Selection of evolutionarily conserved mucosal-associated invariant T cells by MR1

Emmanuel Treiner; Livine Duban; Selamak Bahram; Mirjana Radosavljevic; Valerie Wanner; Florence Tilloy; Pierre Affaticati; Susan Gilfillan; Olivier Lantz

doi:10.1038/nature01433

Selection of evolutionarily conserved mucosal-associated invariant T cells by MR1

Emmanuel Treiner, Livine Duban, Selamak Bahram, Mirjana Radosavljevic, Valerie Wanner, Florence Tilloy, Pierre Affaticati, Susan Gilfillan, Olivier Lantz

Research output: Contribution to journal › Article › peer-review

884 Scopus citations

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-immunity^1,2. 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 species¹. MAIT cells are not present in germfree 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.

Original language	English
Pages (from-to)	164-169
Number of pages	6
Journal	Nature
Volume	422
Issue number	6928
DOIs	https://doi.org/10.1038/nature01433
State	Published - Mar 13 2003

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@article{08b4edb41b004c43a785b4098fbaf60a,

title = "Selection of evolutionarily conserved mucosal-associated invariant T cells by MR1",

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 species1. MAIT cells are not present in germfree 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.",

author = "Emmanuel Treiner and Livine Duban and Selamak Bahram and Mirjana Radosavljevic and Valerie Wanner and Florence Tilloy and Pierre Affaticati and Susan Gilfillan and Olivier Lantz",

note = "Funding Information: Acknowledgements We are grateful to J. Ye for providing numerous critical reagents for these studies. H. Parsons provided excellent technical assistance. Members of the de Lange laboratory are thanked for comments on this work. This work was supported by a grant from the NIH. D.L. is a recipient of an Ann Siegel Postdoctoral fellowship from the ACS. Funding Information: Acknowledgements We thank S. Laigneau, N. Froux, M. Garcia, F. Valette and I. Ciss{\'e} 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{\textquoteright}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 M{\'e}dicale, Institut National de la Sant{\'e} et de la Recherche M{\'e}dicale and Section M{\'e}dicale de l{\textquoteright}Institut Curie. S.G. thanks Hoffmann la Roche for supporting the Basel Institute for Immunology and M. Colonna for support in St Louis.",

year = "2003",

month = mar,

day = "13",

doi = "10.1038/nature01433",

language = "English",

volume = "422",

pages = "164--169",

journal = "Nature",

issn = "0028-0836",

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T1 - Selection of evolutionarily conserved mucosal-associated invariant T cells by MR1

AU - Treiner, Emmanuel

AU - Duban, Livine

AU - Bahram, Selamak

AU - Radosavljevic, Mirjana

AU - Wanner, Valerie

AU - Tilloy, Florence

AU - Affaticati, Pierre

AU - Gilfillan, Susan

AU - Lantz, Olivier

N1 - Funding Information: Acknowledgements We are grateful to J. Ye for providing numerous critical reagents for these studies. H. Parsons provided excellent technical assistance. Members of the de Lange laboratory are thanked for comments on this work. This work was supported by a grant from the NIH. D.L. is a recipient of an Ann Siegel Postdoctoral fellowship from the ACS. Funding Information: 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.

PY - 2003/3/13

Y1 - 2003/3/13

N2 - 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 species1. MAIT cells are not present in germfree 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.

AB - 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 species1. MAIT cells are not present in germfree 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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U2 - 10.1038/nature01433

DO - 10.1038/nature01433

M3 - Article

C2 - 12634786

AN - SCOPUS:0037434974

SN - 0028-0836

VL - 422

SP - 164

EP - 169

JO - Nature

JF - Nature

IS - 6928

ER -

Selection of evolutionarily conserved mucosal-associated invariant T cells by MR1

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