Antigenicity modulation upon peptide cyclization: application to the GH loop of foot-and-mouth disease virus strain C1-Barcelona.
Foot-and-mouth disease virus (FMDV) isolate C(1)-Barcelona (or C-S30) includes four replacements within its immunodominant site (GH loop, residues 136-150 of capsid protein VP1, YTTSTRGDLAHVTAT), relative to reference strain C-S8c1 (YTASARGDLAHLTTT). Although one of the mutations in C-S30 (147Leu-->Val) is known to be detrimental for antibody recognition, reactivity of this isolate with the neutralizing monoclonal antibody (mAb) 4C4, raised against FMDV C1-Brescia (GH loop: YTASTRGDLAHLTAT), was indistinguishable from those of strains C-S8c1 or C1-Brescia. A structural interpretation for these somewhat striking findings is available, based on the observation that 15-residue peptides reproducing the C-S30 and C-S8c1 GH loops adopt very similar, quasi-circular, conformations in crystal complexes with 4C4. Nevertheless, surface plasmon resonance (SPR) kinetic analyses of the interactions between these peptides and three anti-GH loop mAbs have now revealed that the linear C-S30 peptides were less antigenic in solution than their C-S8c1 and C1-Brescia counterparts. We have, therefore, tried to modulate peptide antigenicity in solution by cyclization. Functional SPR and structural two dimensional proton nuclear magnetic resonance (2D-1H NMR) studies of both linear and cyclic peptide antigens are discussed here. Conformation seems to have an important role in peptide antigenicity, even when continuous (i.e. linear) antigenic sites are involved.
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; D000818:Animals; D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D000956:Antigens, Viral / Q000737:chemistry* / Q000235:genetics; D005537:Aphthovirus / Q000235:genetics / Q000276:immunology*; D002213:Capsid / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D036022:Capsid Proteins; D016056:Immunodominant Epitopes / Q000737:chemistry / Q000235:genetics; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D010456:Peptides, Cyclic / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D020349:Surface Plasmon Resonance; D014614:Vaccines, Synthetic / Q000737:chemistry; D014765:Viral Vaccines / Q000737:chemistry
D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D000956:Antigens, Viral; D036022:Capsid Proteins; D016056:Immunodominant Epitopes; D010446:Peptide Fragments; D010456:Peptides, Cyclic; C442501:VP1 protein, Foot-and-mouth disease virus; D014614:Vaccines, Synthetic; D014765:Viral Vaccines