This article is more than 5 years old. Information may no longer be current.
Research may lead to new therapeutics against HIV-1
Click Here to Manage Email Alerts
In the binding thermodynamics of the broadly neutralizing anti-HIV monoclonal antibody 1 mAb 2F5 to its gp41 epitope, residues adjoining the core epitope, as well as the immunoglobulin Fc area, play significant roles in binding affinity, according to recent findings.
In the study, researchers utilized isothermal titration calorimetry to thermodynamically evaluate the relationships between broadly neutralizing monoclonal antibody (bNAb) 2F5, in both IgG and Fab forms, and its epitope peptides.
The researchers titrated the antibody solutions in the calorimetric cell with the corresponding peptide in concurrent injections at different volumes (range, 5-15 mcL). The analogous heats of peptide dilution into buffer were assessed in separate analyses and utilized to correct the binding heats. The researchers analyzed the isotherms based on a binding model of an independent and identical sites.
The investigators found that, as anticipated, the number of binding sites of the Fab resulting from the fits were close to 1 for both peptides. Additionally, they found the binding enthalpy to be large and negative (−10.3 ± 0.4 kcal/mol-1) and opposed by a negative entropy charge.
The bNAb 2F5 IgG had the highest affinity for its functional epitope, suggesting that additional mechanisms involving residues adjacent to the core epitope play a key role in higher affinity. Moreover, the Fc region exerted a strong influence on binding affinity, indicating long-range allosteric influences within IgG.
According to the researchers, these findings may contribute to the development of new treatments or vaccines for HIV.
“The thermodynamic parameters determined here for the 2F5 bNAb to its cognate epitope and the results related to the implication of the Fc region in the Ab affinity are important understanding the structural and thermodynamic determinants of Ag-Ab recognition and
provide useful information for the design of new therapeutics and vaccines against HIV,” the researchers wrote.
Disclosure: The research was funded by the Seventh Framework Programme of the European Union.
Click Here to Manage Email Alerts