Immunodominance, clonal composition and TCRß repertoire of the bovine CD8⁺ T-cell response to Theileria parva

Abstract

In view of the evidence that CD8+ T-cells are involved in mediating immunity against Theileria parva, the antigens recognised by these cells are obvious candidates for inclusion in a subunit vaccine. Results from previous studies have inferred that the CD8+ T-cell response to T. parva is focused on a limited number of immunodominant antigens that exhibit polymorphism between different parasite strains. This could pose a major challenge to the design of a broadly effective subunit vaccine. The recent identification of CTL target antigens has provided the opportunity to characterise immunodominance within the T. parva systemThe objective of this study was to quantitatively assess immunodominance in the CD8+ T-cell response to T. parva and to characterise the clonal composition and TCRp repertoires ofthe epitope-specific T-cell populations. The results from four animals presented in this study have demonstrated that the CDS T-cell response restricted by two MHC class I haplotypes is reproducibly dominated by single polymorphic epitopes. Using a suite of molecular tools developed during this study it was determined that the T-cell populations specific for both these epitopes were polyclonal but dominated by a limited number of large clonal expansions and the TCRP repertoires expressed by these populations was diverse.During the course of this work several novel bovine TCRp genes were identified. Further examination ofTCRp cDNA transcripts and the bovine genome assembly substantially expanded the known bovine TCRP repertoire, which is now the largest characterised for any species. Notably several VP subfamilies, especially Vpi and 13 have undergone extensive duplication and contain large numbers of genes. By annotating the available genomic data it has been shown that the bovine TCRB locus has a highly conserved synteny with the human TCRB locus. Furthermore, this annotation has demonstrated that prodigious duplication of a cassette containing a Vpi and Vpi3 gene has contributed to the large membership of these two subfamilies and that there are three D-J-Cp clusters in the bovine TCRB locus rather than the two seen in the other mammalian TCRB loci described

    Similar works