Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.487214
Title: Transcriptional changes accompanying CD8 cross-linking: implications for CTL antiviral activity and co-receptor function
Author: Abidi, Saiyed Hussain Imam
Awarding Body: University of Oxford
Current Institution: University of Oxford
Date of Award: 2007
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Abstract:
Atag-based transcriptome analysis technology, called serial analysis of gene expression or 'SAGE', was used to characterize the transcriptional remodeling accompanying T cell activation and the anti-CDS antibody treatment of a well-characterized human .cytotoxic CDS+ T cell clone. Our results emphasize the remarkable transcriptional plasticity of T cells. A large number of genes are up regulated in the activated T cell; however, even more are down regulated, implying that transcriptional silencing has a major role in T cell activation. Unexpectedly, the molecular functions of a large fraction of highly T cell-specific transcripts in the activated T cells are uncharacterized. Nevertheless, only one percent of the SAGE tags matching novel regions of the genome are likely to correspond to novel structural genes. A much larger proportion of the tags correspond instead to the 3' UTRs of known genes. Among the highly T-cell specific transcripts only four encode new cell surface proteins, suggesting that our understanding of the composition of the activated T cell surface, like that of resting T cells, is now largely complete. The transcriptional response to anti-CDS antibody crosslinking is comparable in scale to that induced by anti-CD3 antibody treatment, but is characterized by the up-regulation of inhibitory genes. Among these, the casein kinase and SHP-I phosphatase genes were also induced by antagonist but not agonist ligands in an antagonized cytotoxic T cell clone, suggesting that similar inhibitory expression patterns may be the underlying feature of T cell antagonism, confounding the 'competition' model of T cell antagonsim. Finally, using SAGE we characterized a putative anti-viral activity induced by anti-CDS antibody treatment of cytotoxic T cell clones. None of the known anti-HIV factors contribute to this activity, suggesting the existence of unidentified anti-viral factor(s).
Supervisor: Not available Sponsor: Not available
Qualification Name: University of Oxford, 2007 Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.487214  DOI: Not available
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