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

Michelle A Neller, Kristin Ladell, James E McLaren, Katherine K Matthews, Emma Gostick, Joanne M Pentier, Garry Dolton, Andrea JA Schauenburg, Dan Koning, Ana Costa, Thomas Watkins, Vanessa Venturi, Corey Smith, Rajiv Khanna, Kelly Miners, Matthew Clement, Linda Wooldridge, David K Cole, Debbie van Baarle, Andrew K SewellScott R Burrows, David A Price, John J Miles

Research output: Contribution to journalArticle (Academic Journal)peer-review

29 Citations (Scopus)
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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.
Original languageEnglish
Pages (from-to)625-633
Number of pages9
JournalImmunology and Cell Biology
Volume93
Issue number7
Early online date24 Mar 2015
DOIs
Publication statusPublished - Aug 2015

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