The αβTCR repertoire at scale in the immgenT dataset

Abstract

The immense T cell receptor (TCR) repertoire is shaped by VDJ combinatorial diversity, imprecise rearrangements, and clonal selection. The immgenT Project generated scRNA and TCRseq to map paired {beta}TCR repertoires across 734 mouse samples from diverse tissues and challenge conditions. Compositional analysis uncovered some extreme junctional architectures. Beyond probabilistic V and J pairing, over-represented joins suggested non-randomness in fine joining, broadening the precedent of quasi-invariant iNKT and MAIT TCRs. We charted public clonotypes linked to self or environmental antigens in the main lineages. Tissue analyses revealed compartmentalized tissue-specific expansions. Unproductive and productive rearrangements of a V gene appeared to interfere specifically with each other, at chromatin or RNA levels. Unexpectedly, allelic exclusion at TCR{beta} proved less stringent than thought, and we identified rearrangements of TCR in immature pre-T stages. This organism-wide look into the TCR repertoire offers novel insights on the evolutionary and immunological pressures on TCR repertoire selection.