title: Transcending the structuralist paradigm in immunology-affinity and biological activity rather than purely structural considerations should guide the design of synthetic peptide epitopes.
abstract: Synthetic peptides are frequently used to mimic the antigenic sites of proteins. In order to increase the level of mimicry between the peptide and the protein, it is important to understand the structural basis of protein antigenicity. A review of recent crystal structures of antigen-antibody complexes shows that important conformational rearrangements occur in both antigen and antibody during complexation and that many water molecules are located at the complex interface. Both these features are responsible for the low success rate of antigen-antibody docking. The complementarity observed in the complex cannot be predicted from the structure of the free molecules before the occurrence of induced fit and mutual adaptation. The structuralist paradigm assumes that it is possible to understand complex biological recognition phenomena solely in terms of structural data. However, the dynamic component of protein structure requires that both space and time dimensions be included in the description of antigenic specificity. This means that both structural data and activity measurements are required for understanding immunological interactions and for designing synthetic epitopes. The recently developed biosensor technology should greatly facilitate the quantitative measurement of binding interactions and the design of synthetic peptide epitopes.
authors.affiliation: Centre National de la Recherche Scientifique (CNRS), Institut de Biologie Moléculaire et Cellulaire, Strasbourg, France.
authors.forename: M H
authors.initials: MH
authors.lastname: Van Regenmortel
mesh_terms: D000937:Antigen-Antibody Reactions; D000939:Epitopes / Q000737:chemistry* / Q000276:immunology; D018716:Molecular Mimicry / Q000276:immunology*; D010455:Peptides / Q000737:chemistry* / Q000276:immunology; D013329:Structure-Activity Relationship
chemical_list: D000939:Epitopes; D010455:Peptides