title: Induction of a cross-reactive CD8(+) T cell response following foot-and-mouth disease virus vaccination.
abstract: Foot-and-mouth disease virus (FMDV) causes a highly contagious infection in cloven-hoofed animals. Current inactivated FMDV vaccines generate short-term, serotype-specific protection, mainly through neutralizing antibody. An improved understanding of the mechanisms of protective immunity would aid design of more effective vaccines. We have previously reported the presence of virus-specific CD8(+) T cells in FMDV-vaccinated and -infected cattle. In the current study, we aimed to identify CD8(+) T cell epitopes in FMDV recognized by cattle vaccinated with inactivated FMDV serotype O. Analysis of gamma interferon (IFN-γ)-producing CD8(+) T cells responding to stimulation with FMDV-derived peptides revealed one putative CD8(+) T cell epitope present within the structural protein P1D, comprising residues 795 to 803 of FMDV serotype O UKG/2001. The restricting major histocompatibility complex (MHC) class I allele was N*02201, expressed by the A31 haplotype. This epitope induced IFN-γ release, proliferation, and target cell killing by αβ CD8(+) T cells, but not CD4(+) T cells. A protein alignment of representative samples from each of the 7 FMDV serotypes showed that the putative epitope is highly conserved. CD8(+) T cells from FMDV serotype O-vaccinated A31(+) cattle recognized antigen-presenting cells (APCs) loaded with peptides derived from all 7 FMDV serotypes, suggesting that CD8(+) T cells recognizing the defined epitope are cross-reactive to equivalent peptides derived from all of the other FMDV serotypes.
authors.affiliation: Institute for Animal Health, Compton, Newbury, United Kingdom. efrain.guzman@bbsrc.ac.uk
authors.forename: Efrain
authors.initials: E
authors.lastname: Guzman
authors.forename: Geraldine
authors.initials: G
authors.lastname: Taylor
authors.forename: Bryan
authors.initials: B
authors.lastname: Charleston
authors.forename: Shirley A
authors.initials: SA
authors.lastname: Ellis
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D036022:Capsid Proteins / Q000235:genetics; D002417:Cattle; D002418:Cattle Diseases / Q000276:immunology / Q000517:prevention & control*; D003429:Cross Reactions; D058501:Enzyme-Linked Immunospot Assay; D018984:Epitopes, T-Lymphocyte / Q000235:genetics* / Q000378:metabolism; D005434:Flow Cytometry; D005536:Foot-and-Mouth Disease / Q000276:immunology / Q000517:prevention & control*; D029544:Foot-and-Mouth Disease Virus / Q000235:genetics / Q000276:immunology*; D007371:Interferon-gamma / Q000276:immunology; D014611:Vaccination / Q000662:veterinary*
chemical_list: D036022:Capsid Proteins; D018984:Epitopes, T-Lymphocyte; D007371:Interferon-gamma