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Proteome-Wide Screening Reveals Immunodominance in the CD8 T Cell Response against Classical Swine Fever Virus with Antigen-Specificity Dependent on MHC Class I Haplotype Expression

Franzoni, G, Kurkure, NV, Essler, SE, Pedrera, M, Everett, HE, Bodman-Smith, KB, Crooke, HR and Graham, SP (2013) Proteome-Wide Screening Reveals Immunodominance in the CD8 T Cell Response against Classical Swine Fever Virus with Antigen-Specificity Dependent on MHC Class I Haplotype Expression PLOS ONE, 8 (12), ARTN e8424.

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Abstract

Vaccination with live attenuated classical swine fever virus (CSFV) vaccines induces a rapid onset of protection which has been associated with virus-specific CD8 T cell IFN-γ responses. In this study, we assessed the specificity of this response, by screening a peptide library spanning the CSFV C-strain vaccine polyprotein to identify and characterise CD8 T cell epitopes. Synthetic peptides were pooled to represent each of the 12 CSFV proteins and used to stimulate PBMC from four pigs rendered immune to CSFV by C-strain vaccination and subsequently challenged with the virulent Brescia strain. Significant IFN-γ expression by CD8 T cells, assessed by flow cytometry, was induced by peptide pools representing the core, E2, NS2, NS3 and NS5A proteins. Dissection of these antigenic peptide pools indicated that, in each instance, a single discrete antigenic peptide or pair of overlapping peptides was responsible for the IFN-γ induction. Screening and titration of antigenic peptides or truncated derivatives identified the following antigenic regions: core241–255 PESRKKLEKALLAWA and NS31902–1912 VEYSFIFLDEY, or minimal length antigenic peptides: E2996–1003 YEPRDSYF, NS21223–1230 STVTGIFL and NS5A3070–3078 RVDNALLKF. The epitopes are highly conserved across CSFV strains and variable sequence divergence was observed with related pestiviruses. Characterisation of epitope-specific CD8 T cells revealed evidence of cytotoxicity, as determined by CD107a mobilisation, and a significant proportion expressed TNF-α in addition to IFN-γ. Finally, the variability in the antigen-specificity of these immunodominant CD8 T cell responses was confirmed to be associated with expression of distinct MHC class I haplotypes. Moreover, recognition of NS21223–1230 STVTGIFL and NS31902–1912 VEYSFIFLDEY by a larger group of C-strain vaccinated animals showed that these peptides could be restricted by additional haplotypes. Thus the antigenic regions and epitopes identified represent attractive targets for evaluation of their vaccine potential against CSFV.

Item Type: Article
Subjects : Veterinary Science
Divisions : Faculty of Health and Medical Sciences > School of Veterinary Medicine
Authors :
AuthorsEmailORCID
Franzoni, GUNSPECIFIEDUNSPECIFIED
Kurkure, NVUNSPECIFIEDUNSPECIFIED
Essler, SEUNSPECIFIEDUNSPECIFIED
Pedrera, MUNSPECIFIEDUNSPECIFIED
Everett, HEUNSPECIFIEDUNSPECIFIED
Bodman-Smith, KBUNSPECIFIEDUNSPECIFIED
Crooke, HRUNSPECIFIEDUNSPECIFIED
Graham, SPUNSPECIFIEDUNSPECIFIED
Date : 23 December 2013
Identification Number : 10.1371/journal.pone.0084246
Copyright Disclaimer : Copyright 2013 Franzoni et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Uncontrolled Keywords : Science & Technology, Multidisciplinary Sciences, Science & Technology - Other Topics, MULTIDISCIPLINARY SCIENCES, ESCAPE MUTATION, DENGUE VIRUS, IDENTIFICATION, PROTECTION, LYMPHOCYTES, EPITOPES, CSFV, VACCINATION, PROTEINS, VACCINES
Related URLs :
Additional Information : Copyright 2013 Franzoni et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Depositing User : Symplectic Elements
Date Deposited : 22 Mar 2016 11:42
Last Modified : 24 Mar 2016 09:25
URI: http://epubs.surrey.ac.uk/id/eprint/810180

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