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Displaying record number 1094

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MAb ID	2412
HXB2 Location	Env	Env Epitope Map
Author Location	gp120 (V3)(gp120 JRCSF)
Research Contact	Susan Zolla-Pazner (Zollas01@mcrcr6.med.nyu) (NYU Med. Center)
Epitope
Subtype	B
Ab Type	gp120 V3 // V3 glycan (V3g)
Neutralizing	P
Species (Isotype)	human(IgG1λ)
Patient
Immunogen	HIV-1 infection
Keywords	antibody binding site, antibody generation, antibody sequence, binding affinity, neutralization, review, subtype comparisons, variant cross-reactivity

Notes

Showing 6 of 6 notes.

2412: The Ig usage for variable heavy chain of this Ab was as follows: IGHV:2-5*04, IGHD:3-22, D-RF:2, IGHJ:4. There was a preferential usage of the VH5-51 gene segment for V3 Abs. The usage of the VH4 family for the V3 Abs was restricted to only one gene segment, VH4-59, and the VH3 gene family was used at a significantly lower level by these Abs. The V3 Abs preferentially used the JH3 and D2-15 gene segments. Gorny2009 (antibody sequence)
2412: This Ab was shown to neutralize SF162 and the neutralization sensitivity increased in the SF162 variant with a JR-FL V3 loop, SF162(JR-FL V3). In contrast, no neutralization was observed of the SF162(JR-FL V1/V2) variant and was somewhat restored in the SF162(JR-FL V1/V2/V3) variant, indicating that the masking of the V1/V2 loop plays a much greater role in restricting neutralization sensitivity than the variations in V3. This Ab was shown to neutralize viruses with V3 sequences from several different subtypes (B, F, and A1) except subtypes C, CRF02_AG, H and CRF01_AE. This Ab failed to neutralize SF162(JR-FL V1/V2) with V3 derived from different HIV-1 clades indicating effective V1/V2-mediated masking of several HIV-1 clades. The effect on the neutralization sensitivity of the residue at the crown of the V3 loop (position 18) was shown to be great for this Ab. Krachmarov2006 (neutralization, variant cross-reactivity, subtype comparisons)
2412: This MAb was derived from plasma from a patient with env clade B virus with the GPGR V3 motif. When cross-reactivity was tested, this Ab bound to the V3subtypeB-fusion protein containing GPGR motif but not to V3subtypeA-fusion protein containing GPGQ motif. This Ab was also shown to be able to neutralize clade B psSF162 (GPGR) but not clade C psMW965 (GPGQ) virus, and three of subtype B but only two of non-B primary isolates. Gorny2006 (neutralization, variant cross-reactivity, binding affinity, subtype comparisons)
2412: V3 MAb neutralization is influenced by retaining the epitope, exposure on the intact virion, mobility during CD4-induced conformational change, and affinity. Anti-V3 MAbs selected using V3 peptides neutralize less effectively than V3 MAbs selected using fusion proteins or gp120, suggesting antigenic conformation is important. This MAb was selected using a JR-CSF fusion protein, and could neutralize 4/13 B clade viruses. Gorny2004 (antibody binding site)
2412: This review provides summaries of Abs that bind to HIV-1 Env. There are many V3 MAbs, many neutralize some TCLA strains, and a subset can also neutralize some primary isolates. The set that can cross-neutralize primary isolates (2182, 2191, 2219, 2412, 2442, 2456) bind V3 but are conformationally senstitive, suggesting some structural conservation despite sequence variation. These MAbs have distinct epitopes relative to 447-52D, a MAb directed at the tip of the V3 loop that also can neutralize many primary isolates. Inter-clade cross-neutralization by these anti-V3 MAbs is reduced. Gorny2003 (antibody binding site, review)
2412: Conformation-dependent anti-V3 loop Abs may be more cross-reactive, so six new V3 MAbs were generated from cells of asymptomatic HIV-1-infected individuals by selection of heterhybridomas using a V3-fusion protein (V3-fp), the HIV-1 JRCSF V3 loop inserted into a truncated murine leukemia virus gp70 -- the six new MAbs all bind to the tip of the V3 loop and cross-compete with the MAb 447-52D and are conformationally sensitive -- MAbs showed cross-clade binding to native, intact virions of clades A(N=2), B(N=4), and F(N=2), limited binding to C(N=3) and D(N=3), and did not bind to CRF01(subtype E, N=2) -- the strength binding was highly correlated with percent neutralization using the ghost cell or PHA blast assay -- five well-characterized MAbs were used as controls: anti-V3 447-52D (anti-V3 MAb for competition and neutralization studies), 654 (anti-CD4BS used as a conformation-sensitive MAb control), 1331A (anti-C5 used as a linear binding site MAb control), MAb 246 (anti-gp41 MAb that bound to primary isolates of all clades) -- 5/6 MAbs were derived from individuals infected in the US, presumably with clade B, and one, 2182, was derived from an individual who was infected abroad with clade A who is presently living in New York city -- 2412 and 2456 were produced from cells obtained from the same individual, while the other MAbs were each generated from different subjects -- 2412 bound to 7/16 of the diverse isolates, and did not bind to any of the clade C, D or CRF01 viruses. Gorny2002 (antibody binding site, antibody generation, variant cross-reactivity, subtype comparisons)

References

Showing 6 of 6 references.

Isolation Paper
Gorny2002 Miroslaw K. Gorny, Constance Williams, Barbara Volsky, Kathy Revesz, Sandra Cohen, Victoria R. Polonis, William J. Honnen, Samuel C. Kayman, Chavdar Krachmarov, Abraham Pinter, and Susan Zolla-Pazner. Human Monoclonal Antibodies Specific for Conformation-Sensitive Epitopes of V3 Neutralize Human Immunodeficiency Virus Type 1 Primary Isolates from Various Clades. J. Virol., 76(18):9035-9045, Sep 2002. PubMed ID: 12186887. 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.

Gorny2004 Miroslaw K. Gorny, Kathy Revesz, Constance Williams, Barbara Volsky, Mark K. Louder, Christopher A. Anyangwe, Chavdar Krachmarov, Samuel C. Kayman, Abraham Pinter, Arthur Nadas, Phillipe N. Nyambi, John R. Mascola, and Susan Zolla-Pazner. The V3 Loop is Accessible on the Surface of Most Human Immunodeficiency Virus Type 1 Primary Isolates and Serves as a Neutralization Epitope. J. Virol., 78(5):2394-2404, Mar 2004. PubMed ID: 14963135. Show all entries for this paper.

Gorny2006 Miroslaw K. Gorny, Constance Williams, Barbara Volsky, Kathy Revesz, Xiao-Hong Wang, Sherri Burda, Tetsuya Kimura, Frank A. J. Konings, Arthur Nádas, Christopher A. Anyangwe, Phillipe Nyambi, Chavdar Krachmarov, Abraham Pinter, and Susan Zolla-Pazner. Cross-Clade Neutralizing Activity of Human Anti-V3 Monoclonal Antibodies Derived from the Cells of Individuals Infected with Non-B Clades of Human Immunodeficiency Virus Type 1. J. Virol., 80(14):6865-6872, Jul 2006. PubMed ID: 16809292. Show all entries for this paper.

Krachmarov2006 C. P. Krachmarov, W. J. Honnen, S. C. Kayman, M. K. Gorny, S. Zolla-Pazner, and Abraham Pinter. Factors Determining the Breadth and Potency of Neutralization by V3-Specific Human Monoclonal Antibodies Derived from Subjects Infected with Clade A or Clade B Strains of Human Immunodeficiency Virus Type 1. J. Virol., 80(14):7127-7135, Jul 2006. PubMed ID: 16809318. 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.