Search Antibody Database

Found 1 matching record:

Displaying record number 1347

Download this epitope record as JSON.

MAb ID	2158
HXB2 Location	Env	Env Epitope Map
Author Location	gp120( LAI)
Research Contact	Susan Zolla-Pazner (Zollas01@mcrcr6.med.nyu) (NYU Med. Center)
Epitope	(Discontinuous epitope)
Subtype	B
Ab Type	gp120 V2 // V2 glycan(V2g) // V2 apex
Neutralizing	P (tier 1) View neutralization details
Contacts and Features	View contacts and features
Species (Isotype)	human(IgG1κ)
Patient
Immunogen
Keywords	antibody binding site, binding affinity, co-receptor, glycosylation, neutralization, structure, vaccine antigen design, vaccine-induced immune responses, variant cross-reactivity

Notes

Showing 12 of 12 notes.

2158: The authors selected an optimal panel of diverse HIV-1 envelope glycoproteins to represent the antigenic diversity of HIV globally in order to be used as antigen candidates. The selection was based on genetic and geographic diversity, and experimentally and computationally evaluated humoral responses. The eligibility of the envelopes as vaccine candidates was evaluated against a panel of antibodies for breadth, affinity, binding and durability of vaccine-elicited responses. The antigen panel was capable of detecting the spectrum of V2-specific antibodies that target epitopes from the V2 strand C (V2p), the integrin binding motif in V2 (V2i), and the quaternary epitope at the apex of the trimer (V2q). Yates2018 (vaccine antigen design, vaccine-induced immune responses, binding affinity)
2158: Env from of a highly neutralization-resistant isolate, CH120.6, was shown to be very stable and conformationally-homogeneous. Its gp140 trimer retains many antigenic properties of the intact Env, while its monomeric gp120 exposes more epitopes. Thus trimer organization and stability are important determinants for occluding epitopes and conferring resistance to antibodies. Among a panel of 21 mAbs, CH120.6 was resistant to neutralization by all non-neutralizing and strain-specific mAbs (including 2158), regardless of the location of their epitopes. It was weakly neutralized by several broadly-neutralizing mAbs (VRC01, NIH45-46, 12A12, PG9, PG16, PGT128, 4E10, and 10E8), and well neutralized by only 2 (PGT145 and 10-1074). Cai2017 (neutralization)
2158: Two stable homogenous gp140 Env trimer spikes, Clade A 92UG037.8 Env and Clade C C97ZA012 Env, were identified. 293T cells stably transfected with either presented fully functional surface timers, 50% of which were uncleaved. A panel of neutralizing and non-neutralizing Abs were tested for binding to the trimers. Non-neutralizing V2 Ab 2158 did not bind cell surface or neutralize 92UG037.8 HIV-1 isolate though it did bind gp160 minus its C-terminus (gp160ΔCT) moderately, and was able to bind weakly in the presence of sCD4. Chen2015 (neutralization, binding affinity)
2158: The study compared various factors affecting the accessibility of epitopes for antibodies targeting the V2 integrin (V2i) region, versus the V3 region. CD4 treament of BaL and JRFL pseudoviruses increased their neutralization sensitivity to V3 MAbs, but not to V2i MAbs. Viruses grown in a glycosidase inhibitor were more sensitive to neutralization by V3, but not V2i, MAbs. Increasing the time of virus-MAb interaction increased virus neutralization by some V2i MAbs and all V3 MAbs. The structural dynamics of V2i and V3 epitopes has important effects in neutralization. The V2i MAbs tested were: 697, 830A, 1357, 1361, 1393, 2158, and 2297. Upadhyay2014 (glycosylation, neutralization)
2158: This study characterized the Elisa cross-reactivity, neutralization, and Ig variable genes of a panel of 7 anti-V2 mAbs: 1361, 1393A, 1357, 697, 830A, 2158, and 2297. Despite sequence variability, the 7 mAbs recognize conserved immunologic features of V2, with 6 of them targeting similar epitopes. The crystal structure of the mAb 697 binding site was determined. Gorny2012 (neutralization)
2158: This study solved the crystal structure of mAb 2158 and -constructed a full-length model of V1V2. Structure, modeling and mutagenesis assays were used to define the conformational epitope K168, K169, A172, Y173, L193, P179, D180, V181, which includes the integrin binding site in V2. Spurrier2014 (antibody binding site, structure)
2158: This study analyzed the neutralization sensitivity of sequential HIV-1 primary isolates during their natural evolution in 5 subtype B and CRF02_AG HIV-1 infected drug naive individuals to 13 anti-HIV-1 MAbs (including this MAb) directed at epitopes in the V2, V3, CD4bd and carbohydrates. Patient viruses evolved to become more sensitive to neutralization by MAbs directed at epitopes at V2, V3 and CDbd, indicating that cross sectional studies are inadequate to define the neutralization spectrum of MAb neutralization with primary HIV-1 isolates. Haldar2011 (neutralization)
2158: 2158 bound very weakly to SF162 wild type and not at all to SF162 mutant, carrying only the monomeric form of the Env protein. Kimura2009 (binding affinity)
2158: gp120 in complex with 2158 had higher reactivity with 694/98-D compared to the uncomplexed gp120. Hioe2009 (binding affinity)
2158: V1V2 was determined to be the region that conferred the neutralization phenotype differences between two R5-tropic primary HIV-1 isolates, JRFL and SF162. JRFL is resistant to neutralization by many sera and MAbs, while SF162 is sensitive. All MAbs tested, anti-V3, -V2, -CD4BS, and -CD4i, (except the broadly neutralizing MAbs IgG1b12, 2F5, and 2G12, which neutralized both strains), neutralized the SF162 pseudotype but not JRFL, and chimeras that exchanged the V1V2 loops transferred the neutralization phenotype. Three anti-V2 MAb were tested -- both 2158 and 830A bound more strongly to JRFL, but neutralized SF162, and not neutralize JRFL. Thus V2 domains are better neutralization targets in SF162. Pinter2004 (variant cross-reactivity)
2158: The role of serine proteases on HIV infection was explored. Trypsin decreased the binding of most Env MAb tested and diminished cell fusion of H9 cells infected with HIV-1 LAI virus (H9/IIIB) to MAGI cells. In contrast, thrombin increased the binding of MAbs to gp120 epitopes near the CD4 and CCR5 binding sites, and increased cell fusion. Binding of 17b and F105 was decreased by trypsin, but increased by thrombin. V2 MAbs 830A and 2158 were decreased by trypsin, unaffected by thrombin. Thrombin may increase HIV-induced cell fusion in blood by causing a conformational activating shift in gp120. Ling2004 (antibody binding site)
2158: A pseudotyping assay showed that an X4 V3 loop peptide could enhance infectivity of X4 virus, R5 and R5X4 V3 loops peptides could enhance infectivity of an R5 virus, and R5X4 peptides could enhance infectivity of an R5X4 virus. Neither R5 nor R5X4 peptides influenced binding of CD4BS MAbs F105 and Ig1Gb12, but did increase binding of CD4i MAb 17b. Of three V2 MAbs, only 830A, not 2158 or 1357, was enhanced by V3 peptide binding. Ling2002 (antibody binding site, co-receptor)

References

Showing 12 of 12 references.

Cai2017 Yongfei Cai, Selen Karaca-Griffin, Jia Chen, Sai Tian, Nicholas Fredette, Christine E. Linton, Sophia Rits-Volloch, Jianming Lu, Kshitij Wagh, James Theiler, Bette Korber, Michael S. Seaman, Stephen C. Harrison, Andrea Carfi, and Bing Chen. Antigenicity-Defined Conformations of an Extremely Neutralization-Resistant HIV-1 Envelope Spike. Proc. Natl. Acad. Sci. U.S.A., 114(17):4477-4482, 25 Apr 2017. PubMed ID: 28396421. Show all entries for this paper.

Chen2015 Jia Chen, James M. Kovacs, Hanqin Peng, Sophia Rits-Volloch, Jianming Lu, Donghyun Park, Elise Zablowsky, Michael S. Seaman, and Bing Chen. Effect of the Cytoplasmic Domain on Antigenic Characteristics of HIV-1 Envelope Glycoprotein. Science, 349(6244):191-195, 10 Jul 2015. PubMed ID: 26113642. Show all entries for this paper.

Gorny2012 Miroslaw K. Gorny, Ruimin Pan, Constance Williams, Xiao-Hong Wang, Barbara Volsky, Timothy O'Neal, Brett Spurrier, Jared M. Sampson, Liuzhe Li, Michael S. Seaman, Xiang-Peng Kong, and Susan Zolla-Pazner. Functional and Immunochemical Cross-Reactivity of V2-Specific Monoclonal Antibodies from HIV-1-Infected Individuals. Virology, 427(2):198-207, 5 Jun 2012. PubMed ID: 22402248. Show all entries for this paper.

Haldar2011 Bijayesh Haldar, Sherri Burda, Constance Williams, Leo Heyndrickx, Guido Vanham, Miroslaw K. Gorny, and Phillipe Nyambi. Longitudinal Study of Primary HIV-1 Isolates in Drug-Naïve Individuals Reveals the Emergence of Variants Sensitive to Anti-HIV-1 Monoclonal Antibodies. PLoS One, 6(2):e17253, 2011. PubMed ID: 21383841. Show all entries for this paper.

Hioe2009 Catarina E. Hioe, Maria Luisa Visciano, Rajnish Kumar, Jianping Liu, Ethan A. Mack, Rachel E. Simon, David N. Levy, and Michael Tuen. The Use of Immune Complex Vaccines to Enhance Antibody Responses against Neutralizing Epitopes on HIV-1 Envelope gp120. Vaccine, 28(2):352-360, 11 Dec 2009. PubMed ID: 19879224. Show all entries for this paper.

Kimura2009 Tetsuya Kimura, Xiao-Hong Wang, Constance Williams, Susan Zolla-Pazner, and Miroslaw K. Gorny. Human Monoclonal Antibody 2909 Binds to Pseudovirions Expressing Trimers but not Monomeric HIV-1 Envelope Proteins. Hum. Antibodies, 18(1-2):35-40, 2009. PubMed ID: 19478397. Show all entries for this paper.

Ling2002 Hong Ling, Xiao-Yan Zhang, Osamu Usami, and Toshio Hattori. Activation of gp120 of Human Immunodeficiency Virus by Their V3 Loop-Derived Peptides. Biochem. Biophys. Res. Commun., 297(3):625-631, 27 Sep 2002. PubMed ID: 12270140. 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.

Pinter2004 Abraham Pinter, William J. Honnen, Yuxian He, Miroslaw K. Gorny, Susan Zolla-Pazner, and Samuel C. Kayman. The V1/V2 Domain of gp120 Is a Global Regulator of the Sensitivity of Primary Human Immunodeficiency Virus Type 1 Isolates to Neutralization by Antibodies Commonly Induced upon Infection. J. Virol., 78(10):5205-5215, May 2004. PubMed ID: 15113902. Show all entries for this paper.

Spurrier2014 Brett Spurrier, Jared Sampson, Miroslaw K. Gorny, Susan Zolla-Pazner, and Xiang-Peng Kong. Functional Implications of the Binding Mode of a Human Conformation-Dependent V2 Monoclonal Antibody against HIV. J. Virol., 88(8):4100-4112, Apr 2014. PubMed ID: 24478429. Show all entries for this paper.

Upadhyay2014 Chitra Upadhyay, Luzia M. Mayr, Jing Zhang, Rajnish Kumar, Miroslaw K. Gorny, Arthur Nádas, Susan Zolla-Pazner, and Catarina E. Hioe. Distinct Mechanisms Regulate Exposure of Neutralizing Epitopes in the V2 and V3 Loops of HIV-1 Envelope. J. Virol., 88(21):12853-12865, Nov 2014. PubMed ID: 25165106. 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.