Molecular analysis of peptides from the GH loop of foot-and-mouth disease virus C-S30 using surface plasmon resonance: a role for kinetic rate constants.
A foot-and-mouth disease virus (FMDV) field variant, isolate C-S30 (also named C(1)-Barcelona), is known to contain four changes within the main antigenic site A (GH loop of capsid protein VP1, residues 136-150), at least one of which (Leu147-->Val) involves a highly conserved position, critical for antibody recognition in the reference strain C-S8c1. However, immunoenzymatic analysis of FMDV C-S30 showed it was recognised by 4C4, a monoclonal antibody that specifically targets site A. This remarkable behaviour has led us to analyse the individual and combined contributions of the four mutations to the antigenicity of C-S30, by surface plasmon resonance (SPR) and enzyme-linked immunosorbent assay (ELISA) studies of pentadecapeptides displaying all possible combinations of the four replacements. Analysis of this family of C-S30-derived analogues shows a certain level of antibody recognition by SPR. In addition, SPR data suggest that kinetic rate constants provide an indirect measure, on the one hand, of paratope accessibility (association rate constant) and, on the other hand, of peptide fitness to the same paratope (dissociation rate constant).
Gomes
P
P
Department of Organic Chemistry, University of Barcelona, Martí i Franquès 1, E-08028, Barcelona, Spain.
Giralt
E
E
Andreu
D
D
D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral / Q000276:immunology*; D005537:Aphthovirus / Q000235:genetics / Q000276:immunology*; D002213:Capsid / Q000235:genetics / Q000276:immunology*; D036022:Capsid Proteins; D003429:Cross Reactions; D000939:Epitopes; D014644:Genetic Variation; D007700:Kinetics; D008969:Molecular Sequence Data; D010446:Peptide Fragments; D020349:Surface Plasmon Resonance
D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D036022:Capsid Proteins; D000939:Epitopes; D010446:Peptide Fragments; C442501:VP1 protein, Foot-and-mouth disease virus