UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

Variation in T cell Immunity in Health

Shaw, Emily; (2022) Variation in T cell Immunity in Health. Doctoral thesis (Ph.D), UCL (University College London). Green open access

[thumbnail of SHAW_10160872_thesis_combined.pdf]
Preview
Text
SHAW_10160872_thesis_combined.pdf

Download (17MB) | Preview

Abstract

Introduction Bacillus Calmette–Guérin (BCG)-vaccination affords variable protection against tuberculosis (TB), which is unexplained. The project hypothesises that there is inter-individual variation in both the naïve T cell (NTC) response to a standard stimulation and in the ‘trained’ immune response of BCG-vaccine-primed T cells on secondary exposure to antigen and that relationships exist between the two. The aim of the study is to identify factors by which T cell vaccine design may be improved. Methods Blood was collected from 107 adults immediately prior to BCG-vaccination. NTCs were enriched from pre-BCG frozen/thawed peripheral blood mononuclear cells (PBMC), subjected to anti-CD3/CD28 stimulation and then characterised by fluorescence-activated cell-sorting (FACS) on markers of activation, differentiation and proliferation. Participants were then re-bled eight weeks later and their frozen/thawed PBMC incubated with purified protein derivative (PPD) in three separate assays before FACS to measure activation induced markers, Th1 cytokines and proliferation. A DNA sequencing pipeline and computational analysis were employed to examine 67 participants’ peripheral blood TCR repertoires in response to BCG. Results There was inter-individual variation amongst all pre-vaccination NTC stimulation assay parameters, some of which were strongly positively correlated. In the post-BCG-vaccination assays, all parameters were significantly upregulated in response to incubation with PPD and demonstrated wide ranges of inter-individual variation. In both sets of assays, results were found to be reproducible and inter-individual variation surpassed technical noise. Post-BCG expanded TCRs generated clusters of homologous sequences, were shared between multiple participants and shared homology with annotated TB-specific TCRs. Discussion There is inter-individual variation in multiple parameters to standard NTC stimulation, possibly reflecting intrinsic variance in the T cell intracellular signalling capacity. BCG has variable T cell immunogenicity, which may bear relation to pre-vaccination parameters. BCG-vaccination induces a polyclonal population of T cells with the ability to recognise mycobacterial antigens. Improved understanding of the T cell component to variable BCG vaccine efficacy may aid next generation TB vaccine development.

Type: Thesis (Doctoral)
Qualification: Ph.D
Title: Variation in T cell Immunity in Health
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Copyright © The Author 2022. Original content in this thesis is licensed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) Licence (https://creativecommons.org/licenses/by-nc/4.0/). Any third-party copyright material present remains the property of its respective owner(s) and is licensed under its existing terms. Access may initially be restricted at the author’s request.
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity
URI: https://discovery.ucl.ac.uk/id/eprint/10160872
Downloads since deposit
Loading...
57Downloads
Download activity - last month
Loading...
Download activity - last 12 months
Loading...
Downloads by country - last 12 months
1.United States
6
2.United Kingdom
5
3.India
2
4.Argentina
1
5.Russian Federation
1
6.China
1
7.Taiwan
1
8.Germany
1

Archive Staff Only

View Item View Item