Biology subjects

Tiffeau-Mayer, A.

Publications and source records attributed to Tiffeau-Mayer, A..

3 recordsLinked to original sources

bioRxiv2025

Evolution of T cell responses in the tuberculin skin test reveals generalisable Mtb-reactive T cell metaclones.

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.

immunology↗

bioRxiv2024

Tissue determinants of the human T cell receptor repertoire.

98% of T cells reside in tissues, yet nearly all human T cell analyses are performed from peripheral blood. We single-cell sequenced 5.7 million T cells from ten donors autologous blood and tonsils and sought to answer key questions about T cell receptor biology previously unanswerable by smaller-scale experiments. We identified distinct clonal expansions and distributions in blood compared to tonsils, with surprisingly low (1-7%) clonal sharing. These few shared clones exhibited divergent phenotypes across bodily sites. Analysis of antigen-specific CD8 T cells revealed location as a main determinant of frequency, phenotype, and immunodominance. Finally, diversity estimates from the tissue recalibrates current repertoire diversity estimates, and we provide a refined estimate of whole-body repertoire. Given the tissue-restricted nature of T cell phenotypes, functions, differentiation, and clonality revealed by this dataset, we conclude that tissue analyses are crucial for accurate repertoire analysis and monitoring changes after perturbing therapies.

immunology↗

bioRxiv2024

Intra- and inter-chain contacts determine TCR specificity: applying protein co-evolution methods to TCRαβ pairing

The six complementarity determining regions (CDRs) of the T cell receptor (TCR) form multiple contacts with cognate peptide and major histocompatibility complex, thus determining antigen specificity. However, the contacts between the CDRs themselves are less understood. We perform a systematic study of all available TCR structures, and identify consistent patterns of intra- and inter-chain CDR contacts. We further show that the sequences of paired TCR and TCR{beta} are not independent within sets of antigen-specific TCRs, for most epitopes. We quantify this sequence restriction using a mutual information framework. Co-evolution models can achieve some de novo prediction of TCR/TCR{beta} pairing, without using a training set of known pairs. The conserved pattern of CDR amino acid contacts, and the mutual sequence constraints between antigen-specific sets of T cell receptor and {beta} chains could play an important role in shaping the antigen-specific T cell repertoire.

immunology↗