Turner, Carolin T;
Tiffeau-Mayer, Andreas;
Rosenheim, Joshua;
Chandran, Aneesh;
Saxena, Rishika;
Zhang, Ping;
Jiang, Jana;
... Noursadeghi, Mahdad; + view all
(2026)
Evolution of the tuberculin skin test reveals generalisable Mtb-reactive T cell metaclones.
Nature Communications
10.1038/s41467-026-68678-9.
(In press).
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Abstract
T cells contribute to immune protection and pathogenesis in tuberculosis, but measurements of polyclonal responses have failed to resolve correlates of outcome. We report the temporal evaluation of the human in vivo clonal repertoire of Mycobacterium tuberculosis (Mtb)-reactive T cell responses, by T cell receptor (TCR) sequencing at the site of the tuberculin skin test, as a model for a standardised antigenic challenge. Initial non-selective recruitment of T cells is followed by enrichment of Mtb-reactive clones arising from oligoclonal T cell proliferation. We introduce a modular computational pipeline, Metaclonotypist, to sensitively cluster distinct TCRs with shared epitope specificity, which we apply here to establish a catalogue of public Mtb-reactive HLA-restricted T cell metaclones. Although most in vivo Mtb-reactive T cells are private, 10 metaclones were sufficient to identify Mtb-T cell reactivity across our study population (N≥128), indicating striking population level immunodominance of specific TCR-peptide interactions that may inform patient stratification and vaccine development.
| Type: | Article |
|---|---|
| Title: | Evolution of the tuberculin skin test reveals generalisable Mtb-reactive T cell metaclones |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1038/s41467-026-68678-9 |
| Publisher version: | https://doi.org/10.1038/s41467-026-68678-9 |
| Language: | English |
| Additional information: | © The Author(s) 2026. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. |
| Keywords: | Clonal selection, Gene regulation in immune cells, T-cell receptor, Tuberculosis |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10220625 |
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