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

• Type: Article in International Scientific Journal
• Date: 2001

Authors

Gomes, P (Author) FCUP; Giralt, E (Author) Other; Andreu, D (Author) Other

Journal

Title: Vaccine

Vol. 19

Pages: 3459-3466

ISSN: 0264-410X

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 10 Citations

Scopus - 10 Citations

Scientific classification

FOS: Medical and Health sciences > Basic medicine

Other information

Authenticus ID: P-007-9ZQ

DOI: 10.1016/s0264-410x(01)00047-0

Abstract (EN): 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-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 against FMDV C-1-Brescia (GH loop: YTASTRGDLAHLTAT), was indistinguishable from those of strains C-S8cl or C-1-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-S8cl 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-S8cl and C-1-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-H-1 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.

Language: English

Type (Professor's evaluation): Scientific