Evolution of T cell responses in the tuberculin skin test reveals generalisable Mtb-reactive T cell metaclones.
Turner, C. T.; Tiffeau-Mayer, A.; Rosenheim, J.; Chandran, A.; Saxena, R.; Zhang, P.; Jiang, J.; Berkeley, M.; Pang, F.; Uddin, I.; Nageswaran, G.; Byrne, S.; Karthikeyan, A.; Smidt, W.; Ogongo, P.; Byng-Maddick, R.; Capocci, S.; Lipman, M.; Kunst, H.; Lozewicz, S.; Rasmussen, V.; Pollara, G.; Knight, J. C.; Leslie, A.; Chain, B. M.; Noursadeghi, M.
Show 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 first temporal evaluation of the human in vivo clonal repertoire of Mtb-reactive T cell responses, by T cell receptor (TCR) sequencing at the site of a standardised antigenic challenge. Initial recruitment of non-Mtb reactive 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 offer novel approaches to patient stratification and vaccine development.
Matching journals
The top 5 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- APMAT analysis reveals the association between CD8 T cell receptors, cognate antigen, and T cell phenotype and persistence 97%
- Deep learning predictions of TCR-epitope interactions reveal epitope-specific chains in dual alpha T cells 97%
- Multiomic single-cell sequencing defines tissue-specific responses in Stevens-Johnson Syndrome and Toxic epidermal necrolysis. 96%
Similar papers in this journal
Similar papers in this journal
- Human thymopoiesis produces polyspecific CD8+ alfa/beta T cells responding to multiple viral antigens 97%
- Patient-derived xenografts and single-cell sequencing identifies three subtypes of tumor-reactive lymphocytes in uveal melanoma metastases 96%
- Chromatin conformation dynamics during CD4+ T cell activation implicates autoimmune disease-associated genes and regulatory elements 96%
Similar papers in this journal
- Quality of vaccination-induced T cell responses is conveyed by polyclonality and high, but not maximum, antigen receptor avidity 97%
- Single-cell immune profiling reveals novel thymus-seeding populations, T cell commitment, and multi-lineage development in the human thymus 96%
- Redefining CD4 T cell residency: Helper T cells orchestrate protective humoral immunity in the lung 96%
Similar papers in this journal
- The pseudokinase Trib1 regulates the transition of exhausted T cells to a KLR+ CD8+ effector state and its deletion improves checkpoint blockade 95%
- Distinct mutational processes shape selection of MHC class I and class II mutations across primary and metastatic tumors 95%
- The Observed T cell receptor Space database enables paired-chain repertoire mining, coherence analysis and language modelling 95%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.