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A Single Cell Approach to TCR Signal Strength


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Abstract

Cytotoxic T lymphocytes (CTLs) play a key role in the cell-mediated immune response against virally-infected and tumourigenic cells, killing their targets through the release of cytolytic granules. T cell receptor (TCR) recognition of foreign peptides presented by Class I MHC molecules stimulates naïve CD8+ T cell differentiation to effector cells and triggers the cytolytic activity of effector CTLs. Signal transduction downstream of the TCR is a highly diverse and coordinated network of post-translational protein modifications that ultimately drive transcriptional, translational, metabolic and cytoskeletal changes in the cell. How cytotoxic T cells coordinate their molecular machinery in response to strong versus weak stimuli remains unclear. Utilising single-cell methods including mass cytometry and single-cell RNA-sequencing, this study demonstrates how naïve and restimulated cytotoxic T cells coordinate their responses against peptides of differing stimulation strengths.

Description

Date

2024-01-01

Advisors

Griffiths, Gillian

Keywords

CTL, Cytof, Cytotoxic T cells, mass cytometry, signal strength, signalling, single cell, TCR

Qualification

Doctor of Philosophy (PhD)

Awarding Institution

University of Cambridge
Sponsorship
Wellcome Trust (204017/Z/16/Z)
Isaac Newton Trust (14.38(c))
Addenbrooke's Charitable Trust (ACT) (Minute 23/17 A (ii))