DOI: 10.5522/04/28049606
title: Evolution of the tuberculin skin test reveals generalisable Mtb-reactive T cell metaclones

description: This dataset collection contains all de novo T cell receptor sequence (TCR) data, in processed format, used for analysis in our TST TCR manuscript (https://doi.org/10.1038/s41467-026-68678-9). A metadata file (<code>metadata.csv</code>) is included that provides annotations for each filename of individual samples. The data were generated with two different methods, and comprise several data subsets:<b>Dataset 1:</b> Bulk TCR sequencing data generated with the UCL Chain lab protocol. The raw data files for these samples will be available at the NCBI Sequence Read Archive, accession number PRJNA1208718, upon peer-reviewed publication of the manuscript. The processed data files, available here, were generated using Decombinator v4 (https://github.com/innate2adaptive/Decombinator).Alpha and beta chain sequences from whole blood of n=20 adults with latent tuberculosis (TB) infectionAlpha and beta chain sequences from skin punch biopsies taken 2-3 days after tuberculin skin test (TST) injection in n=17 adults with latent TB infectionAlpha and beta chain sequences from skin punch biopsies taken 7 days after TST injection in n=165 adults with latent TB infectionAlpha and beta chain sequences from cultured PBMC of n=12 adults with latent TB infection, stimulated for 6 days with one of 10 µg/mL purified protein derivative of Mtb, 100 µg/mL tetanus toxoid, or control buffer, yielding between 1-5 replicates per participant per stimulus.Individual sample data files are provided in <code>.tsv.gz</code> format. In addition, for convenience, combined data files of full or down-sampled single-chain repertoires are provided, which allow full reproducibility of the analyses presented in the manuscript, using analysis code on https://github.com/carolinturner/tst_tcr. Full repertoires = <code>combined_alpha.csv.gz</code> and <code>combined_beta.csv.gz</code>; Repertoires down-sampled to 16,000 TCRs each = <code>combined_subsampled_alpha.csv.gz</code> and <code>combined_subsampled_beta.csv.gz</code>; Repertoires down-sampled to between 5,000 and 10,000 TCRs for metaclone discovery = <code>combined_subsampled_5000_10000_beta.csv.gz</code>.<b>Dataset 2:</b> Bulk TCR sequencing data generated with Adaptive Biotechnologies' ImmunoSEQ assay. The raw data files for these samples are not made available by the third party provider. The processed data files, available here, were downloaded from the ImmunoSEQ website.Beta chain sequences from lung tissue resections of n=13 adults with TB disease. Up to 3 samples per patient, scored for disease severity by physician.Beta chain sequences from control lung tissue resections of n=3 adults with lung cancer without TB disease. Up to 2 samples per patient, including tumour and healthy margin samples.Beta chain sequences from blood of n=11 adults with TB disease and n=3 adults with lung cancer without TB disease. Up to 2 replicate samples per patient.Beta chain sequences from CD4 T cells, flow-sorted from lung or blood of n=5 adults with TB disease, and additionally separated by expression of tissue residency marker CD69.Individual sample files are provided in <code>.tsv</code> format. For convenience, a combined data file is provided for beta chain repertoires (<code>ImmunoSeq_combined_beta.csv.gz</code>).<br>