A cryptic polyreactive antibody recognizes distinct clades of HIV-1 gp120 by an identical binding mechanism [Protein Structure and Folding]
May 6th, 2014 by Dimitrov, J. D., Planchais, C., Scheel, T., Ohayon, D., Mesnage, S., Berek, C., Kaveri, S. V., Lacroix-Desmazes, S.
Polyreactive antibodies play an important role for neutralization of human immunodeficiency virus (HIV). In addition to intrinsically polyreactive antibodies, the immune repertoires of healthy individuals contain 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 gp120 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 behaviour upon interaction with distinct variants of gp120. The present work 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.