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The αβTCR repertoire at scale in the immgenT dataset

Croze, M.; Yang, L.; Candeias, S.; Magill, I.; Casey, O.; Piekarsa, V.; Vijaykumar, B.; Giudicelli, V.; Kossida, S.; Zemmour, D.; Benoist, C.; Project, i.

2026-02-02 immunology
10.64898/2026.01.30.702900 bioRxiv
Show abstract

The immensity of the T cell receptor (TCR) repertoire, shaped by combinatorial diversity, imprecise rearrangements, and clonal selection, makes it difficult to comprehend. The immgenT Project generated single-cell RNA and TCRseq to map paired {beta}TCR repertoires across 734 mouse T cell samples from diverse tissues, lineages and challenge conditions. Compositional analysis uncovered some extreme junctional architectures. Previously unreported recurrent recombinations suggested non-randomness in VDJ joining, broadening the precedent of quasi-invariant iNKT and MAIT TCRs. These, with public clonotypes linked to self or environmental factors, contribute to a highly skewed distribution of clonotype frequencies. Tissue analyses reveal compartmentalized and tissue-specific clonal expansions. Unproductive rearrangements of one V gene appeared to suppress the rearrangements of the same V gene on the second chromosome, suggesting that unproductive TCR transcripts may act as regulatory lncRNAs. This organism-wide look into the TCR repertoire offers novel insights on the evolutionary and immunological pressures on repertoire selection.

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