Innate-like T cell subset commitment in the murine thymus is independent of TCR characteristics and occurs during proliferation - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Proceedings of the National Academy of Sciences of the United States of America Année : 2024

Innate-like T cell subset commitment in the murine thymus is independent of TCR characteristics and occurs during proliferation

Résumé

How T-cell receptor (TCR) characteristics determine subset commitment during T-cell development is still unclear. Here, we addressed this question for innate-like T cells, mucosal-associated invariant T (MAIT) cells, and invariant natural killer T (iNKT) cells. MAIT and iNKT cells have similar developmental paths, leading in mice to two effector subsets, cytotoxic (MAIT1/iNKT1) and IL17-secreting (MAIT17/iNKT17). For iNKT1 vs iNKT17 fate choice, an instructive role for TCR affinity was proposed but recent data argue against this model. Herein, we examined TCR role in MAIT and iNKT subset commitment through scRNAseq and TCR repertoire analysis. In our dataset of thymic MAIT cells, we found pairs of T-cell clones with identical amino acid TCR sequences originating from distinct precursors, one of which committed to MAIT1 and the other to MAIT17 fates. Quantitative in silico simulations indicated that the number of such cases is best explained by lineage choice being independent of TCR characteristics. Comparison of TCR features of MAIT1 and MAIT17 clonotypes demonstrated that the subsets cannot be distinguished based on TCR sequence. To pinpoint the developmental stage associated with MAIT sublineage choice, we demonstrated that proliferation takes place both before and after MAIT fate commitment. Altogether, we propose a model of MAIT cell development in which noncommitted, intermediate-stage MAIT cells undergo a first round of proliferation, followed by TCR characteristics-independent commitment to MAIT1 or MAIT17 lineage, followed by an additional round of proliferation. Reanalyzing a published iNKT TCR dataset, we showed that this model is also relevant for iNKT cell development.

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Dates et versions

hal-04532544 , version 1 (04-04-2024)

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Vadim K. Karnaukhov, Anne‐laure Le Gac, Linda Bilonda Mutala, Aurelie Darbois, Laetitia Perrin, et al.. Innate-like T cell subset commitment in the murine thymus is independent of TCR characteristics and occurs during proliferation. Proceedings of the National Academy of Sciences of the United States of America, 2024, 121 (14), ⟨10.1073/pnas.2311348121⟩. ⟨hal-04532544⟩
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