A similar pattern of interaction for different antibodies with a major antigenic site of foot-and-mouth disease virus: implications for intratypic antigenic variation.
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.
Verdaguer
N
N
Centre de Investigació i Desenvolupament (CSIC), Barcelona, Spain.
Sevilla
N
N
Valero
M L
ML
Stuart
D
D
Brocchi
E
E
Andreu
D
D
Giralt
E
E
Domingo
E
E
Mateu
M G
MG
Fita
I
I
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
D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D000936:Antigen-Antibody Complex; D000956:Antigens, Viral; D007140:Immunoglobulin Fab Fragments