Naive CD8+ T-cell precursors display structured TCR repertoires and composite antigen-driven selection dynamics

Neller, Michelle A., Ladell, Kristin Ingrid ORCID: https://orcid.org/0000-0002-9856-2938, McLaren, James Edward ORCID: https://orcid.org/0000-0002-7021-5934, Matthews, Katherine K., Gostick, Emma, Pentier, Johanne, Dolton, Garry Michael, Schauenburg, Andrea J. A., Koning, Dan, Fontaine Costa, Ana Isabel C. A., Watkins, Thomas S., Venturi, Vanessa, Smith, Corey, Khanna, Rajiv, Miners, Kelly Louise, Clement, Mathew ORCID: https://orcid.org/0000-0002-9280-5281, Wooldridge, Linda, Cole, David ORCID: https://orcid.org/0000-0003-0028-9396, van Baarle, Debbie, Sewell, Andrew K. ORCID: https://orcid.org/0000-0003-3194-3135, Burrows, Scott R., Price, David ORCID: https://orcid.org/0000-0001-9416-2737 and Miles, John James 2015. Naive CD8+ T-cell precursors display structured TCR repertoires and composite antigen-driven selection dynamics. Immunology and Cell Biology 93 , pp. 625-633. 10.1038/icb.2015.17

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Abstract

Basic parameters of the naive antigen (Ag)-specific T-cell repertoire in humans remain poorly defined. Systematic characterization of this ‘ground state’ immunity in comparison with memory will allow a better understanding of clonal selection during immune challenge. Here, we used high-definition cell isolation from umbilical cord blood samples to establish the baseline frequency, phenotype and T-cell antigen receptor (TCR) repertoire of CD8+ T-cell precursor populations specific for a range of viral and self-derived Ags. Across the board, these precursor populations were phenotypically naive and occurred with hierarchical frequencies clustered by Ag specificity. The corresponding patterns of TCR architecture were highly ordered and displayed partial overlap with adult memory, indicating biased structuring of the T-cell repertoire during Ag-driven selection. Collectively, these results provide new insights into the complex nature and dynamics of the naive T-cell compartment.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Biosciences Medicine Systems Immunity Research Institute (SIURI)
Additional Information:	This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.
Publisher:	Nature Publishing Group
ISSN:	0818-9641
Funders:	BBSRC
Date of First Compliant Deposit:	30 March 2016
Date of Acceptance:	22 January 2015
Last Modified:	15 May 2024 01:17
URI:	https://orca.cardiff.ac.uk/id/eprint/74261

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