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MAb ID	4-79
HXB2 Location	Env	Env Epitope Map
Author Location	gp120
Epitope
Ab Type
Neutralizing
Species (Isotype)	human(IgG)
Patient	Patient 4
Immunogen	HIV-1 infection
Keywords	antibody binding site, antibody generation, antibody polyreactivity, antibody sequence, binding affinity, kinetics, neutralization, optimal epitope, variant cross-reactivity

Notes

Showing 3 of 3 notes.

4-79: 134 unique anti-gp140 and 52 control non-gp140 reactive antibodies were studied for polyreactivity and its effect on binding affinity and neutralization. 75% of antibodies were polyreactive. 4-79 is sensitive to neutralization and binds to ssDNA, dsDNA, LPS (lipopolysaccharide), insulin, ANA (antinuclear antibody) and CL (cardiolipin). Somatically Mutated and Reverted 4-79 bind with gp140, dsDNA, ssDNA, Insulin, LPS (lipopolysaccharide) and Hep2 and are polyreactive but only Somatically Mutated 4-79 is sensitive to neutralization. Somatically Mutated 4-79 neutralizes clade A and clade B (SF162.LS) viruses whereas Reverted 4-79 does not neutralize any virus. Mouquet2010 (neutralization, binding affinity, antibody polyreactivity)
4-79: Substitutions in the CD4bs (E370A and/or D368A) or in close proximity to the CD4bs (N276A, R480A and Y384A) reduced binding of b12 but had no effect on binding activity of 4-79, indicating that binding characteristics of the anti-CD4bs Ab and anti-core Abs are distinct. Three mutations, D747A, M475A and R476A, had no effect on b12 binding but two (D474A and R476A) reduced binding of anti-core 4-79 MAb. These three residues were shown to be required for optimal viral infectivity. In addition, 4-79 bound to gp160 trimer lacking the cytoplasmic domain and to gp140 with high affinity but, unlike b12, did not bind to gp160 or gp140 with the three mutations. These results indicate that anti-core Abs recognize a conformational epitope including the α5 helix at the outer-domain-inner-domain junction of gp120. The epitope was highly conserved across different HIV-1 isolates. Pietzsch2010a (antibody binding site, optimal epitope, variant cross-reactivity, kinetics, binding affinity)
4-79: This Ab was cloned from HIV envelope-binding memory B cells from a patient with broadly neutralizing Abs in serum, and was reactive to gp120 core, recognizing epitope in the vicinity of the CD4bs and the CD4i site. 4-79 was shown to have high affinity for gp140 and it competed with CD4bs and CD4i Abs for binding to gp140. 4-79 neutralized 2/5 Tier 1 and none of the Tier 2 viruses, and did not show broad serum-neutralizing activity. In total, 433 Abs were isolated from 6 patients, with neutralizing activity directed against several epitopes on gp120. Tier-2 neutralization was observed only with mixtures of MAbs, but only at high concentrations. Scheid2009 (antibody generation, neutralization, kinetics, binding affinity, antibody sequence)

References

Showing 3 of 3 references.

Isolation Paper
Scheid2009 Johannes F. Scheid, Hugo Mouquet, Niklas Feldhahn, Michael S. Seaman, Klara Velinzon, John Pietzsch, Rene G. Ott, Robert M. Anthony, Henry Zebroski, Arlene Hurley, Adhuna Phogat, Bimal Chakrabarti, Yuxing Li, Mark Connors, Florencia Pereyra, Bruce D. Walker, Hedda Wardemann, David Ho, Richard T. Wyatt, John R. Mascola, Jeffrey V. Ravetch, and Michel C. Nussenzweig. Broad Diversity of Neutralizing Antibodies Isolated from Memory B Cells in HIV-Infected Individuals. Nature, 458(7238):636-640, 2 Apr 2009. PubMed ID: 19287373. Show all entries for this paper.

Mouquet2010 Hugo Mouquet, Johannes F. Scheid, Markus J. Zoller, Michelle Krogsgaard, Rene G. Ott, Shetha Shukair, Maxim N. Artyomov, John Pietzsch, Mark Connors, Florencia Pereyra, Bruce D. Walker, David D. Ho, Patrick C. Wilson, Michael S. Seaman, Herman N. Eisen, Arup K. Chakraborty, Thomas J. Hope, Jeffrey V. Ravetch, Hedda Wardemann, and Michel C. Nussenzweig. Polyreactivity Increases the Apparent Affinity of Anti-HIV Antibodies by Heteroligation. Nature, 467(7315):591-595, 30 Sep 2010. PubMed ID: 20882016. Show all entries for this paper.

Pietzsch2010a John Pietzsch, Johannes F. Scheid, Hugo Mouquet, Florian Klein, Michael S. Seaman, Mila Jankovic, Davide Corti, Antonio Lanzavecchia, and Michel C. Nussenzweig. Human Anti-HIV-Neutralizing Antibodies Frequently Target a Conserved Epitope Essential for Viral Fitness. J. Exp. Med., 207(9):1995-2002, 30 Aug 2010. PubMed ID: 20679402. Show all entries for this paper.