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Journal of Virology, May 2000, p. 4902-4907, Vol. 74, No. 10
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Interspecies Major Histocompatibility Complex-Restricted Th Cell Epitope on Foot-and-Mouth Disease Virus Capsid Protein VP4

Esther Blanco,1 Kenneth McCullough,2,* Artur Summerfield,2 Jude Fiorini,2 David Andreu,3 Cristina Chiva,3 Eva Borrás,3 Paul Barnett,4 and Francisco Sobrino1,5

Centro de Investigation en Sanidad Animal, INIA, Valdeolmos, 28130 Madrid,1 Departament de Química Orgànica, Universitat de Barcelona, 08028 Barcelona,3 and Centro de Biología Molecular "Severo Ochoa" (CSIC-UAM), Cantoblanco, 28049 Madrid,5 Spain; Institute of Virology and Immunoprophylaxis, Mittelhäusern, Switzerland2; and BBSRC Institute for Animal Health, Pirbright, Surrey GU24 ONF, England4

Received 13 October 1999/Accepted 16 February 2000

T-cell epitopes within viral polypeptide VP4 of the capsid protein of foot-and-mouth disease virus were analyzed using 15-mer peptides and peripheral blood mononuclear cells (PBMC) from vaccinated outbred pigs. An immunodominant region between VP4 residues 16 and 35 was identified, with peptide residues 20 to 34 (VP4-0) and 21 to 35 (VP4-5) particularly immunostimulatory for PBMC from all of the vaccinated pigs. CD25 upregulation on peptide-stimulated CD4+ CD8+ cells---dominated by Th memory cells in the pig---and inhibition using anti-major histocompatibility complex class II monoclonal antibodies indicated recognition by Th lymphocytes. VP4-0 immunogenicity was retained in a tandem peptide with the VP1 residue 137 to 156 sequential B-cell epitope. This B-cell site also retained immunogenicity, but evidence is presented that specific antibody induction in vitro required both this and the T-cell site. Heterotypic recognition of the residue 20 to 35 region was also noted. Consequently, the VP4 residue 20 to 35 region is a promiscuous, immunodominant and heterotypic T-cell antigenic site for pigs that is capable of providing help for a B-cell epitope when in tandem, thus extending the possible immunogenic repertoire of peptide vaccines.


* Corresponding author. Mailing address: Institute of Virology and Immunoprophylaxis, Sensemattstrasse 293, 3147 Mittelhäusern, Switzerland. Phone: 41-31-8489361. Fax: 41-31-8489222. E-mail: kenneth.mccullough{at}ivi.admin.ch.


Journal of Virology, May 2000, p. 4902-4907, Vol. 74, No. 10
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.



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