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Abstract

BackgroundImmunity 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.ResultsOf 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-γ 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.ConclusionThe 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.

Genetic Diversity and Sequence Polymorphism of Two Genes Encoding Theileria parva Antigens Recognized by CD8+ T Cells among Vaccinated and Unvaccinated Cattle in Malawi

“…Thus, the Tp1 and Tp2 genes are good genetic markers to evaluate the impact of the vaccination. These can also be used to characterize the strains of T. parva and to study the nature and selection forces affecting the diversity in these antigens that stimulate T cell responses in cattle [25][26][27][28].…”

Genes encoding two Theileria parva antigens recognized by CD8+ T-cells exhibit sequence diversity in South Sudanese cattle populations but the majority of alleles are similar to the Muguga component of the live vaccine cocktail

“…parva antigens and epitopes recognized by CD8 + T-cells from T . parva –immune cattle [ 12 – 15 ] provides an opportunity to address the nature and selective pressures driving diversity in antigens that induce T cell responses in cattle. Detailed study of immune responses to two of these antigens, Tp1 andTp2, demonstrated that they represent immunodominant target antigens recognised by CD8 + T-cell responses in cattle with specific class I MHC haplotypes [ 16 ].…”

Expression Analysis of the Theileria parva Subtelomere-Encoded Variable Secreted Protein Gene Family

“…The elimination of T. parva -infected lymphocytes by MHC class I-restricted cytotoxic T cell responses is a proven effector mechanism for protective immunity in cattle [18], [19]. Therefore such proteins could also function as vaccine antigens and there is preliminary evidence to support this [20], [21].…”