Imperial College London
Alternate

Emeritus ProfessorMurraySelkirk

Faculty of Natural Sciences, Department of Life Sciences

Emeritus Professor in Molecular Parasitology
 
 
 
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Contact

 

+44 (0)20 7594 5214m.selkirk Website

 
 
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Location

 

204Sir Ernst Chain BuildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Almeida-Santos:2022:10.1101/2022.07.21.500987,
author = {Almeida-Santos, J and Berkachy, R and Tye, CA and Hassan, J and Kalfaoglu, B and Selkirk, ME and Ono, M},
doi = {10.1101/2022.07.21.500987},
title = {Temporal profiling of CD4 T-cell activation and differentiation upon SARS-CoV-2 spike protein immunisation},
url = {http://dx.doi.org/10.1101/2022.07.21.500987},
year = {2022}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - <jats:title>ABSTRACT</jats:title><jats:p>CD4 T-cells require T-cell receptor (TCR) signalling for their activation and differentiation. Foxp3+ regulatory T-cells (Treg) are dependent on TCR signals for their differentiation and suppressive function. However, it is not fully known how TCR signalling controls the differentiation of polyclonal CD4 T-cells upon antigen recognition at the single-cell level in vivo. In this study, using Nr4a3-Tocky (<jats:underline>T</jats:underline>imer-<jats:underline>o</jats:underline>f-<jats:underline>c</jats:underline>ell-<jats:underline>k</jats:underline>inetics-and-activit<jats:underline>y</jats:underline>), which analyses temporal changes of antigen-reactive T-cells following TCR signalling, we investigated T-cell response to Spike protein fragments (S1a, S1b, S2a, and S2b) upon immunisation. We show that S1a and S2a induced the differentiation of PD1<jats:sup>hi</jats:sup>CXCR5<jats:sup>+</jats:sup> T follicular helper (Tfh) cells, which is related to CD4 T-cell immunogenicity. In contrast, S1b induced CD25<jats:sup>hi</jats:sup>GITR<jats:sup>hi</jats:sup>PD-1<jats:sup>int</jats:sup> Treg, which intermittently received TCR signalling. Using Foxp3-Tocky, which analyses <jats:italic>Foxp3</jats:italic> transcriptional dynamics, the S1b-reactive Treg sustained <jats:italic>Foxp3</jats:italic> transcription over time, which is a hallmark of activated Treg. Foxp3 fate-mapping showed that the S1b-reactive Treg were derived not from pre-existing thymic Treg, suggesting Foxp3 induction in non-Treg cells. Thus, the current study reveals temporally dynamic differentiation of CD4 T-cells and Treg upon immunisation in the polyclonal TCR repertoire.</jats:p>
AU  - Almeida-Santos,J
AU  - Berkachy,R
AU  - Tye,CA
AU  - Hassan,J
AU  - Kalfaoglu,B
AU  - Selkirk,ME
AU  - Ono,M
DO  - 10.1101/2022.07.21.500987
PY  - 2022///
TI  - Temporal profiling of CD4 T-cell activation and differentiation upon SARS-CoV-2 spike protein immunisation
UR  - http://dx.doi.org/10.1101/2022.07.21.500987
ER  -
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