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Title: Immunodominance, clonal composition and TCRβ repertoire of the bovine CD8+ T-cell response to Theileria parva
Author: Connelley, T.
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2007
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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 object of this study was to quantitatively assess immunodominance in the CD8+ T-cell response to T. parva and to characterise the clonal composition and TCRβ repertoires of the epitope-specific T-cell populations. The results from four animals presented in this study have demonstrated that the CD8+ T-cell response restricted by two MHC class I haplotypes is reproducibly dominated by single polymorphic epitopes. The T-cell populations specific for both these epitopes were polyclonal but dominated by a limited number of large clonal expansions and the TCRβ repertoires expressed by these populations were diverse. During the course of this work several novel bovine TCRβ genes were identified. Further examination of TCRβ cDNA transcripts and the bovine genome assembly substantially expanded the known bovine TCRβ repertoire, which is now the largest characterised for any species. Notably several Vβ subfamilies, especially Vβ1 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 TCRβ locus has a highly conserved synteny with the human TCRβ locus. Furthermore this annotation has demonstrated that prodigious duplication of a cassette containing a Vβ1 and Vβ13 gene has contributed to the large membership of these two subfamilies and that there are three D-J-Cβ clusters in the bovine TCRB locus rather than in the two seen in the other mammalian TCRβ loci described.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available