HIV-1 autoreactive antibodies: are they good or bad for HIV-1 prevention?

Haynes, Barton F.; Nicely, Nathan I.; Alam, S. Munir

doi:10.1038/nsmb0510-543

Cited by 18 publications

(18 citation statements)

References 24 publications

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“…51 Recently, it was also shown that HIV envelope reactive antibodies isolated from ‘elite controllers’ of infection were polyreactive and that heteroligation to gp120 and self-antigen can increase the apparent affinity of the antibodies for HIV. 19 The preponderance of peripheral auto/polyreactive antibodies in naïve and germ-free hNSG mice that also show binding to HIV envelope proteins may provide a model in which the generation and origins of protective antibody responses against HIV can be investigated.…”

Section: Discussionmentioning

confidence: 99%

Human B-cell ontogeny in humanized NOD/SCID γcnull mice generates a diverse yet auto/poly- and HIV-1-reactive antibody repertoire

et al. 2012

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Characterization of the human antibody (Ab) repertoire in mouse models of the human immune system is essential to establish their relevance in translational studies. Single human B-cells were sorted from bone marrow and periphery of humanized NOD/SCID γcnull mice at 8–10 months post-engraftment with human cord blood-derived CD34+ stem cells. Human immunoglobulin variable heavy (VH) and kappa (Vκ) genes were amplified, cognate VH-Vκ gene-pairs assembled as single-chain variable fragment-Fc antibodies (scFvFcs) and functional studies performed. Although overall distribution of VH genes approximated the normal human Ab repertoire, analysis of the VH-third complementarity determining regions (H-CDR3) in the mature B-cell subset demonstrated an increase in length and positive charges suggesting autoimmune characteristics. Additionally, >70% of Vκ sequences utilized Vκ4-1, a germline gene associated with autoimmunity. The mature B-cell subset-derived scFvFcs displayed the highest frequency of autoreactivity and polyspecificity, suggesting defects in checkpoint control mechanisms. Furthermore, these scFvFcs demonstrated binding to recombinant HIV envelope corroborating previous observations of poly/autoreactivity in anti-HIVgp140 antibodies. These data lend support to the hypothesis that anti-HIV BnAbs may be derived from auto/polyspecific Abs that escaped immune elimination and that the hNSG mouse could provide a new experimental platform for studying the origin of anti-HIV neutralizing Ab responses.

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Section: Discussionmentioning

confidence: 99%

Human B-cell ontogeny in humanized NOD/SCID γcnull mice generates a diverse yet auto/poly- and HIV-1-reactive antibody repertoire

et al. 2012

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“…Also in the case of HIV, VH1-69 neutralizing antibodies have been associated to several drawbacks [65]. Unlike HCV, in which autoreactivity is mediated by VH3-23 and VH3-21 antibodies, whose synthesis results from VH1-69 Abs overproduction, anti-HIV VH1-69 antibodies binding the MPER are directly responsible for autoreactivity.…”

Section: The Dark Side Of Vh1-69 Abs: Autoimmune Disordersmentioning

confidence: 99%

Virus-induced preferential antibody gene-usage and its importance in humoral autoimmunity

Cappelletti

Clementi

Mancini

et al. 2015

Seminars in Immunology

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“…Different studies have suggested that antibody polyreactivity contributes to neutralization of HIV-1 (24,27,31,(55)(56)(57)(58). Several mechanisms have been proposed to explain the role of antibody polyreactivity in HIV-1 neutralization.…”

Section: F425mentioning

confidence: 99%

A Cryptic Polyreactive Antibody Recognizes Distinct Clades of HIV-1 Glycoprotein 120 by an Identical Binding Mechanism

Dimitrov

Planchais

Scheel

et al. 2014

Journal of Biological Chemistry

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Background: Polyreactive antibodies can efficiently neutralize HIV. Results: Heme induces polyreactivity of a human antibody, which recognizes distinct gp120 clades by an identical binding mechanism. Conclusion: Antigen-binding promiscuity of a polyreactive antibody allows recognition of antigen with high molecular heterogeneity. Significance: Characterization of the interaction of polyreactive antibodies with envelope proteins of HIV reveals novel strategies for control of the virus.

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HIV-1 autoreactive antibodies: are they good or bad for HIV-1 prevention?

Abstract: A new crystal structure of an anti–HIV-1 envelope antibody bound to an envelope–receptor complex shows the antibody binding both the HIV-1 envelope and the CD4 receptor, raising the question of what the role of antibody autoreactivity in host responses to HIV-1 may be.

Cited by 18 publications

References 24 publications

Human B-cell ontogeny in humanized NOD/SCID γcnull mice generates a diverse yet auto/poly- and HIV-1-reactive antibody repertoire

Human B-cell ontogeny in humanized NOD/SCID γcnull mice generates a diverse yet auto/poly- and HIV-1-reactive antibody repertoire

Virus-induced preferential antibody gene-usage and its importance in humoral autoimmunity

A Cryptic Polyreactive Antibody Recognizes Distinct Clades of HIV-1 Glycoprotein 120 by an Identical Binding Mechanism

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