The mapping and reconstitution of a conformational discontinuous B-cell epitope of HIV-1

David Enshell-Seijffers, Dmitri Denisov, Bella Groisman, Larisa Smelyanski, Ronit Meyuhas, Gideon Gross, Galina Denisova, Jonathan M. Gershoni

Research output: Contribution to journalArticlepeer-review

86 Scopus citations

Abstract

A method for the discovery of the structure of conformational discontinuous epitopes of monoclonal antibodies (mAbs) is described. The mAb is used to select specific phages from combinatorial phage-display peptide libraries that in turn are used as an epitope-defining database that is applied via a novel computer algorithm to analyze the crystalline structure of the original antigen. The algorithm is based on the following: (1) Most contacts between a mAb and an antigen are through side-chain atoms of the residues. (2) In the three-dimensional structure of a protein, amino acid residues remote in linear sequence can juxtapose to one another through folding. (3) Tandem amino acid residues of the selected phage-displayed peptides can represent pairs of juxtaposed amino acid residues of the antigen. (4) Contact residues of the epitope are accessible to the antigen surface. (5) The most frequent tandem pairs of amino acid residues in the selected phage-displayed peptides can reflect pairs of juxtaposed amino acid residues of the epitope. Application of the algorithm enabled prediction of epitopes. On the basis of these predictions, segments of an antigen were used to reconstitute an antigenic epitope mimetic that was recognized by its original mAb.

Original languageEnglish
Pages (from-to)87-101
Number of pages15
JournalJournal of Molecular Biology
Volume334
Issue number1
DOIs
StatePublished - 14 Nov 2003
Externally publishedYes

Bibliographical note

Funding Information:
The authors thank Professor James Robinson for providing us with 17b mAb and Dr François Mallet for providing 13b5 mAb. This research was supported by The Israel Science Foundation. The authors are grateful to Dr Edward Spigelman for useful discussions and consultation.

Funding

The authors thank Professor James Robinson for providing us with 17b mAb and Dr François Mallet for providing 13b5 mAb. This research was supported by The Israel Science Foundation. The authors are grateful to Dr Edward Spigelman for useful discussions and consultation.

FundersFunder number
Israel Science Foundation

    Keywords

    • Computer algorithm
    • Epitope
    • Monoclonal antibody
    • Phage display
    • Protein conformation

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