Interspecies major histocompatibility complex-restricted Th cell epitope on foot-and-mouth disease virus capsid protein VP4

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 immunodomin ant region between VP4 residues 16 and 35 was identified, with peptide resi dues 20 to 34 (VP4-0) and 21 to 35 (VP4-5) particularly immunostimulatory f or PBMC from all of the vaccinated pigs. CD25 upregulation on peptide-stimu lated CD4(+) CD8(+) cells-dominated by Th memory cells in the pig-and inhib ition using anti-major histocompatibility complex class II monoclonal antib odies indicated recognition by Th lymphocytes. VP4-0 immunogenicity was ret ained 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 pr esented that specific antibody induction in vitro required both this and th e T-cell site. Heterotypic recognition of the residue 20 to 35 region was a lso noted. Consequently, the VP4 residue 20 to 35 region is a promiscuous, immunodominant and heterotypic T-cell antigenic site for pigs that is capab le of providing help for a B-cell epitope when in tandem, thus extending th e possible immunogenic repertoire of peptide vaccines.