title: 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.
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.
authors.affiliation: Laboratoire National de Santé, Luxembourg, Luxembourg.
authors.forename: S
authors.initials: S
authors.lastname: Deroo
authors.forename: K C
authors.initials: KC
authors.lastname: El Kasmi
authors.forename: P
authors.initials: P
authors.lastname: Fournier
authors.forename: D
authors.initials: D
authors.lastname: Theisen
authors.forename: N H
authors.initials: NH
authors.lastname: Brons
authors.forename: M
authors.initials: M
authors.lastname: Herrmann
authors.forename: J
authors.initials: J
authors.lastname: Desmet
authors.forename: C P
authors.initials: CP
authors.lastname: Muller
mesh_terms: D000818:Animals; D000937:Antigen-Antibody Reactions / Q000235:genetics; D001435:Bacteriophages / Q000737:chemistry / Q000235:genetics; D001665:Binding Sites / Q000502:physiology; D000939:Epitopes / Q000096:biosynthesis / Q000737:chemistry / Q000276:immunology*; D006389:Hemagglutinins, Viral / Q000276:immunology*; D008459:Measles virus / Q000737:chemistry*; D051379:Mice; D018716:Molecular Mimicry / Q000235:genetics; D019151:Peptide Library; D017433:Protein Structure, Secondary; D017386:Sequence Homology, Amino Acid
chemical_list: D000939:Epitopes; D006389:Hemagglutinins, Viral; D019151:Peptide Library