title: Relationship between natural and heme-mediated antibody polyreactivity.
abstract: Polyreactive antibodies represent a considerable fraction of the immune repertoires. Some antibodies acquire polyreactivity post-translationally after interaction with various redox-active substances, including heme. Recently we have demonstrated that heme binding to a naturally polyreactive antibody (SPE7) results in a considerable broadening of the repertoire of recognized antigens. A question remains whether the presence of certain level of natural polyreactivity of antibodies is a prerequisite for heme-induced further extension of antigen binding potential. Here we used a second monoclonal antibody (Hg32) with unknown specificity and absence of intrinsic polyreactivity as a model to study the potential of heme to induce polyreactivity of antibodies. We demonstrated that exposure to heme greatly extends the antigen binding potential of Hg32, suggesting that the intrinsic binding promiscuity is not a prerequisite for the induction of polyreactivity by heme. In addition we compared the kinetics and thermodynamics of the interaction of heme-exposed antibodies with a panel of unrelated antigens. These analyses revealed that the two heme-sensitive antibodies adopt different mechanisms of binding to the same set of antigens. This study contributes to understanding the phenomenon of induced antibody polyreactivity. The data may also be of importance for understanding of physiological and pathological roles of polyreactive antibodies.
authors.affiliation: Stephan Angelov Institute of Microbiology, Bulgarian Academy of Sciences, Sofia 1113, Bulgaria.
authors.forename: Maya
authors.initials: M
authors.lastname: Hadzhieva
authors.affiliation: Stephan Angelov Institute of Microbiology, Bulgarian Academy of Sciences, Sofia 1113, Bulgaria.
authors.forename: Tchavdar
authors.initials: T
authors.lastname: Vassilev
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, UMR_S 1138, Centre de Recherche des Cordeliers, F-75006 Paris, France; INSERM, UMR_S 1138, F-75006 Paris, France; Université Paris Descartes, Sorbonne Paris Cité, UMR_S 1138, F-75006 Paris, France.
authors.forename: Jagadeesh
authors.initials: J
authors.lastname: Bayry
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, UMR_S 1138, Centre de Recherche des Cordeliers, F-75006 Paris, France; INSERM, UMR_S 1138, F-75006 Paris, France; Université Paris Descartes, Sorbonne Paris Cité, UMR_S 1138, F-75006 Paris, France.
authors.forename: Srinivas
authors.initials: S
authors.lastname: Kaveri
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, UMR_S 1138, Centre de Recherche des Cordeliers, F-75006 Paris, France; INSERM, UMR_S 1138, F-75006 Paris, France; Université Paris Descartes, Sorbonne Paris Cité, UMR_S 1138, F-75006 Paris, France.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Lacroix-Desmazes
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, UMR_S 1138, Centre de Recherche des Cordeliers, F-75006 Paris, France; INSERM, UMR_S 1138, F-75006 Paris, France; Université Paris Descartes, Sorbonne Paris Cité, UMR_S 1138, F-75006 Paris, France. Electronic address: jordan.dimitrov@crc.jussieu.fr.
authors.forename: Jordan D
authors.initials: JD
authors.lastname: Dimitrov
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000378:metabolism; D058846:Antibodies, Monoclonal, Murine-Derived / Q000276:immunology / Q000378:metabolism; D000916:Antibody Diversity; D000918:Antibody Specificity / Q000276:immunology*; D000937:Antigen-Antibody Reactions; D006418:Heme / Q000276:immunology*; D055767:Immobilized Proteins / Q000276:immunology / Q000378:metabolism; D007073:Immunoglobulin E / Q000276:immunology / Q000378:metabolism; D007700:Kinetics; D051379:Mice; D011499:Protein Processing, Post-Translational; D051381:Rats; D020349:Surface Plasmon Resonance; D013816:Thermodynamics
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D055767:Immobilized Proteins; D007073:Immunoglobulin E; D006418:Heme
keywords: Antibody polyreactivity; Heme; Immunoglobulins; Thermodynamics