Abstract
The evolutionary conservation of T lymphocyte subsets bearing T-cell receptors (TCRs) using invariant α-chains is indicative of unique functions. CD1d-restricted natural killer T (NK-T) cells that express an invariant Vα14 TCRα chain have been implicated in microbial and tumour responses, as well as in auto-immunity1,2. Here we show that T cells that express the canonical hVα7.2-Jα33 or mVα19-Jα33 TCR rearrangement3 are preferentially located in the gut lamina propria of humans and mice, respectively, and are therefore genuine mucosal-associated invariant T (MAIT) cells. Selection and/or expansion of this population requires B lymphocytes, as MAIT cells are absent in B-cell-deficient patients and mice. In addition, we show that MAIT cells are selected and/or restricted by MR1, a monomorphic major histocompatibility complex class I-related molecule that is markedly conserved in diverse mammalian species4. MAIT cells are not present in germ-free mice, indicating that commensal flora is required for their expansion in the gut lamina propria. This indicates that MAIT cells are probably involved in the host response at the site of pathogen entry, and may regulate intestinal B-cell activity.
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Acknowledgements
We thank S. Laigneau, N. Froux, M. Garcia, F. Valette and I. Cissé for managing the mouse colonies in Paris, E. Wagner and colleagues for animal care at the Basel Institute for Immunology, C. DeSouza for help in the membrane biotinylation, Z. Maciorowski for cell sorting, and S. Kuschert and A. Dierich for blastocyst injection. We thank F. Ledeist for patient blood samples, N. Brousse and F. Geissman for human biopsies, P. A. Cazenave's group for xid and JH knockout mice, and K. Rajewsky for the Cre transgenic mice. We thank M. Bonneville, S. Amigorena, C. Thery, P. Benaroch, M. Colonna, D. Freemont and T. Hansen for discussions and for reviewing the manuscript. This work was supported by grants from the Association de la Recherche Contre la Cancer, Fondation pour la Recherche Médicale, Institut National de la Santé et de la Recherche Médicale and Section Médicale de l'Institut Curie. S.G. thanks Hoffmann la Roche for supporting the Basel Institute for Immunology and M. Colonna for support in St Louis.Authors' contributions S. Gilfillan and O. Lantz share senior authorship.
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41586_2003_BFnature01433_MOESM5_ESM.jpg
Supplementary Figure S5: Phenotype of T and B cells from the spleen, LPL, PP and peritenoal cavity of MR1-/- mouse (JPG 122 kb)
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Treiner, E., Duban, L., Bahram, S. et al. Selection of evolutionarily conserved mucosal-associated invariant T cells by MR1. Nature 422, 164–169 (2003). https://doi.org/10.1038/nature01433
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DOI: https://doi.org/10.1038/nature01433
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