Antigenicity modulation upon peptide cyclization: application to the GH loop of foot-and-mouth disease virus strain C-1-Barcelona

Foot-and-mouth disease virus (FMDV) isolate C-1-Barcelona (or C-S30) includ es four replacements within its immunodominant site (GH loop, residues 136- 150 of capsid protein VP1, YTTSTRGDLAHVTAT), relative to reference strain C -S8cl (YTASAR-GDLAHLTTT). Although one of the mutations in C-S30 ((147)Leu --> Val) is known to be detrimental for antibody recognition, reactivity of this isolate with the neutralizing monoclonal antibody (mAb) 4C4, raised a gainst FMDV C-1-Brescia (GH loop: YTASTRGDLAHLTAT), was indistinguishable f rom those of strains C-S8cl or C-1-Brescia. A structural interpretation for these somewhat striking findings is available, based on the observation th at 15-residue peptides reproducing the C-S30 and C-S8cl GH loops adopt very similar, quasi-circular, conformations in crystal complexes with 4C4. Neve rtheless, surface plasmon resonance (SPR) kinetic analyses of the interacti ons between these peptides and three anti-GH loop mAbs have now revealed th at the linear C-S30 peptides were less antigenic in solution than their C-S 8cl and C-1-Brescia counterparts. We have, therefore, tried to modulate pep tide antigenicity in solution by cyclization. Functional SPR and structural two dimensional proton nuclear magnetic resonance (2D-H-1 NMR) studies of both linear and cyclic peptide antigens are discussed here. Conformation se ems to have an important role in peptide antigenicity, even when continuous (i.e. linear) antigenic sites are involved. (C) 2001 Elsevier Science Ltd. All rights reserved.