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MAb ID 98-6 (SZ-98.6, 98.6, 98-6D)
HXB2 Location Env
Env Epitope Map
Author Location gp41( HXB2)
Research Contact Susan Zolla-Pazner (, NYU, NY
Epitope (Discontinuous epitope)
Subtype B
Ab Type gp41 cluster II
Species (Isotype) human(IgG2κ)
Patient donor_uncoded_3
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, neutralization, rate of progression, review, structure, subtype comparisons, vaccine antigen design, variant cross-reactivity


Showing 44 of 44 notes.


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.

Alam2008 S. Munir Alam, Richard M. Scearce, Robert J. Parks, Kelly Plonk, Steven G. Plonk, Laura L. Sutherland, Miroslaw K. Gorny, Susan Zolla-Pazner, Stacie VanLeeuwen, M. Anthony Moody, Shi-Mao Xia, David C. Montefiori, Georgia D. Tomaras, Kent J. Weinhold, Salim Abdool Karim, Charles B. Hicks, Hua-Xin Liao, James Robinson, George M. Shaw, and Barton F. Haynes. Human Immunodeficiency Virus Type 1 gp41 Antibodies That Mask Membrane Proximal Region Epitopes: Antibody Binding Kinetics, Induction, and Potential for Regulation in Acute Infection. J. Virol., 82(1):115-125, Jan 2008. PubMed ID: 17942537. Show all entries for this paper.

Andris1991 J. S. Andris, S. Johnson, S. Zolla-Pazner, and J. D. Capra. Molecular characterization of five anti-human immunodeficiency virus type 1 antibody heavy chains reveals extensive somatic mutation typical of an antigen-driven immune response. Proc. Natl. Acad. Sci. U.S.A., 88:7783-7788, 1992. PubMed ID: 1909030. 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.

Forthal1995 D. N. Forthal, G. Landucci, M. K. Gorny, S. Zolla-Pazner, and W. E. Robinson, Jr. Functional Activities of 20 Human Immunodeficiency Virus Type 1 (HIV-1)-Specific Human Monoclonal Antibodies. AIDS Res. Hum. Retroviruses, 11:1095-1099, 1995. A series of tests were performed on 20 human monoclonal antibodies to assess their potential therapeutic utility. Antibodies were tested for potentially harmful complement-mediated antibody enhancing activity (C-ADE), and for potentially beneficial neutralizing activity and antibody dependent cellular cytotoxicity ADCC. PubMed ID: 8554906. Show all entries for this paper.

Frey2010 Gary Frey, Jia Chen, Sophia Rits-Volloch, Michael M. Freeman, Susan Zolla-Pazner, and Bing Chen. Distinct Conformational States of HIV-1 gp41 Are Recognized by Neutralizing and Non-Neutralizing Antibodies. Nat. Struct. Mol. Biol., 17(12):1486-1491, Dec 2010. PubMed ID: 21076402. 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.

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: 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.

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.

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.

Nyambi1998 P. N. Nyambi, M. K. Gorny, L. Bastiani, G. van der Groen, C. Williams, and S. Zolla-Pazner. Mapping of Epitopes Exposed on Intact Human Immunodeficiency Virus Type 1 (HIV-1) Virions: A New Strategy for Studying the Immunologic Relatedness of HIV-1. J. Virol., 72:9384-9391, 1998. 18 human MAbs binding to gp120 and gp41 were tested using a novel assay to test binding to intact HIV-1 virions. The new method involves using MAbs to the host proteins incorporated into virions to bind them to ELIZA plates. Antigenic conservation in epitopes of HIV-1 in clades A, B, D, F, G, and H was studied. MAbs were selected that were directed against V2, V3, CD4bd, C5 or gp41 regions. Antibodies against V2, the CD4BS, and sp41 showed weak and sporadic reactivities, while binding strongly to gp120, suggesting these epitopes are hidden when gp120 is in its native, quaternary structure. PubMed ID: 9765494. 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.

Penn-Nicholson2008 Adam Penn-Nicholson, Dong P. Han, Soon J. Kim, Hanna Park, Rais Ansari, David C. Montefiori, and Michael W. Cho. Assessment of Antibody Responses against gp41 in HIV-1-Infected Patients Using Soluble gp41 Fusion Proteins and Peptides Derived from M Group Consensus Envelope. Virology, 372(2):442-456, 15 Mar 2008. PubMed ID: 18068750. Show all entries for this paper.

Perez2009 Lautaro G. Perez, Matthew R. Costa, Christopher A. Todd, Barton F. Haynes, and David C. Montefiori. Utilization of Immunoglobulin G Fc Receptors by Human Immunodeficiency Virus Type 1: A Specific Role for Antibodies against the Membrane-Proximal External Region of gp41. J. Virol., 83(15):7397-7410, Aug 2009. PubMed ID: 19458010. 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.

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.

Robinson1990a W. E. Robinson, Jr., T. Kawamura, M. K. Gorny, D. Lake, J.-Y. Xu, Y. Matsumoto, T. Sugano, Y. Masuho, W. M. Mitchell, E. Hersh, and S. Zolla-Pazner. Human Monoclonal Antibodies to the Human Immunodeficiency Virus Type 1 (HIV-1) Transmembrane Glycoprotein gp41 Enhance HIV-1 Infection In Vitro. Proc. Natl. Acad. Sci. U.S.A., 87:3185-3189, 1990. Three gp41 MAbs out of 16 Env and Gag MAbs tested enhanced HIV-1 IIIB infection of MT-2 cells. The enhancing antibodies were competitive with the immunodominant epitopes of gp41 recognized by sera from HIV-1 infected subjects. PubMed ID: 2326277. 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.

Shi2010 Wuxian Shi, Jen Bohon, Dong P. Han, Habtom Habte, Yali Qin, Michael W. Cho, and Mark R. Chance. Structural Characterization of HIV gp41 with the Membrane-Proximal External Region. J. Biol. Chem., 285(31):24290-24298, 30 Jul 2010. PubMed ID: 20525690. 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.

Tani1994 Y. Tani, E. Donoghue, S. Sharpe, E. Boone, H. C. Lane, S. Zolla-Pazner, and D. I. Cohen. Enhanced In Vitro Human Immunodeficiency Virus Type 1 Replication in B Cells Expressing Surface Antibody to the TM Env Protein. J. Virol., 68:1942-1950, 1994. The MAb 98-6 was expressed as a surface anti-gp41 monoclonal antibody receptor for gp41 (sIg/gp41) by transfection into a CD4-negative B-cell line. Transfected cells could bind HIV envelope, but could not be infected by HIV-1. When CD4 delivered by retroviral constructs was expressed on these cells, they acquired the ability to replicate HIV-1, and sIg/gp41 specifically enhanced viral replication. PubMed ID: 8107254. Show all entries for this paper.

Taniguchi2000 Y. Taniguchi, S. Zolla-Pazner, Y. Xu, X. Zhang, S. Takeda, and T. Hattori. Human monoclonal antibody 98-6 reacts with the fusogenic form of gp41. Virology, 273(2):333--40, 1 Aug 2000. PubMed ID: 10915604. 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: PubMed ID: 11533181. Show all entries for this paper.

vonBredow2016 Benjamin von Bredow, Juan F. Arias, Lisa N. Heyer, Brian Moldt, Khoa Le, James E. Robinson, Susan Zolla-Pazner, Dennis R. Burton, and David T. Evans. Comparison of Antibody-Dependent Cell-Mediated Cytotoxicity and Virus Neutralization by HIV-1 Env-Specific Monoclonal Antibodies. J. Virol., 90(13):6127-6139, 1 Jul 2016. PubMed ID: 27122574. Show all entries for this paper.

Wisnewski1996 A. Wisnewski, L. Cavacini, and M. Posner. Human antibody variable region gene usage in HIV-1 infection. J. Acquir. Immune Defic. Syndr. Hum. Retrovirol., 11:31-38, 1996. PubMed ID: 8528730. Show all entries for this paper.

Witt2017 Kristen C. Witt, Luis Castillo-Menendez, Haitao Ding, Nicole Espy, Shijian Zhang, John C. Kappes, and Joseph Sodroski. Antigenic Characterization of the Human Immunodeficiency Virus (HIV-1) Envelope Glycoprotein Precursor Incorporated into Nanodiscs. PLoS One, 12(2):e0170672, 2017. PubMed ID: 28151945. 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.

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.

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