TY - JOUR
T1 - Enhanced antigenicity of a four-contact-residue epitope of the measles virus hemagglutinin protein by phage display libraries
T2 - Evidence of a helical structure in the putative active site
AU - Deroo, Sabrina
AU - El Kasmi, Karim C.
AU - Fournier, Philippe
AU - Theisen, Dietmar
AU - Brons, Nicolaas H.C.
AU - Herrmann, Markus
AU - Desmet, Johan
AU - Muller, Claude P.
PY - 1998/5/1
Y1 - 1998/5/1
N2 - 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.
AB - 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.
KW - Helix structure
KW - Hemagglutinin protein
KW - Linear epitope
KW - Measles virus
KW - Neutralizing antibodies
KW - Peptide
UR - http://www.scopus.com/inward/record.url?scp=0031695082&partnerID=8YFLogxK
U2 - 10.1016/S0161-5890(98)00057-1
DO - 10.1016/S0161-5890(98)00057-1
M3 - Article
C2 - 9798648
AN - SCOPUS:0031695082
SN - 0161-5890
VL - 35
SP - 435
EP - 443
JO - Molecular Immunology
JF - Molecular Immunology
IS - 8
ER -