, M12, M15, S6, S8, S9, S10 block binding. Binley1996 (antibody binding site)
D50: Generated during a study of the influence of the oligomeric structure of Env in determining the repertoire of the Ab response. Earl1994 (antibody generation)

References

Showing 16 of 16 references.

Binley1996 J. M. Binley, H. J. Ditzel, C. F. Barbas III, N. Sullivan, J. Sodroski, P. W. H. I. Parren, and D. R. Burton. Human Antibody Responses to HIV Type 1 Glycoprotein 41 Cloned in Phage Display Libraries Suggest Three Major Epitopes Are Recognized and Give Evidence for Conserved Antibody Motifs in Antigen Binding. AIDS Res. Hum. Retroviruses, 12:911-924, 1996. A panel of anti-gp41 human Fab fragments were generated by panning phage display antibody libraries prepared from HIV-1 positive donors with rgp41. Fabs tended to be directed against three epitopes, designated clusters I-III. None were neutralizing. A common CDR3 motif was found in several of the heavy chain sequences. PubMed ID: 8798976. Show all entries for this paper.

Bontjer2010 Ilja Bontjer, Mark Melchers, Dirk Eggink, Kathryn David, John P. Moore, Ben Berkhout, and Rogier W. Sanders. Stabilized HIV-1 Envelope Glycoprotein Trimers Lacking the V1V2 Domain, Obtained by Virus Evolution. J. Biol. Chem, 285(47):36456-36470, 19 Nov 2010. PubMed ID: 20826824. Show all entries for this paper.

Cognasse2009 Fabrice Cognasse, Hind Hamzeh-Cognasse, Julien Berthet, Pauline Damien, Frédéric Lucht, Bruno Pozzetto, and Olivier Garraud. Altered Release of Regulated upon Activation, Normal T-Cell Expressed and Secreted Protein from Human, Normal Platelets: Contribution of Distinct HIV-1MN gp41 Peptides. AIDS, 23(15):2057-2059, 24 Sep 2009. PubMed ID: 19654498. Show all entries for this paper.

deRosny2004 Eve de Rosny, Russell Vassell, Shibo Jiang, Renate Kunert, and Carol D. Weiss. Binding of the 2F5 Monoclonal Antibody to Native and Fusion-Intermediate Forms of Human Immunodeficiency Virus Type 1 gp41: Implications for Fusion-Inducing Conformational Changes. J. Virol., 78(5):2627-2631, Mar 2004. PubMed ID: 14963170. Show all entries for this paper.

Haynes2005a Barton F. Haynes, M. Anthony Moody, Laurent Verkoczy, Garnett Kelsoe, and S. Munir Alam. Antibody Polyspecificity and Neutralization of HIV-1: A Hypothesis. Hum. Antibodies, 14(3-4):59-67, 2005. PubMed ID: 16720975. Show all entries for this paper.

Haynes2006a Barton F. Haynes and David C. Montefiori. Aiming to Induce Broadly Reactive Neutralizing Antibody Responses with HIV-1 Vaccine Candidates. Expert Rev. Vaccines, 5(4):579-595, Aug 2006. PubMed ID: 16989638. Show all entries for this paper.

Leaman2010 Daniel P. Leaman, Heather Kinkead, and Michael B. Zwick. In-Solution Virus Capture Assay Helps Deconstruct Heterogeneous Antibody Recognition of Human Immunodeficiency Virus Type 1. J. Virol., 84(7):3382-3395, Apr 2010. PubMed ID: 20089658. Show all entries for this paper.

Nelson2008 Josh D. Nelson, Heather Kinkead, Florence M. Brunel, Dan Leaman, Richard Jensen, John M. Louis, Toshiaki Maruyama, Carole A. Bewley, Katherine Bowdish, G. Marius Clore, Philip E. Dawson, Shana Frederickson, Rose G. Mage, Douglas D. Richman, Dennis R. Burton, and Michael B. Zwick. Antibody Elicited against the gp41 N-Heptad Repeat (NHR) Coiled-Coil Can Neutralize HIV-1 with Modest Potency but Non-Neutralizing Antibodies Also Bind to NHR Mimetics. Virology, 377(1):170-183, 20 Jul 2008. PubMed ID: 18499210. Show all entries for this paper.

Pantophlet2009 Ralph Pantophlet, Meng Wang, Rowena O. Aguilar-Sino, and Dennis R. Burton. The Human Immunodeficiency Virus Type 1 Envelope Spike of Primary Viruses Can Suppress Antibody Access to Variable Regions. J. Virol., 83(4):1649-1659, Feb 2009. PubMed ID: 19036813. Show all entries for this paper.

Srivastava2002 Indresh K. Srivastava, Leonidas Stamatatos, Harold Legg, Elaine Kan, Anne Fong, Stephen R. Coates, Louisa Leung, Mark Wininger, John J. Donnelly, Jeffrey B. Ulmer, and Susan W. Barnett. Purification and Characterization of Oligomeric Envelope Glycoprotein from a Primary R5 Subtype B Human Immunodeficiency Virus. J. Virol., 76(6):2835-2847, Mar 2002. URL: http://jvi.asm.org/cgi/content/full/76/6/2835. PubMed ID: 11861851. Show all entries for this paper.

Yang2000 Xinzhen Yang, Michael Farzan, Richard Wyatt, and Joseph Sodroski. Characterization of Stable, Soluble Trimers Containing Complete Ectodomains of Human Immunodeficiency Virus Type 1 Envelope Glycoproteins. J. Virol., 74(12):5716-5725, Jun 2000. PubMed ID: 10823881. Show all entries for this paper.

Displaying record number 613

Download this epitope record as JSON.

MAb ID	D60
HXB2 Location	Env	Env Epitope Map
Author Location	gp120( IIIB)
Research Contact	P. Earl, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD
Epitope
Ab Type	gp120 CD4BS
Neutralizing
Species (Isotype)	mouse(IgG)
Patient
Immunogen	vaccine
Keywords

Vaccine Details

Vaccine type	vaccinia
Vaccine strain	B clade IIIB
Vaccine component	oligomeric gp140

Notes

Showing 2 of 2 notes.

D60: A comparison of 25 gp120 specific, conformation dependent MAbs was done -- D60 is part of a group of MAbs labeled B-I, that had limited cross-reactivity -- of seven clade B isolates BH8 and B-al were they only two that consistently reacted with B-I MAbs -- B-I MAbs fully blocked CD4 binding. Sugiura1999
D60: Generated during a study of the influence of the oligomeric structure of Env in determining the repertoire of the Ab response. Earl1994

References

Showing 3 of 3 references.

Earl1994 P. L. Earl, C. C. Broder, D. Long, S. A. Lee, J. Peterson, S. Chakrabarti, R. W. Doms, and B. Moss. Native oligomeric human immunodeficiency virus type 1 Envelope glycoprotein elicits diverse monoclonal antibody reactivities. J. Virol., 68:3015-3026, 1994. In a study of the repertoire of response to oligomeric versus monomeric Env protein, 138 murine MAbs were generated in response to an immunogen that was a gp120/bp41 oligomeric molecule that was not cleaved due to a mutation in the cleavage site. The oligomeric molecule was found to elicit a response that was very different than the monomer. Most MAbs were conformational, many were to gp41 or if in gp120, to the CD4 BS. Few MAbs to linear V3 epitopes were produced in response to oligomeric protein, though this was a common specificity in response to immunization with gp120 monomeric protein. PubMed ID: 7512157. Show all entries for this paper.

Sugiura1999 W. Sugiura, C. C. Broder, B. Moss, and P. L. Earl. Characterization of conformation-dependent anti-gp120 murine monoclonal antibodies produced by immunization with monomeric and oligomeric human immunodeficiency virus type 1 envelope proteins. Virology, 254:257-67, 1999. PubMed ID: 9986792. Show all entries for this paper.

Displaying record number 864

Download this epitope record as JSON.

MAb ID	T4
HXB2 Location	Env	Env Epitope Map
Author Location	gp41( IIIB)
Epitope
Ab Type
Neutralizing	L
Species (Isotype)	mouse(IgG)
Patient
Immunogen	vaccine
Keywords	antibody binding site, antibody generation, antibody interactions, vaccine antigen design

Vaccine Details

Vaccine type	vaccinia
Vaccine strain	B clade IIIB
Vaccine component	oligomeric gp140

Notes

Showing 9 of 9 notes.

T4: Oligomeric gp140 (o-gp140) derived from R5 primary isolate US4 was characterized for use as a vaccine reagent -- antigen capture ELISA was used to compare the antigenicity of gp120 and o-gp140 using a panel of well characterized MAbs -- T4 recognized o-gp140. Srivastava2002 (antibody binding site)
T4: A combination of gp41 fusion with the GNC4 trimeric sequences and disruption of the YU2 gp120-gp41 cleavage site resulted in stable gp140 trimers (gp140-GNC4) -- gp41 MAbs T4, D12, T3, and D50 bound less efficiently to gp140-GNC4 than did pooled sera, but T4 and D12 recognized the gp140-GNC4 timer equivalently to gp140(-), and T3 and D50 recognized the trimer at greater levels than gp140(-). Yang2000 (vaccine antigen design)
T4: Soluble gp140 derived from SF162, a neutralization-resistant primary isolate, and SF162AV2 a neutralization-susceptible isolate with 30 amino acids deleted from the V2 loop, were generated with or without the gp120-gp41 cleavage site intact -- all forms are recognized by oligomer-specific MAb T4 and show enhanced binding of CD4i MAb 17b when sCD4 is bound -- the fused forms are less efficiently recognized than the cleaved forms by polyclonal neutralizing sera from HIV-infected patients -- the V3 loop is more exposed on the fused form. Stamatatos2000 (vaccine antigen design)
T4: The MAbs with the broadest neutralizing activity, IgG1b12, 2G12 and 2F5, all have high affinity for the native trimer, indicating that they were raised in an immune response to the oligomer on the virion surface rather than dissociated subunits -- a disulfide linked gp120-gp41 (SOS gp140) was created to mimic the native conformation of Env and explore its potential as an immunogen -- SOS gp140 is recognized by NAbs IgG1b12, 2G12, and CD4-IgG2, and also by anti-V3 MAbs 19b and 83.1 -- SOSgp140 is not recognized by C4 region MAbs that neutralize only TCLA strains, G3-42 and G3-519 -- nor did it bind C11, 23A, and M90, MAbs that bind to gp120 C1 and C5, where it interacts with gp41 -- MAbs that bind CD4 inducible epitopes, 17b and A32 were very strongly induced by CD4 in SOS gp140 -- anti-gp41 MAbs that bind in the region that interacts with gp120, 7B2, 2.2B, T4, T15G1 and 4D4, did not bind to SOSgp140, in contrast to 2F5, which binds to the only gp41 epitope that is well exposed in native gp120-gp41 complexes. Binley2000 (vaccine antigen design)
T4: This antibody, along with 7 others (M10, D41, D54, T6, T9, T10 and T35), can block the linear murine MAb D61, and the human MAb 246-D, which both bind to the immunodominant region near the two Cys in gp41 -- most of these antibodies are oligomer dependent -- all of the MAbs are reactive with ten different HIV-1 strains -- members of this competition group are blocked by sera from HIV-1+ individuals. Earl1997 (antibody interactions)
T4: MAbs T4 and T6 bind only to oligomer, and pulse chase experiments indicate that the epitope is very slow to form, requiring one to two hours. Otteken1996 (antibody binding site)
T4: Does not bind to soluble monomeric gp41(21-166) that lacks the fusion peptide and membrane anchor, only to the oligomer gp140, as does T6. Weissenhorn1996 (antibody binding site)
T4: one of five MAbs (T4, T6, T9, T10 and T35) in a competition group that bind to a conformation-dependent epitope in gp41 and is oligomer specific -- neutralizes IIIB and SF2. Broder1994 (antibody binding site)
T4: Generated during a study of the influence of the oligomeric structure of Env in determining the repertoire of the Ab response. Earl1994 (antibody generation)

References

Showing 10 of 10 references.

Broder1994 C.C. Broder, P.L. Earl, D. Long, S.T. Abedon, B. Moss, and R.W. Doms. Antigenic implications of human immunodeficiency virus type 1 envelope quaternary structure: Oligomer-specific and -sensitive monoclonal antibodies. Proc. Natl. Acad. Sci. U.S.A., 91:11699-11703, 1994. 35 anti-gp41 and 27 anti-gp120 murine MAbs generated by immunization with oligomeric HIV-1 IIIB envelope were studied. These MAbs tended to react with conformational epitopes. 21 of the anti-gp41 MAbs reacted preferentially with oligomeric env, while only 1 of the anti-gp120 MAbs reacted more strongly with the oligomer, and 14 of the anti-gp120 preferentially recognized monomeric env. PubMed ID: 7972127. Show all entries for this paper.

Otteken1996 A. Otteken, P. L. Earl, and B. Moss. Folding, assembly, and intracellular trafficking of the human immunodeficiency virus type 1 Envelope glycoprotein analyzed with monoclonal antibodies recognizing maturational intermediates. J. Virol., 70:3407-15, 1996. PubMed ID: 8648672. Show all entries for this paper.

Binley2000 J. Binley, R. Sanders, B. Clas, N. Schuelke, A. Master, Y. Guo, F. Kajumo, D. Anselma, P. Maddon, W. Olson, and J. Moore. A Recombinant Human Immunodeficiency virus type 1 envelope glycoprotein complex stabilized by an intramolecular disulfide bond between the gp120 and gp41 subunits is an antigenic mimic of the trimeric virion associated structure. J. Virol., 74:627-43, 1999. PubMed ID: 10623724. Show all entries for this paper.

Stamatatos2000 L. Stamatatos, M. Lim, and C. Cheng-Mayer. Generation and structural analysis of soluble oligomeric gp140 envelope proteins derived from neutralization-resistant and neutralization-susceptible primary HIV type 1 isolates. AIDS Res. Hum. Retroviruses, 16(10):981--94, 1 Jul 2000. PubMed ID: 10890360. Show all entries for this paper.

Displaying record number 865

Download this epitope record as JSON.

MAb ID	D12
HXB2 Location	Env	Env Epitope Map
Author Location	gp41( IIIB)
Research Contact	Patricia Earl and Christopher Broder, NIH
Epitope
Ab Type
Neutralizing	L
Species (Isotype)	mouse(IgG)
Patient
Immunogen	vaccine
Keywords	antibody binding site, antibody generation, antibody interactions, vaccine antigen design

Vaccine Details

Vaccine type	vaccinia
Vaccine strain	B clade IIIB
Vaccine component	oligomeric gp140

Notes

Showing 7 of 7 notes.

D12: A combination of gp41 fusion with the GNC4 trimeric sequences and disruption of the YU2 gp120-gp41 cleavage site resulted in stable gp140 trimers (gp140-GNC4) -- gp41 MAbs T4, D12, T3, and D50 bound less efficiently to gp140-GNC4 than did pooled sera, but T4 and D12 recognized the gp140-GNC4 timer equivalently to gp140(-), and T3 and D50 recognized the trimer at greater levels than gp140(-). Yang2000 (vaccine antigen design)
D12: D12 was used in WB of HIV-1 transmembrane proteins in a study which showed that determinants of HIV-1 CD4 independence map outside regions required for coreceptor specificity -- IIIBx, a CD4-independent variant of IIIB, has a truncated gp41. LaBranche1999
D12: MAbs D4, D10, D11, D12, and D41 all bind only to complete oligomer -- pulse label experiments of MAb binding to noncleavable gp160 revealed that these MAbs bound with a delay, epitopes forming with a half life of 30 min. Otteken1996 (antibody binding site)
D12: MAbs D10 and D12 are very easily blocked by human sera from HIV+ individuals. Earl1997
D12: This antibody was blocked more strongly by human sera than other anti-gp41 MAbs (D20, D43, D61, and T4) in a oligomeric ELISA assay. Richardson1996 (antibody interactions)
D12: One of 18 MAbs (e. g. D4 and D40) that bind to a conformation-dependent epitope in gp41 that bind preferentially, but not exclusively, to oligomers -- neutralizes IIIB and SF2. Broder1994 (antibody binding site)
D12: Generated during a study of the influence of the oligomeric structure of Env in determining the repertoire of the Ab response. Earl1994 (antibody generation)

References

Showing 7 of 7 references.

LaBranche1999 C. C. LaBranche, T. L. Hoffman, J. Romano, B. S. Haggarty, T. G. Edwards, T. J. Matthews, R. W. Doms, and J. A. Hoxie. Determinants of CD4 independence for a human immunodeficiency virus type 1 variant map outside regions required for coreceptor specificity. J. Virol., 73(12):10310--9, Dec 1999. URL: http://jvi.asm.org/cgi/content/full/73/12/10310. PubMed ID: 10559349. Show all entries for this paper.

Displaying record number 400

Download this epitope record as JSON.

MAb ID	D47
HXB2 Location	Env	Env Epitope Map
Author Location	gp120( IIIB)
Research Contact	Patricia Earl, NIAID, NIH
Epitope
Ab Type	gp120 V3 // V3 glycan (V3g)
Neutralizing
Species (Isotype)	mouse
Patient
Immunogen	vaccine
Keywords	antibody binding site, antibody generation, genital and mucosal immunity, isotype switch, neutralization, variant cross-reactivity

Vaccine Details

Vaccine type	vaccinia
Vaccine strain	B clade IIIB
Vaccine component	Env

Notes

Showing 9 of 9 notes.

D47: D47 did not compete with the newly defined neutralizing MAb m44 for binding to gp41. Zhang2008
D47: Several IgG MAbs were isotype switched to IgA and tested for their abilities to generate immune complexes with HIV-1 and be excreted from polarized epithelial cells from the basolateral to the apical surface via polymeric Ig receptor (pIgR) binding. IgA D47 showed robust excretion abilities which corresponded to increased binding of D47 to HIV, and, as immune complex with the virus, to pIgR. The excretion of the D47-HIV complex was IgA Ab concentration dependent, as well as time dependent, depending on the duration of basolateral exposure of the immune complexes. Immune complexes with D10 plus D47 showed synergistic abilities, as the binding and excretion increased significantly with both Abs present than with only one of the Abs. D47 excreted noninfectious virus, correlating with it being a neutralizing Ab. These results show that IgA Abs have potential to excrete HIV from mucosal lamina propria thus decreasing the viral burden and access to susceptible cells. Wright2008 (genital and mucosal immunity, isotype switch)
D47: By isotype switching, IgG and IgA variants of D47 were produced. Both D47 IgA and IgG neutralized virus in conventional neutralization assays, however, IgA performed better. D47 IgA was also internalized into the cells by the polymeric Ig receptor (pIgR) and showed capability of intracellular neutralization of HIV-1, while D47 IgG showed no such activity. The extent of intracellular neutralization was shown to be dependent on the concentration of D47 IgA. D47 IgA also inhibited production of virus. Huang2005a (genital and mucosal immunity, isotype switch, neutralization)
D47: sCD4 can activate fusion between effector cells expressing Env and target cells expressing coreceptor (CCR5 or CXCR4) alone without CD4 -- V3 MAb D47 is strain specific and can inhibit sCD4 mediated infection, but only of the closely related LAV Env, while anti-CD4i MAbs were broadly cross-neutralizing. Salzwedel2000 (variant cross-reactivity)
D47: Used for comparison in a study of gp41 antibodies -- D47 binds to a greater extent to cell surface expressed Env than any of 38 conformation dependent anti-gp41 MAbs. Earl1997
D47: Binds both gp120 and soluble gp120+gp41 complex efficiently, suggesting its gp120 epitope is not blocked by gp41 binding. Wyatt1997 (antibody binding site)
D47: Pulse label experiments of MAb binding to noncleavable gp160 revealed that this anti-V3 MAb bound immediately and binding stayed constant through chase period. Otteken1996
D47: Used for capture of oligomeric Env for antigen capture ELISA -- binding of this antibody to oligomeric Env IIIB was not blocked by human sera from the US, consistent with a low prevalence of IIIB-like V3 strains. Richardson1996 (antibody binding site)
D47: Generated during a study of the influence of the oligomeric structure of Env in determining the repertoire of the Ab response. Earl1994 (antibody generation)

References

Showing 9 of 9 references.

Wyatt1997 R. Wyatt, E. Desjardin, U. Olshevsky, C. Nixon, J. Binley, V. Olshevsky, and J. Sodroski. Analysis of the Interaction of the Human Immunodeficiency Virus Type 1 gp120 Envelope Glycoprotein with the gp41 Transmembrane Glycoprotein. J. Virol., 71:9722-9731, 1997. This study characterized the binding of gp120 and gp41 by comparing Ab reactivity to soluble gp120 and to a soluble complex of gp120 and gp41 called sgp140. The occlusion of gp120 epitopes in the sgp140 complex provides a guide to the gp120 domains that interact with gp41, localizing them in C1 and C5 of gp120. Mutations that disrupt the binding of the occluded antibodies do not influence NAb binding or CD4 binding, thus if the gp41 binding domain is deleted, the immunologically desirable features of gp120 for vaccine design are still intact. PubMed ID: 9371638. Show all entries for this paper.

Salzwedel2000 K. Salzwedel, E. D. Smith, B. Dey, and E. A. Berger. Sequential CD4-Coreceptor Interactions in Human Immunodeficiency Virus Type 1 Env Function: Soluble CD4 Activates Env for Coreceptor-Dependent Fusion and Reveals Blocking Activities of Antibodies against Cryptic Conserved Epitopes on gp120. J. Virol., 74:326-333, 2000. PubMed ID: 10590121. Show all entries for this paper.

Huang2005a Yung T. Huang, Alison Wright, Xing Gao, Lesya Kulick, Huimin Yan, and Michael E. Lamm. Intraepithelial Cell Neutralization of HIV-1 Replication by IgA. J. Immunol., 174(8):4828-4835, 15 Apr 2005. PubMed ID: 15814709. Show all entries for this paper.

Displaying record number 869

Download this epitope record as JSON.

MAb ID	D43
HXB2 Location	Env	Env Epitope Map
Author Location	gp41( HXB2)
Research Contact	Patricia Earl and Christopher Broder, NIH
Epitope
Subtype	B
Ab Type
Neutralizing
Species (Isotype)	mouse(IgG)
Patient
Immunogen	vaccine
Keywords

Vaccine Details

Vaccine type	protein
Vaccine component	Env dimers

Notes

Showing 3 of 3 notes.

D43: Partially conformation dependent -- doesn't bind to short peptides, but does bind to the region spanning 641-683 -- binding can be blocked by MAbs T3, D38 and D45 -- MAbs in this competition group reacted with 9/10 HIV-1 strains, not binding to JRFL. Earl1997
D43: This is a linear gp41 epitope, mapping in the region 635-678 -- human sera blocked binding in oligomeric ELISA assay to a similar extent for gp41 MAbs D20, D43, D61, and T4. Richardson1996
D43: Generated during a study of the influence of the oligomeric structure of Env in determining the repertoire of the Ab response. Earl1994

References

Showing 3 of 3 references.

Displaying record number 612

Download this epitope record as JSON.

MAb ID	D20
HXB2 Location	Env	Env Epitope Map
Author Location	gp120( IIIB)
Research Contact	P. Earl, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD
Epitope
Ab Type	gp120 CD4BS
Neutralizing
Species (Isotype)	mouse(IgG)
Patient
Immunogen	vaccine
Keywords	antibody binding site, antibody generation

Vaccine Details

Vaccine type	vaccinia
Vaccine strain	B clade IIIB
Vaccine component	oligomeric gp140

Notes

Showing 6 of 6 notes.

D20: A comparison of 25 gp120 specific, conformation dependent MAbs was done -- D20 is part of a group of MAbs labeled A1 -- all A1 MAbs were broadly cross-reactive with gp160 from B-clade R5, X4, and R5X4 viruses, blocked CD4 binding, were sensitive to mutations in gp120 positions 368 and 370 that directly contact CD4. Sugiura1999 (antibody binding site)
D20: Used for comparison in a study of gp41 antibodies -- D20 binds to a greater extent to cell surface expressed Env than any of 38 conformation dependent anti-gp41 MAbs. Earl1997 (antibody binding site)
D20: Pulse label experiments of 4 MAbs (D20, D27, T20, and T22) binding to noncleavable gp160 revealed that these anti-CD4 MAbs bound with a delay, and that the epitope formed with a t 1/2 of about 10 minutes. Otteken1996
D20: Human sera blocked binding in oligomeric ELISA assay to a similar extent for gp41 MAbs D20, D43, D61, and T4. Richardson1996
D20: Binding completely blocked by pooled human sera. Broder1994
D20: Generated during a study of the influence of the oligomeric structure of Env in determining the repertoire of the Ab response. Earl1994 (antibody generation)

References

Showing 6 of 6 references.