A three-stage intrathymic development pathway for the mucosal-associated invariant T cell lineage

Hui Fern Koay; Nicholas A. Gherardin; Anselm Enders; Liyen Loh; Laura K. Mackay; Catarina F. Almeida; Brendan E. Russ; Claudia A. Nold-Petry; Marcel F. Nold; Sammy Bedoui; Zhenjun Chen; Alexandra J. Corbett; Sidonia B.G. Eckle; Bronwyn Meehan; Yves D'Udekem; Igor E. Konstantinov; Martha Lappas; Ligong Liu; Chris C. Goodnow; David P. Fairlie; Jamie Rossjohn; Mark M. Chong; Katherine Kedzierska; Stuart P. Berzins; Gabrielle T. Belz; James McCluskey; Adam P. Uldrich; Dale I. Godfrey; Daniel G. Pellicci

doi:10.1038/ni.3565

A three-stage intrathymic development pathway for the mucosal-associated invariant T cell lineage

Hui Fern Koay, Nicholas A. Gherardin, Anselm Enders, Liyen Loh, Laura K. Mackay, Catarina F. Almeida, Brendan E. Russ, Claudia A. Nold-Petry, Marcel F. Nold, Sammy Bedoui, Zhenjun Chen, Alexandra J. Corbett, Sidonia B.G. Eckle, Bronwyn Meehan, Yves D'Udekem, Igor E. Konstantinov, Martha Lappas, Ligong Liu, Chris C. Goodnow, David P. FairlieJamie Rossjohn, Mark M. Chong, Katherine Kedzierska, Stuart P. Berzins, Gabrielle T. Belz, James McCluskey, Adam P. Uldrich, Dale I. Godfrey, Daniel G. Pellicci^*

^*Corresponding author for this work

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

274 Citations (Scopus)

Abstract

Mucosal-associated invariant T cells (MAIT cells) detect microbial vitamin B2 derivatives presented by the antigen-presenting molecule MR1. Here we defined three developmental stages and checkpoints for the MAIT cell lineage in humans and mice. Stage 1 and stage 2 MAIT cells predominated in thymus, while stage 3 cells progressively increased in abundance extrathymically. Transition through each checkpoint was regulated by MR1, whereas the final checkpoint that generated mature functional MAIT cells was controlled by multiple factors, including the transcription factor PLZF and microbial colonization. Furthermore, stage 3 MAIT cell populations were expanded in mice deficient in the antigen-presenting molecule CD1d, suggestive of a niche shared by MAIT cells and natural killer T cells (NKT cells). Accordingly, this study maps the developmental pathway and checkpoints that control the generation of functional MAIT cells.

Original language	English
Pages (from-to)	1300-1311
Number of pages	12
Journal	Nature Immunology
Volume	17
Issue number	11
DOIs	https://doi.org/10.1038/ni.3565
Publication status	Published - 19 Oct 2016

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Koay, H. F., Gherardin, N. A., Enders, A., Loh, L., Mackay, L. K., Almeida, C. F., Russ, B. E., Nold-Petry, C. A., Nold, M. F., Bedoui, S., Chen, Z., Corbett, A. J., Eckle, S. B. G., Meehan, B., D'Udekem, Y., Konstantinov, I. E., Lappas, M., Liu, L., Goodnow, C. C., ... Pellicci, D. G. (2016). A three-stage intrathymic development pathway for the mucosal-associated invariant T cell lineage. Nature Immunology, 17(11), 1300-1311. https://doi.org/10.1038/ni.3565

@article{dd28d8609b3e41bf9d0ab23d6f3d4dc7,

title = "A three-stage intrathymic development pathway for the mucosal-associated invariant T cell lineage",

abstract = "Mucosal-associated invariant T cells (MAIT cells) detect microbial vitamin B2 derivatives presented by the antigen-presenting molecule MR1. Here we defined three developmental stages and checkpoints for the MAIT cell lineage in humans and mice. Stage 1 and stage 2 MAIT cells predominated in thymus, while stage 3 cells progressively increased in abundance extrathymically. Transition through each checkpoint was regulated by MR1, whereas the final checkpoint that generated mature functional MAIT cells was controlled by multiple factors, including the transcription factor PLZF and microbial colonization. Furthermore, stage 3 MAIT cell populations were expanded in mice deficient in the antigen-presenting molecule CD1d, suggestive of a niche shared by MAIT cells and natural killer T cells (NKT cells). Accordingly, this study maps the developmental pathway and checkpoints that control the generation of functional MAIT cells.",

author = "Koay, {Hui Fern} and Gherardin, {Nicholas A.} and Anselm Enders and Liyen Loh and Mackay, {Laura K.} and Almeida, {Catarina F.} and Russ, {Brendan E.} and Nold-Petry, {Claudia A.} and Nold, {Marcel F.} and Sammy Bedoui and Zhenjun Chen and Corbett, {Alexandra J.} and Eckle, {Sidonia B.G.} and Bronwyn Meehan and Yves D'Udekem and Konstantinov, {Igor E.} and Martha Lappas and Ligong Liu and Goodnow, {Chris C.} and Fairlie, {David P.} and Jamie Rossjohn and Chong, {Mark M.} and Katherine Kedzierska and Berzins, {Stuart P.} and Belz, {Gabrielle T.} and James McCluskey and Uldrich, {Adam P.} and Godfrey, {Dale I.} and Pellicci, {Daniel G.}",

year = "2016",

month = oct,

day = "19",

doi = "10.1038/ni.3565",

language = "English",

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journal = "Nature Immunology",

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Koay, HF, Gherardin, NA, Enders, A, Loh, L, Mackay, LK, Almeida, CF, Russ, BE, Nold-Petry, CA, Nold, MF, Bedoui, S, Chen, Z, Corbett, AJ, Eckle, SBG, Meehan, B, D'Udekem, Y, Konstantinov, IE, Lappas, M, Liu, L, Goodnow, CC, Fairlie, DP, Rossjohn, J, Chong, MM, Kedzierska, K, Berzins, SP, Belz, GT, McCluskey, J, Uldrich, AP, Godfrey, DI & Pellicci, DG 2016, 'A three-stage intrathymic development pathway for the mucosal-associated invariant T cell lineage', Nature Immunology, vol. 17, no. 11, pp. 1300-1311. https://doi.org/10.1038/ni.3565

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T1 - A three-stage intrathymic development pathway for the mucosal-associated invariant T cell lineage

AU - Koay, Hui Fern

AU - Gherardin, Nicholas A.

AU - Enders, Anselm

AU - Loh, Liyen

AU - Mackay, Laura K.

AU - Almeida, Catarina F.

AU - Russ, Brendan E.

AU - Nold-Petry, Claudia A.

AU - Nold, Marcel F.

AU - Bedoui, Sammy

AU - Chen, Zhenjun

AU - Corbett, Alexandra J.

AU - Eckle, Sidonia B.G.

AU - Meehan, Bronwyn

AU - D'Udekem, Yves

AU - Konstantinov, Igor E.

AU - Lappas, Martha

AU - Liu, Ligong

AU - Goodnow, Chris C.

AU - Fairlie, David P.

AU - Rossjohn, Jamie

AU - Chong, Mark M.

AU - Kedzierska, Katherine

AU - Berzins, Stuart P.

AU - Belz, Gabrielle T.

AU - McCluskey, James

AU - Uldrich, Adam P.

AU - Godfrey, Dale I.

AU - Pellicci, Daniel G.

PY - 2016/10/19

Y1 - 2016/10/19

N2 - Mucosal-associated invariant T cells (MAIT cells) detect microbial vitamin B2 derivatives presented by the antigen-presenting molecule MR1. Here we defined three developmental stages and checkpoints for the MAIT cell lineage in humans and mice. Stage 1 and stage 2 MAIT cells predominated in thymus, while stage 3 cells progressively increased in abundance extrathymically. Transition through each checkpoint was regulated by MR1, whereas the final checkpoint that generated mature functional MAIT cells was controlled by multiple factors, including the transcription factor PLZF and microbial colonization. Furthermore, stage 3 MAIT cell populations were expanded in mice deficient in the antigen-presenting molecule CD1d, suggestive of a niche shared by MAIT cells and natural killer T cells (NKT cells). Accordingly, this study maps the developmental pathway and checkpoints that control the generation of functional MAIT cells.

AB - Mucosal-associated invariant T cells (MAIT cells) detect microbial vitamin B2 derivatives presented by the antigen-presenting molecule MR1. Here we defined three developmental stages and checkpoints for the MAIT cell lineage in humans and mice. Stage 1 and stage 2 MAIT cells predominated in thymus, while stage 3 cells progressively increased in abundance extrathymically. Transition through each checkpoint was regulated by MR1, whereas the final checkpoint that generated mature functional MAIT cells was controlled by multiple factors, including the transcription factor PLZF and microbial colonization. Furthermore, stage 3 MAIT cell populations were expanded in mice deficient in the antigen-presenting molecule CD1d, suggestive of a niche shared by MAIT cells and natural killer T cells (NKT cells). Accordingly, this study maps the developmental pathway and checkpoints that control the generation of functional MAIT cells.

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U2 - 10.1038/ni.3565

DO - 10.1038/ni.3565

M3 - Article

SN - 1529-2908

VL - 17

SP - 1300

EP - 1311

JO - Nature Immunology

JF - Nature Immunology

IS - 11

ER -

A three-stage intrathymic development pathway for the mucosal-associated invariant T cell lineage

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