Document Detail


Computational prediction of the cross-reactive neutralizing epitope corresponding to the [corrected] monclonal [corrected] antibody b12 specific for HIV-1 gp120.
MedLine Citation:
PMID:  16940148     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Erez M Bublil; Sharon Yeger-Azuz; Jonathan M Gershoni
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  FASEB journal : official publication of the Federation of American Societies for Experimental Biology     Volume:  20     ISSN:  1530-6860     ISO Abbreviation:  FASEB J.     Publication Date:  2006 Sep 
Date Detail:
Created Date:  2006-08-30     Completed Date:  2006-09-18     Revised Date:  2012-02-15    
Medline Journal Info:
Nlm Unique ID:  8804484     Medline TA:  FASEB J     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1762-74     Citation Subset:  IM    
Affiliation:
Department of Cell Research and Immunology, Tel Aviv University, Ramat Aviv, Aviv 69978, Israel.
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MeSH Terms
Descriptor/Qualifier:
Algorithms
Antibodies, Monoclonal / immunology*
Antigens, CD4 / immunology
Binding Sites, Antibody
Computational Biology / methods
Cross Reactions
DNA / genetics
DNA Primers
Enzyme-Linked Immunosorbent Assay
Epitopes / immunology
HIV Envelope Protein gp120 / immunology*
Humans
Mutagenesis, Site-Directed
Chemical
Reg. No./Substance:
0/Antibodies, Monoclonal; 0/Antigens, CD4; 0/DNA Primers; 0/Epitopes; 0/HIV Envelope Protein gp120; 9007-49-2/DNA
Comments/Corrections
Erratum In:
FASEB J. 2006 Nov;20(13):2426

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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