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A novel strategy for the identification of antigens that are recognised by bovine MHC class I restricted cytotoxic T cells in a protozoan infection using reverse vaccinology.

Graham, SP, Honda, Y, Pellé, R, Mwangi, DM, Glew, EJ, de Villiers, EP, Shah, T, Bishop, R, van der Bruggen, P, Nene, V and Taracha, EL (2007) A novel strategy for the identification of antigens that are recognised by bovine MHC class I restricted cytotoxic T cells in a protozoan infection using reverse vaccinology. Immunome Res, 3.

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Abstract

BACKGROUND: Immunity against the bovine protozoan parasite Theileria parva has previously been shown to be mediated through lysis of parasite-infected cells by MHC class I restricted CD8+ cytotoxic T lymphocytes. It is hypothesized that identification of CTL target schizont antigens will aid the development of a sub-unit vaccine. We exploited the availability of the complete genome sequence data and bioinformatics tools to identify genes encoding secreted or membrane anchored proteins that may be processed and presented by the MHC class I molecules of infected cells to CTL. RESULTS: Of the 986 predicted open reading frames (ORFs) encoded by chromosome 1 of the T. parva genome, 55 were selected based on the presence of a signal peptide and/or a transmembrane helix domain. Thirty six selected ORFs were successfully cloned into a eukaryotic expression vector, transiently transfected into immortalized bovine skin fibroblasts and screened in vitro using T. parva-specific CTL. Recognition of gene products by CTL was assessed using an IFN-gamma ELISpot assay. A 525 base pair ORF encoding a 174 amino acid protein, designated Tp2, was identified by T. parva-specific CTL from 4 animals. These CTL recognized and lysed Tp2 transfected skin fibroblasts and recognized 4 distinct epitopes. Significantly, Tp2 specific CD8+ T cell responses were observed during the protective immune response against sporozoite challenge. CONCLUSION: The identification of an antigen containing multiple CTL epitopes and its apparent immunodominance during a protective anti-parasite response makes Tp2 an attractive candidate for evaluation of its vaccine potential.

Item Type: Article
Subjects : Veterinary Medicine
Divisions : Faculty of Health and Medical Sciences > School of Veterinary Medicine
Authors :
AuthorsEmailORCID
Graham, SPUNSPECIFIEDUNSPECIFIED
Honda, YUNSPECIFIEDUNSPECIFIED
Pellé, RUNSPECIFIEDUNSPECIFIED
Mwangi, DMUNSPECIFIEDUNSPECIFIED
Glew, EJUNSPECIFIEDUNSPECIFIED
de Villiers, EPUNSPECIFIEDUNSPECIFIED
Shah, TUNSPECIFIEDUNSPECIFIED
Bishop, RUNSPECIFIEDUNSPECIFIED
van der Bruggen, PUNSPECIFIEDUNSPECIFIED
Nene, VUNSPECIFIEDUNSPECIFIED
Taracha, ELUNSPECIFIEDUNSPECIFIED
Date : 2007
Identification Number : 10.1186/1745-7580-3-2
Copyright Disclaimer : © 2007 Graham et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Related URLs :
Additional Information : © 2007 Graham et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Depositing User : Symplectic Elements
Date Deposited : 22 Mar 2016 15:43
Last Modified : 24 Mar 2016 09:35
URI: http://epubs.surrey.ac.uk/id/eprint/810174

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