Enhanced antigenicity of a four-contact-residue epitope of the measles virus hemagglutinin protein by phage display libraries: Evidence of a helical structure in the putative active site

Sabrina Deroo, Karim C. El Kasmi, Philippe Fournier, Dietmar Theisen*, Nicolaas H.C. Brons, Markus Herrmann, Johan Desmet, Claude P. Muller

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

23 Citations (Scopus)

Abstract

Antigenicity and conformational propensities of synthetic peptides corresponding to the sequential epitope H236-255 of the measles virus hemagglutinin protein were investigated. This epitope corresponds to the neutralizing and protective monoclonal antibody BH129 and includes Arg243, implicated in CD46-down-regulation and Arg253 that has been mapped to the putative enzymatic site. Fine mapping with truncation-, elongation-, Gly- and Ala-substitution analogues defined EL-QL as the critical residues of the minimal epitope S244ELSQL249. CD spectra of peptides, comparison with the 3D-structure of homologous sequences, and prediction algorithms suggested a helical structure with the contact residues E245L-QL249 located on the protein surface. Mimotopes obtained with a 6-mer phage display library contained a consensus Pro (important for binding) instead of Ser247 of the wild-type sequence (irrelevant for binding). The kink induced by Pro seemed to be essential to bring the 4 contact-residues in the mimotopes and in the corresponding short peptides together. CD analysis and prediction algorithms suggested that non-helical conformations of the phage insert and of the peptides may favorably mimic the antigenic helical turns of the wild-type sequence, resulting in an up to 135 times higher antigenicity of the mAb towards the mimotope peptides.

Original languageEnglish
Pages (from-to)435-443
Number of pages9
JournalMolecular Immunology
Volume35
Issue number8
DOIs
Publication statusPublished - 1 May 1998
Externally publishedYes

Keywords

  • Helix structure
  • Hemagglutinin protein
  • Linear epitope
  • Measles virus
  • Neutralizing antibodies
  • Peptide

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