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

Mol Immunol. 1998 Jun;35(8):435-43. doi: 10.1016/s0161-5890(98)00057-1.

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 neutralising 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 favourably 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigen-Antibody Reactions / genetics
  • Bacteriophages / chemistry
  • Bacteriophages / genetics
  • Binding Sites / physiology
  • Epitopes / biosynthesis
  • Epitopes / chemistry
  • Epitopes / immunology*
  • Hemagglutinins, Viral / immunology*
  • Measles virus / chemistry*
  • Mice
  • Molecular Mimicry / genetics
  • Peptide Library*
  • Protein Structure, Secondary
  • Sequence Homology, Amino Acid

Substances

  • Epitopes
  • Hemagglutinins, Viral
  • Peptide Library