Thermodynamic analysis of the binding of 2F5 Fab and IgG to its gp41 epitope reveals a strong influence of the immunoglobulin Fc region on the affinity [Molecular Bases of Disease]

December 3rd, 2013 by Crespillo, S., Casares, S., Mateo, P. L., Conejero-Lara, F.

Immunotherapies and vaccines based on the induction of broadly neutralizing monoclonal antibodies (bNAb) have become outstanding strategies against HIV-1. Diverse bNAbs recognizing different regions of HIV-1 envelope have been identified and extensively studied. However, there is scarce information about the thermodynamics of binding of these bNAbs and their epitopes. We used isothermal titration calorimetry to characterize thermodynamically the interactions between the 2F5 bNAb, in both IgG and Fab forms, and its functional and core epitope peptides. We found that these interactions are enthalpically driven and opposed by a negative entropy change. The highest affinity was found for 2F5-IgG to its functional epitope, indicating that additional interactions involving residues flanking the core epitope contribute strongly to a higher affinity. In addition, the strong influence of the Fc region in the binding affinity suggests long-range allosteric effects within the IgG. Our results provide useful information for developing new therapeutics against HIV-1 and in a broader scope contribute to a better understanding of Ag-Ab recognition.
  • Posted in Journal of Biological Chemistry, Publications
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