title: A cryptic polyreactive antibody recognizes distinct clades of HIV-1 glycoprotein 120 by an identical binding mechanism.
abstract: Polyreactive antibodies play an important role for neutralization of human immunodeficiency virus (HIV). In addition to intrinsic polyreactive antibodies, the immune system of healthy individuals contains antibodies with cryptic polyreactivity. These antibodies acquire promiscuous antigen binding potential post-translationally, after exposure to various redox-active substances such as reactive oxygen species, iron ions, and heme. Here, we characterized the interaction of a prototypic human antibody that acquires binding potential to glycoprotein (gp) 120 after exposure to heme. The kinetic and thermodynamic analyses of interaction of the polyreactive antibody with distinct clades of gp120 demonstrated that the antigen-binding promiscuity of the antibody compensates for the molecular heterogeneity of the target antigen. Thus, the polyreactive antibody recognized divergent gp120 clades with similar values of the binding kinetics and quantitatively identical changes in the activation thermodynamic parameters. Moreover, this antibody utilized the same type of noncovalent forces for formation of complexes with gp120. In contrast, HIV-1-neutralizing antibodies isolated from HIV-1-infected individuals, F425 B4a1 and b12, demonstrated different binding behavior upon interaction with distinct variants of gp120. This study contributes to a better understanding of the physiological role and binding mechanism of antibodies with cryptic polyreactivity. Moreover, this study might be of relevance for understanding the basic aspects of HIV-1 interaction with human antibodies.
authors.affiliation: From the Centre de Recherche des Cordeliers, Université Pierre et Marie Curie, Unité Mixte de Recherche S 1138, 75006 Paris, France, the Université Paris Descartes, Unité Mixte de Recherche S 1138, Paris, France, INSERM U1138, 75006 Paris, France, jordan.dimitrov@crc.jussieu.fr.
authors.forename: Jordan D
authors.initials: JD
authors.lastname: Dimitrov
authors.affiliation: From the Centre de Recherche des Cordeliers, Université Pierre et Marie Curie, Unité Mixte de Recherche S 1138, 75006 Paris, France, the Université Paris Descartes, Unité Mixte de Recherche S 1138, Paris, France, INSERM U1138, 75006 Paris, France.
authors.forename: Cyril
authors.initials: C
authors.lastname: Planchais
authors.affiliation: the Deutsches Rheuma-Forschungszentrum, Institut der Leibniz-Gemeinschaft, 13092 Berlin, Germany, and.
authors.forename: Tobias
authors.initials: T
authors.lastname: Scheel
authors.affiliation: From the Centre de Recherche des Cordeliers, Université Pierre et Marie Curie, Unité Mixte de Recherche S 1138, 75006 Paris, France, the Université Paris Descartes, Unité Mixte de Recherche S 1138, Paris, France, INSERM U1138, 75006 Paris, France.
authors.forename: Delphine
authors.initials: D
authors.lastname: Ohayon
authors.affiliation: the Krebs Institute, University of Sheffield, Firth Court, Western Bank, Sheffield S10 2TN, United Kingdom.
authors.forename: Stephane
authors.initials: S
authors.lastname: Mesnage
authors.affiliation: the Deutsches Rheuma-Forschungszentrum, Institut der Leibniz-Gemeinschaft, 13092 Berlin, Germany, and.
authors.forename: Claudia
authors.initials: C
authors.lastname: Berek
authors.affiliation: From the Centre de Recherche des Cordeliers, Université Pierre et Marie Curie, Unité Mixte de Recherche S 1138, 75006 Paris, France, the Université Paris Descartes, Unité Mixte de Recherche S 1138, Paris, France, INSERM U1138, 75006 Paris, France.
authors.forename: Srinivas V
authors.initials: SV
authors.lastname: Kaveri
authors.affiliation: From the Centre de Recherche des Cordeliers, Université Pierre et Marie Curie, Unité Mixte de Recherche S 1138, 75006 Paris, France, the Université Paris Descartes, Unité Mixte de Recherche S 1138, Paris, France, INSERM U1138, 75006 Paris, France.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Lacroix-Desmazes
mesh_terms: D000911:Antibodies, Monoclonal / Q000737:chemistry* / Q000276:immunology; D057134:Antibodies, Neutralizing / Q000737:chemistry* / Q000276:immunology; D001666:Binding Sites, Antibody; D015483:HIV Antibodies / Q000737:chemistry* / Q000276:immunology; D015699:HIV Envelope Protein gp120 / Q000737:chemistry* / Q000276:immunology; D015658:HIV Infections / Q000276:immunology; D015497:HIV-1 / Q000737:chemistry* / Q000276:immunology; D006801:Humans; D007700:Kinetics; D013816:Thermodynamics
chemical_list: D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; C514793:gp120 protein, Human immunodeficiency virus 1
keywords: Antibody; Antibody Polyreactivity; HIV-1 Protease; Heme; Protein-Protein Interaction; Thermodynamics; gp120