title: A similar pattern of interaction for different antibodies with a major antigenic site of foot-and-mouth disease virus: implications for intratypic antigenic variation.
abstract: The three-dimensional structures of the Fab fragment of a neutralizing antibody raised against a foot-and-mouth disease virus (FMDV) of serotype C1, alone and complexed to an antigenic peptide representing the major antigenic site A (G-H loop of VP1), have been determined. As previously seen in a complex of the same antigen with another antibody which recognizes a different epitope within antigenic site A, the receptor recognition motif Arg-Gly-Asp and some residues from an adjacent helix participate directly in the interaction with the complementarity-determining regions of the antibody. Remarkably, the structures of the two antibodies become more similar upon binding the peptide, and both undergo considerable induced fit to accommodate the peptide with a similar array of interactions. Furthermore, the pattern of reactivities of five additional antibodies with versions of the antigenic peptide bearing amino acid replacements suggests a similar pattern of interaction of antibodies raised against widely different antigens of serotype C. The results reinforce the occurrence of a defined antigenic structure at this mobile, exposed antigenic site and imply that intratypic antigenic variation of FMDV of serotype C is due to subtle structural differences that affect antibody recognition while preserving a functional structure for the receptor binding site.
authors.affiliation: Centre de Investigació i Desenvolupament (CSIC), Barcelona, Spain.
authors.forename: N
authors.initials: N
authors.lastname: Verdaguer
authors.forename: N
authors.initials: N
authors.lastname: Sevilla
authors.forename: M L
authors.initials: ML
authors.lastname: Valero
authors.forename: D
authors.initials: D
authors.lastname: Stuart
authors.forename: E
authors.initials: E
authors.lastname: Brocchi
authors.forename: D
authors.initials: D
authors.lastname: Andreu
authors.forename: E
authors.initials: E
authors.lastname: Giralt
authors.forename: E
authors.initials: E
authors.lastname: Domingo
authors.forename: M G
authors.initials: MG
authors.lastname: Mateu
authors.forename: I
authors.initials: I
authors.lastname: Fita
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral / Q000737:chemistry; D000936:Antigen-Antibody Complex / Q000737:chemistry / Q000235:genetics; D000940:Antigenic Variation; D000956:Antigens, Viral / Q000737:chemistry / Q000235:genetics*; D005537:Aphthovirus / Q000145:classification / Q000235:genetics* / Q000276:immunology*; D001665:Binding Sites / Q000235:genetics; D002417:Cattle; D018360:Crystallography, X-Ray; D007140:Immunoglobulin Fab Fragments / Q000737:chemistry; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D011487:Protein Conformation; D012703:Serotyping
chemical_list: D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D000936:Antigen-Antibody Complex; D000956:Antigens, Viral; D007140:Immunoglobulin Fab Fragments