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

Neller, Michelle A., Ladell, Kristin, McLaren, James E., Matthews, Katherine K., Gostick, Emma, Pentier, Johanne M., Dolton, Garry, Schauenburg, Andrea J.A., Koning, Dan, Fontaine Costa, Ana Isabel C.A., Watkins, Thomas S., Venturi, Vanessa, Smith, Corey, Khanna, Rajiv, Miners, Kelly, Clement, Mathew, Wooldridge, Linda, Cole, David K., van Baarle, Debbie, Sewell, Andrew K., Burrows, Scott R., Price, David A., and Miles, John J. (2015) Naive CD8⁺ T-cell precursors display structured TCR repertoires and composite antigen-driven selection dynamics. Immunology and Cell Biology, 93 (7). pp. 625-633.

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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 ID: 44967
Item Type: Article (Research - C1)
ISSN: 1440-1711
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This work is licensed under a Creative Commons Attribution 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/4.0/

Funders: Wellcome Trust (WT), National Health and Medical Research Council (NHMRC), Biotechnology and Biological Sciences Research Council (BBSRC)
Projects and Grants: NHMRC Grant APP613664, BBSRC Grant BB/H001085/1
Date Deposited: 03 Aug 2016 22:59
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1107 Immunology > 110702 Applied Immunology (incl Antibody Engineering, Xenotransplantation and T-cell Therapies) @ 100%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920108 Immune System and Allergy @ 100%
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