Cardiff University | Prifysgol Caerdydd ORCA
Online Research @ Cardiff 
WelshClear Cookie - decide language by browser settings

Novel unconventional T-cells in response to bacteria and cancer

Crowther, Michael 2018. Novel unconventional T-cells in response to bacteria and cancer. PhD Thesis, Cardiff University.
Item availability restricted.

[img] PDF
Restricted to Repository staff only until 4 February 2022 due to copyright restrictions.

Download (12MB)
[img] PDF - Supplemental Material
Restricted to Repository staff only

Download (227kB)

Abstract

Conventional T-cells respond to peptide antigens presented by person-specific Human Leukocyte Antigens (HLAs) and therefore therapies that harness such cells may only be applicable to a minority of individuals. Unconventional T-cells could bypass this limitation to provide an opportunity for population-wide disease treatments. Exploitation of such T-cells first requires a detailed study of the unconventional T-cells involved in the immune response. I therefore sought to characterise novel invariant T-cells generated in response to varied disease agents. Results – An optimised protocol for procurement of disease-relevant unconventional T-cells was established and used to generate T-cell lines and clones of interest. T-cell receptor (TCR) sequencing of unconventional T-cell populations revealed a predominance of mucosal-associated invariant cells and Vγ9Vδ2 T-cells. Enrichments for other shared TCR clonotypes included TRAV21 and TRAV13-1 genes, which have some evidence of an invariant nature. I identified an interesting T-cell clone that was capable of recognising a broad range of target cells through a novel mechanism. The ligand recognised by these T-cells was identified using a whole genome CRISPR approach. Further studies confirmed the nature of the ligand and that recognition was dependent on a new subtype of TCR that was present in all donors tested. Conclusions - The field of unconventional T-cells is rapidly expanding, with novel invariant T-cells proving to be a much greater part of the T-cell repertoire than previously estimated. New and undiscovered invariant T-cell subsets are likely to provide exciting novel immunotherapies and bypass the limitation of HLA-restriction that is associated with conventional T-cell recognition of peptide-major histocompatibility complex ligands.

Item Type: Thesis (PhD)
Date Type: Submission
Status: Unpublished
Schools: Medicine
Funders: Health and Care Research Wales
Last Modified: 04 Feb 2019 14:44
URI: http://orca-mwe.cf.ac.uk/id/eprint/119167

Actions (repository staff only)

Edit Item Edit Item

Downloads

Downloads per month over past year

View more statistics