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Computational prediction of the cross-reactive neutralizing epitope corresponding to the monoclonal antibody b12 specific for HIV-1 gp120

Department of Cell Research and Immunology, Tel-Aviv University, Tel-Aviv, Israel

¹Correspondence: Department of Cell Research and Immunology, Tel Aviv University, Ramat Aviv, Aviv 69978, Israel. E-mail: gershoni{at}tauex.tau.ac.il

Backtracking from antibodies to their corresponding epitopes is a rational approach for vaccine design. Here we apply such a reverse immunological strategy for mapping the cross-reactive neutralizing epitope corresponding to the monoclonal antibody (mAb) b12 specific for HIV-1 gp120. b12 was used to screen a combinatorial phage display random peptide library and nineteen 12mer cysteine-looped peptides were affinity purified. These were used as input for analysis with the predictive algorithm Mapitope. Based on the input panel of peptides and the antigen’s atomic structure, Mapitope predicts candidate epitopes on the surface of the antigen. Two major clusters were predicted as candidate b12 epitopes. These could be discriminated by a series of experiments, which included point mutagenesis of selected residues and binding assays. Moreover, the prediction of the b12 epitope was further strengthened by comparison with additional predictions for two competing antibodies, b6 and m14. Finally, support of our prediction was obtained in view of the fact that b12, m14, and b6 were found to compete against mAb 17b binding to gp120. The b12 epitope is predicted to consist of four peptide segments of gp120 (residues V254-T257, D368-F376, E381-Y384, and I420-I424), which lie at the periphery of the CD4 binding site.—Bublil, E. M., Yeger-Azuz, S., Gershoni, J. M. Computational prediction of the cross-reactive neutralizing epitope corresponding to monoclonal antibody b12 specific for HIV-1 gp120.

Key Words: Mapitope algorithm • combinatorial phage display peptide library • epitope mapping • vaccine design

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