Characterisation of the CD4+ T-cell response against oncogenic human papillomavirus from healthy volunteers

Gallagher, Kathleen 2005. Characterisation of the CD4+ T-cell response against oncogenic human papillomavirus from healthy volunteers. PhD Thesis, Cardiff University.

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Abstract

In this study the principal aim was to investigate the HPV E6 and E7 specific-T-cell responses in healthy women, from which novel T-cell epitopes could be defined and characterised. Ten healthy female donors were screened for T-cell responses against HPV16 and HPV18 E6 and E7 peptide pools. Five donors made HPV E6 specific responses (as detected by IFNgamma ELISpot assay), and 6 CD4+ T-cell epitopes were defined; HPV16 E6(19-33, 85-99, 121-135, 127-141) and HPV18 E6(43-57, 49-63). The four epitopes investigated further were all HLA-DR restricted and peptides HPV16 E6(127-141) and HPV18 E6(43-57) </sub>were shown to be presented by HLA-DRB1*01 and HLA-DRB1*15 respectively. Two T-cell lines were generated from one individual against the HPV16 E6(127-141) epitope. These lines exclusively express either TCR Vbeta16 (Belx1) or TCR Vbeta7 (Belx22), and demonstrate highly differential cytokine secretion profiles in response to peptide re-stimulation. The endogenous processing and presentation of the HPV16 E6(127-141) epitope from a full length recombinant HPV16 E6 protein was demonstrated with a range of different antigen presenting cells and the Belx2 T-cell line. Overall this study demonstrates a powerful approach for defining novel CD4+ T-cell epitopes that may be useful in investigating protective T-cell responses and how HPV oncoproteins are naturally presented to the immune system. The Belx1 and Belx2 T-cell lines are valuable immunological tools that can be used further investigate the HPV16 E6127-141) response. The epitopes defined in this study could potentially be useful in an immunotherapeutic context, either indirectly through their use in monitoring vaccine-induced or natural immune responses, or directly through their inclusion in a therapeutic vaccine construct.

Item Type:	Thesis (PhD)
Status:	Unpublished
Schools:	Medicine
Subjects:	Q Science > QR Microbiology > QR180 Immunology
Date of First Compliant Deposit:	30 March 2016
Last Modified:	30 Mar 2023 12:55
URI:	https://orca.cardiff.ac.uk/id/eprint/55524

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