Evolution of T cell responses in the tuberculin skin test reveals generalisable Mtb-reactive T cell metaclones DOI Creative Commons
Carolin T. Turner, Andreas Mayer, Joshua Rosenheim

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: April 18, 2025

Abstract T cells contribute to immune protection and pathogenesis in tuberculosis, but measurements of polyclonal responses have failed resolve correlates outcome. We report the first temporal evaluation human vivo clonal repertoire Mtb-reactive cell responses, by receptor (TCR) sequencing at site a standardised antigenic challenge. Initial recruitment non-Mtb reactive is followed enrichment clones arising from oligoclonal proliferation. introduce modular computational pipeline, Metaclonotypist, sensitively cluster distinct TCRs with shared epitope specificity, which we apply here establish catalogue public HLA-restricted metaclones. Although most are private, 10 metaclones were sufficient identify Mtb-T reactivity across our study population (N≥128), indicating striking level immunodominance specific TCR-peptide interactions that may offer novel approaches patient stratification vaccine development.

Language: Английский

Evolution of T cell responses in the tuberculin skin test reveals generalisable Mtb-reactive T cell metaclones DOI Creative Commons
Carolin T. Turner, Andreas Mayer, Joshua Rosenheim

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: April 18, 2025

Abstract T cells contribute to immune protection and pathogenesis in tuberculosis, but measurements of polyclonal responses have failed resolve correlates outcome. We report the first temporal evaluation human vivo clonal repertoire Mtb-reactive cell responses, by receptor (TCR) sequencing at site a standardised antigenic challenge. Initial recruitment non-Mtb reactive is followed enrichment clones arising from oligoclonal proliferation. introduce modular computational pipeline, Metaclonotypist, sensitively cluster distinct TCRs with shared epitope specificity, which we apply here establish catalogue public HLA-restricted metaclones. Although most are private, 10 metaclones were sufficient identify Mtb-T reactivity across our study population (N≥128), indicating striking level immunodominance specific TCR-peptide interactions that may offer novel approaches patient stratification vaccine development.

Language: Английский

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