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MAb ID 50-69 (SZ-50.69, 50-69D, 50.69, 50-6910)
HXB2 Location Env
DNA(7959..8033)
Env Epitope Map
Author Location gp41( BH10)
Research Contact Susan Zolla-Pazner (Zollas01@mcrcr6.med.nyu), NYU, NY
Epitope (Discontinuous epitope)
Ab Type gp41 cluster I
Neutralizing  
Species (Isotype) human(IgG2κ)
Patient  
Immunogen HIV-1 infection
Keywords ADCC, antibody binding site, antibody generation, antibody interactions, antibody polyreactivity, antibody sequence, binding affinity, complement, dendritic cells, enhancing activity, immunotoxin, kinetics, mimotopes, neutralization, rate of progression, review, subtype comparisons, vaccine antigen design, vaccine-induced immune responses, variant cross-reactivity

Notes

Showing 44 of 44 notes.

References

Showing 44 of 44 references.

Isolation Paper
Gorny1989 M. K. Gorny, V. Gianakakos, S. Sharpe, and S. Zolla-Pazner. Generation of human monoclonal antibodies to human immunodeficiency virus. Proc. Natl. Acad. Sci. U.S.A., 86:1624-1628, 1989. This paper described immortalization of B-cells from HIV-1 positive individuals with Epstein-Barr virus, to produce seven stable antibody producing cell lines. PubMed ID: 2922401. Show all entries for this paper.

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.

Boots1997 L. J. Boots, P. M. McKenna, B. A. Arnold, P. M. Keller, M. K. Gorny, S. Zolla-Pazner, J. E. Robinson, and A. J. Conley. Anti-human immunodeficiency virus type 1 human monoclonal antibodies that bind discontinuous epitopes in the viral glycoproteins can identify mimotopes from recombinant phage peptide display libraries. AIDS Res. Hum. Retroviruses, 13:1549-59, 1997. PubMed ID: 9430247. Show all entries for this paper.

Chen1995 C. H. Chen, T. J. Matthews, C. B. McDanal, D. P. Bolognesi, and M. L. Greenberg. A Molecular Clasp in the Human Immunodeficiency Virus (HIV) Type 1 TM Protein Determines the Anti-HIV Activity of gp41 Derivatives: Implication for Viral Fusion. J. Virol., 69:3771-3777, 1995. PubMed ID: 7538176. Show all entries for this paper.

Dennison2011a S. Moses Dennison, Kara Anasti, Richard M. Scearce, Laura Sutherland, Robert Parks, Shi-Mao Xia, Hua-Xin Liao, Miroslaw K. Gorny, Susan Zolla-Pazner, Barton F. Haynes, and S. Munir Alam. Nonneutralizing HIV-1 gp41 Envelope Cluster II Human Monoclonal Antibodies Show Polyreactivity for Binding to Phospholipids and Protein Autoantigens. J. Virol., 85(3):1340-1347, Feb 2011. PubMed ID: 21106741. Show all entries for this paper.

Eddleston1993 M. Eddleston, J. C. de la Torre, J.-Y. Xu, N. Dorfman, A. Notkins, S. Zolla-Pazner, and M. B. A. Oldstone. Molecular Mimicry Accompanying HIV-1 Infection: Human Monoclonal Antibodies That Bind to gp41 and to Astrocytes. AIDS Res. Hum. Retroviruses, 10:939-944, 1993. In this paper, three anti-HIV-1 gp41 specific MAbs were found to react with astrocytes: 98-6, 167-7 and 15G1. Reactive astrocytes in the hippocampus were most prominently involved, and the antibodies stained no other cell type in the brain, kidney or liver. All three mapped to a conformationally dependent epitope between aa 644-663. PubMed ID: 7506553. Show all entries for this paper.

Finnegan2002 Catherine M. Finnegan, Werner Berg, George K. Lewis, and Anthony L. DeVico. Antigenic Properties of the Human Immunodeficiency Virus Transmembrane Glycoprotein during Cell-Cell Fusion. J. Virol., 76(23):12123-12134, Dec 2002. PubMed ID: 12414953. Show all entries for this paper.

Follis2002 Kathryn E. Follis, Scott J. Larson, Min Lu, and Jack H. Nunberg. Genetic Evidence that Interhelical Packing Interactions in the gp41 Core Are Critical for Transition of the Human Immunodeficiency Virus Type 1 Envelope Glycoprotein to the Fusion-Active State. J. Virol., 76(14):7356-7362, Jul 2002. PubMed ID: 12072535. Show all entries for this paper.

Gorny2000a M. K. Gorny and S. Zolla-Pazner. Recognition by Human Monoclonal Antibodies of Free and Complexed Peptides Representing the Prefusogenic and Fusogenic Forms of Human Immunodeficiency Virus Type 1 gp41. J. Virol., 74:6186-6192, 2000. PubMed ID: 10846104. Show all entries for this paper.

Gorny2000b M. K. Gorny, T. C. VanCott, C. Williams, K. Revesz, and S. Zolla-Pazner. Effects of oligomerization on the epitopes of the human immunodeficiency virus type 1 envelope glycoproteins. Virology, 267:220-8, 2000. PubMed ID: 10662617. Show all entries for this paper.

Gorny2003 Miroslaw K. Gorny and Susan Zolla-Pazner. Human Monoclonal Antibodies that Neutralize HIV-1. In Bette T. M. Korber and et. al., editors, HIV Immunology and HIV/SIV Vaccine Databases 2003. pages 37--51. Los Alamos National Laboratory, Theoretical Biology \& Biophysics, Los Alamos, N.M., 2004. URL: http://www.hiv.lanl.gov/content/immunology/pdf/2003/zolla-pazner_article.pdf. LA-UR 04-8162. Show all entries for this paper.

Gorny2009 Miroslaw K. Gorny, Xiao-Hong Wang, Constance Williams, Barbara Volsky, Kathy Revesz, Bradley Witover, Sherri Burda, Mateusz Urbanski, Phillipe Nyambi, Chavdar Krachmarov, Abraham Pinter, Susan Zolla-Pazner, and Arthur Nadas. Preferential Use of the VH5-51 Gene Segment by the Human Immune Response to Code for Antibodies against the V3 Domain of HIV-1. Mol. Immunol., 46(5):917-926, Feb 2009. PubMed ID: 18952295. Show all entries for this paper.

Hioe1997b C. E. Hioe, S. Xu, P. Chigurupati, S. Burda, C. Williams, M. K. Gorny, and S. Zolla-Pazner. Neutralization of HIV-1 Primary Isolates by Polyclonal and Monoclonal Human Antibodies. Int. Immunol., 9(9):1281-1290, Sep 1997. PubMed ID: 9310831. Show all entries for this paper.

Holl2006 Vincent Holl, Maryse Peressin, Thomas Decoville, Sylvie Schmidt, Susan Zolla-Pazner, Anne-Marie Aubertin, and Christiane Moog. Nonneutralizing Antibodies Are Able To Inhibit Human Immunodeficiency Virus Type 1 Replication in Macrophages and Immature Dendritic Cells. J. Virol., 80(12):6177-6181, Jun 2006. PubMed ID: 16731957. Show all entries for this paper.

Huang2007 Li Huang, Weihong Lai, Phong Ho, and Chin Ho Chen. Induction of a Nonproductive Conformational Change in gp120 by a Small Molecule HIV Type 1 Entry Inhibitor. AIDS Res. Hum. Retroviruses, 23(1):28-32, Jan 2007. PubMed ID: 17263629. Show all entries for this paper.

Kalia2005 Vandana Kalia, Surojit Sarkar, Phalguni Gupta, and Ronald C. Montelaro. Antibody Neutralization Escape Mediated by Point Mutations in the Intracytoplasmic Tail of Human Immunodeficiency Virus Type 1 gp41. J. Virol., 79(4):2097-2107, Feb 2005. PubMed ID: 15681412. Show all entries for this paper.

Kim2007 Mikyung Kim, Zhisong Qiao, Jessica Yu, David Montefiori, and Ellis L. Reinherz. Immunogenicity of Recombinant Human Immunodeficiency Virus Type 1-Like Particles Expressing gp41 Derivatives in a Pre-Fusion State. Vaccine, 25(27):5102-5114, 28 Jun 2007. PubMed ID: 17055621. Show all entries for this paper.

Klasse1996 P. J. Klasse and Q. J. Sattentau. Altered CD4 Interactions of HIV Type 1 LAI Variants Selected for the Capacity to Induce Membrane Fusion in the Presence of a Monoclonal Antibody to Domain 2 of CD4. AIDS Res. Hum. Retroviruses, 12:1015-1021, 1996. PubMed ID: 8827217. Show all entries for this paper.

Laal1994 Suman Laal, Sherri Burda, Miroslav K. Gorny, Sylwia Karwowska, Aby Buchbinder, and Susan Zolla-Pazner. Synergistic Neutralization of Human Immunodeficiency Virus Type 1 by Combinations of Human Monoclonal Antibodies. J. Virol., 68(6):4001-4008, Jun 1994. PubMed ID: 7514683. Show all entries for this paper.

Ling2004 Hong Ling, Peng Xiao, Osamu Usami, and Toshio Hattori. Thrombin Activates Envelope Glycoproteins of HIV Type 1 and Enhances Fusion. Microbes Infect., 6(5):414-420, Apr 2004. PubMed ID: 15109955. Show all entries for this paper.

Manca1995 F. Manca, D. Fenoglio, M. T. Valle, G. L. Pira, A. Kunkl, R. S. Balderas, R. G. Baccala, D. H. Kono, A. Ferraris, D. Saverino, F. Lancia, L. Lozzi, and A. N. Theofilopoulos. Human T helper cells specific for HIV reverse transcriptase: possible role in intrastructural help for HIV envelope-specific antibodies. Eur. J. Immunol., 25:1217-1223, 1995. PubMed ID: 7539750. Show all entries for this paper.

McCaffrey2004 Ruth A McCaffrey, Cheryl Saunders, Mike Hensel, and Leonidas Stamatatos. N-Linked Glycosylation of the V3 Loop and the Immunologically Silent Face of gp120 Protects Human Immunodeficiency Virus Type 1 SF162 from Neutralization by Anti-gp120 and Anti-gp41 Antibodies. J. Virol., 78(7):3279-3295, Apr 2004. PubMed ID: 15016849. Show all entries for this paper.

McDougal1996 J. S. McDougal, M. S. Kennedy, S. L. Orloff, J. K. A. Nicholson, and T. J. Spira. Mechanisms of Human Immunodeficiency Virus Type 1 (HIV-1) Neutralization: Irreversible Inactivation of Infectivity by Anti-HIV-1 Antibody. J. Virol., 70:5236-5245, 1996. Studies of polyclonal sera autologous virus inactivation indicates that in individuals over time, viral populations emerge that are resistant to inactivating effects of earlier sera. PubMed ID: 8764033. Show all entries for this paper.

Mitchell1998 W. M. Mitchell, L. Ding, and J. Gabriel. Inactivation of a Common Epitope Responsible for the Induction of Antibody-Dependent Enhancement of HIV. AIDS, 12:147-156, 1998. PubMed ID: 9468363. Show all entries for this paper.

Nyambi2000 P. N. Nyambi, H. A. Mbah, S. Burda, C. Williams, M. K. Gorny, A. Nadas, and S. Zolla-Pazner. Conserved and Exposed Epitopes on Intact, Native, Primary Human Immunodeficiency Virus Type 1 Virions of Group M. J. Virol., 74:7096-7107, 2000. PubMed ID: 10888650. Show all entries for this paper.

Pinter1989 A. Pinter, W. J. Honnen, S. A. Tilley, C. Bona, H. Zaghouani, M. K. Gorny, and S. Zolla-Pazner. Oligomeric Structure of gp41, the Transmembrane Protein of Human Immunodeficiency Virus Type 1. J. Virol., 63:2674-2679, 1989. PubMed ID: 2786089. Show all entries for this paper.

Poignard1996b P. Poignard, T. Fouts, D. Naniche, J. P. Moore, and Q. J. Sattentau. Neutralizing antibodies to human immunodeficiency virus type-1 gp120 induce envelope glycoprotein subunit dissociation. J. Exp. Med., 183:473-484, 1996. Binding of Anti-V3 and the CD4I neutralizing MAbs induces shedding of gp120 on cells infected with the T-cell line-adapted HIV-1 molecular clone Hx10. This was shown by significant increases of gp120 in the supernatant, and exposure of a gp41 epitope that is masked in the oligomer. MAbs binding either to the V2 loop or to CD4BS discontinuous epitopes do not induce gp120 dissociation. This suggests HIV neutralization probably is caused by several mechanisms, and one of the mechanisms may involve gp120 dissociation. PubMed ID: 8627160. Show all entries for this paper.

Pollara2013 Justin Pollara, Mattia Bonsignori, M. Anthony Moody, Marzena Pazgier, Barton F. Haynes, and Guido Ferrari. Epitope Specificity of Human Immunodeficiency Virus-1 Antibody Dependent Cellular Cytotoxicity (ADCC) Responses. Curr. HIV Res., 11(5):378-387, Jul 2013. PubMed ID: 24191939. Show all entries for this paper.

Robinson1991 W. E. Robinson, M. K. Gorny, J.-Y. Xu, W. M. Mitchell, and S. Zolla-Pazner. Two Immunodominant Domains of gp41 Bind Antibodies Which Enhance Human Immunodeficiency Virus Type 1 Infection In Vitro. J. Virol., 65:4169-4176, 1991. PubMed ID: 2072448. Show all entries for this paper.

Sattentau1991 Q. J. Sattentau and J. P. Moore. Conformational Changes Induced in the Human Immunodeficiency Virus Envelope Glycoprotein by Soluble CD4 Binding. J. Exp. Med., 174:407-415, 1991. sCD4 binding to gp120 induces conformational changes within envelope oligomers. This was measured on HIV-1-infected cells by the increased binding of gp120/V3 loop specific MAbs, and on the surface of virions by increased cleavage of the V3 loop by an exogenous proteinase. PubMed ID: 1713252. Show all entries for this paper.

Sattentau1995 Q. J. Sattentau, S. Zolla-Pazner, and P. Poignard. Epitope Exposure on Functional, Oligomeric HIV-1 gp41 Molecules. Virology, 206:713-717, 1995. Most gp41 epitopes are masked when associated with gp120 on the cell surface. Weak binding of anti-gp41 MAbs can be enhanced by treatment with sCD4. MAb 2F5 binds to a membrane proximal epitope which binds in the presence of gp120 without sCD4. PubMed ID: 7530400. Show all entries for this paper.

Sheppard2007a Neil C. Sheppard, Sarah L. Davies, Simon A. Jeffs, Sueli M. Vieira, and Quentin J. Sattentau. Production and Characterization of High-Affinity Human Monoclonal Antibodies to Human Immunodeficiency Virus Type 1 Envelope Glycoproteins in a Mouse Model Expressing Human Immunoglobulins. Clin. Vaccine Immunol., 14(2):157-167, Feb 2007. PubMed ID: 17167037. Show all entries for this paper.

Spear1993 G. T. Spear, D. M. Takefman, B. L. Sullivan, A. L. Landay, and S. Zolla-Pazner. Complement activation by human monoclonal antibodies to human immunodeficiency virus. J. Virol., 67:53-59, 1993. This study looked at the ability of 16 human MAbs to activate complement. MAbs directed against the V3 region could induce C3 deposition on infected cells and virolysis of free virus, but antibodies to the CD4BS and C-terminal region and two regions in gp41 could induce no complement mediated effects. Pre-treatment with sCD4 could increase complement-mediated effects of anti-gp41 MAbs, but decreased the complement-mediated effects of V3 MAbs. Anti-gp41 MAbs were able to affect IIIB but not MN virolysis, suggesting spontaneous shedding of gp120 on IIIB virions exposes gp41 epitopes. IgG isotype did not appear to have an effect on virolysis or C3 deposition. PubMed ID: 7677959. Show all entries for this paper.

Stamatatos1997 L. Stamatatos, S. Zolla-Pazner, M. K. Gorny, and C. Cheng-Mayer. Binding of Antibodies to Virion-Associated gp120 Molecules of Primary-Like Human Immunodeficiency Virus Type 1 (HIV-1) Isolates: Effect on HIV-1 Infection of Macrophages and Peripheral Blood Mononuclear Cells. Virology, 229:360-369, 1997. PubMed ID: 9126249. Show all entries for this paper.

Till1989 M. A. Till, S. Zolla-Pazner, M. K. Gorny, J. W. Uhr, and E. S. Vitetta. Human Immunodeficiency Virus-Infected T Cells and Monocytes Are Killed by Monoclonal Human Anti-gp41 Antibodies Coupled to Ricin A Chain. Proc. Natl. Acad. Sci. U.S.A., 86:1987-1991, 1989. PubMed ID: 2538826. Show all entries for this paper.

Tyler1990 D. S. Tyler, S. D. Stanley, S. Zolla-Pazner, M. K. Gorny, P. P. Shadduck, A. J. Langlois, T. J. Matthews, D. P. Bolognesi, T. J. Palker, and K. J. Weinhold. Identification of sites within gp41 that serve as targets for antibody-dependent cellular cytotoxicity by using human monoclonal antibodies. J. Immunol., 145:3276-3282, 1990. PubMed ID: 1700004. Show all entries for this paper.

Usami2005 Osamu Usami, Peng Xiao, Hong Ling, Yi Liu, Tadashi Nakasone, and Toshio Hattori. Properties of Anti-gp41 Core Structure Antibodies, Which Compete with Sera of HIV-1-Infected Patients. Microbes Infect., 7(4):650-657, Apr 2005. PubMed ID: 15823513. Show all entries for this paper.

Verrier2001 F. Verrier, A. Nadas, M. K. Gorny, and S. Zolla-Pazner. Additive effects characterize the interaction of antibodies involved in neutralization of the primary dualtropic human immunodeficiency virus type 1 isolate 89.6. J. Virol., 75(19):9177--86, Oct 2001. URL: http://jvi.asm.org/cgi/content/full/75/19/9177. PubMed ID: 11533181. Show all entries for this paper.

Vincent2008 Nadine Vincent, Amadou Kone, Blandine Chanut, Frédéric Lucht, Christian Genin, and Etienne Malvoisin. Antibodies Purified from Sera of HIV-1-Infected Patients by Affinity on the Heptad Repeat Region 1/Heptad Repeat Region 2 Complex of gp41 Neutralize HIV-1 Primary Isolates. AIDS, 22(16):2075-2085, 18 Oct 2008. PubMed ID: 18832871. Show all entries for this paper.

Vincent2012 Nadine Vincent and Etienne Malvoisin. Ability of Antibodies Specific to the HIV-1 Envelope Glycoprotein to Block the Fusion Inhibitor T20 in a Cell-Cell Fusion Assay. Immunobiology, 217(10):943-950, Oct 2012. PubMed ID: 22387075. Show all entries for this paper.

Xu1991 J.-Y. Xu, M. K. Gorny, T. Palker, S. Karwowska, and S. Zolla-Pazner. Epitope mapping of two immunodominant domains of gp41, the transmembrane protein of human immunodeficiency virus type 1, using ten human monoclonal antibodies. J. Virol., 65:4832-4838, 1991. The immunodominance of linear epitope in the region 590-600 of gp41 (cluster I) was established, and a second conformational epitope was mapped that reacted with a region between amino acids 644 and 663 (cluster II). Titration experiments showed that there was 100-fold more antibody to cluster I than cluster II in patient sera. PubMed ID: 1714520. Show all entries for this paper.

Yates2018 Nicole L. Yates, Allan C. deCamp, Bette T. Korber, Hua-Xin Liao, Carmela Irene, Abraham Pinter, James Peacock, Linda J. Harris, Sheetal Sawant, Peter Hraber, Xiaoying Shen, Supachai Rerks-Ngarm, Punnee Pitisuttithum, Sorachai Nitayapan, Phillip W. Berman, Merlin L. Robb, Giuseppe Pantaleo, Susan Zolla-Pazner, Barton F. Haynes, S. Munir Alam, David C. Montefiori, and Georgia D. Tomaras. HIV-1 Envelope Glycoproteins from Diverse Clades Differentiate Antibody Responses and Durability among Vaccinees. J. Virol., 92(8), 15 Apr 2018. PubMed ID: 29386288. Show all entries for this paper.

Yuan2009 Wen Yuan, Xing Li, Marta Kasterka, Miroslaw K. Gorny, Susan Zolla-Pazner, and Joseph Sodroski. Oligomer-Specific Conformations of the Human Immunodeficiency Virus (HIV-1) gp41 Envelope Glycoprotein Ectodomain Recognized by Human Monoclonal Antibodies. AIDS Res. Hum. Retroviruses, 25(3):319-328, Mar 2009. PubMed ID: 19292593. Show all entries for this paper.

Zwick2001b M. B. Zwick, A. F. Labrijn, M. Wang, C. Spenlehauer, E. O. Saphire, J. M. Binley, J. P. Moore, G. Stiegler, H. Katinger, D. R. Burton, and P. W. Parren. Broadly neutralizing antibodies targeted to the membrane-proximal external region of human immunodeficiency virus type 1 glycoprotein gp41. J. Virol., 75(22):10892--905, Nov 2001. URL: http://jvi.asm.org/cgi/content/full/75/22/10892. PubMed ID: 11602729. Show all entries for this paper.


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