A specialized tyrosine-based endocytosis signal in MR1 controls antigen presentation to MAIT cells

Hui Jing Lim; Jacinta M. Wubben; Cristian Pinero Garcia; Sebastian Cruz-Gomez; Jieru Deng; Jeffrey Y.W. Mak; Abderrahman Hachani; Regan J. Anderson; Gavin F. Painter; Jesse Goyette; Shanika L. Amarasinghe; Matthew E. Ritchie; Antoine Roquilly; David P. Fairlie; Katharina Gaus; Jamie Rossjohn; Jose A. Villadangos; Hamish E.G. McWilliam

doi:10.1083/jcb.202110125

A specialized tyrosine-based endocytosis signal in MR1 controls antigen presentation to MAIT cells

Hui Jing Lim, Jacinta M. Wubben, Cristian Pinero Garcia, Sebastian Cruz-Gomez, Jieru Deng, Jeffrey Y.W. Mak, Abderrahman Hachani, Regan J. Anderson, Gavin F. Painter, Jesse Goyette, Shanika L. Amarasinghe, Matthew E. Ritchie, Antoine Roquilly, David P. Fairlie, Katharina Gaus, Jamie Rossjohn, Jose A. Villadangos, Hamish E.G. McWilliam

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Abstract

MR1 is a highly conserved microbial immune-detection system in mammals. It captures vitamin B-related metabolite antigens from diverse microbes and presents them at the cell surface to stimulate MR1-restricted lymphocytes including mucosal-associated invariant T (MAIT) cells. MR1 presentation and MAIT cell recognition mediate homeostasis through host defense and tissue repair. The cellular mechanisms regulating MR1 cell surface expression are critical to its function and MAIT cell recognition, yet they are poorly defined. Here, we report that human MR1 is equipped with a tyrosine-based motif in its cytoplasmic domain that mediates low affinity binding with the endocytic adaptor protein 2 (AP2) complex. This interaction controls the kinetics of MR1 internalization from the cell surface and minimizes recycling. We propose MR1 uses AP2 endocytosis to define the duration of antigen presentation to MAIT cells and the detection of a microbial metabolic signature by the immune system.

Original language	English
Article number	e202110125
Number of pages	24
Journal	Journal of Cell Biology
Volume	221
Issue number	12
DOIs	https://doi.org/10.1083/jcb.202110125
Publication status	Published - 5 Dec 2022

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Lim, H. J., Wubben, J. M., Garcia, C. P., Cruz-Gomez, S., Deng, J., Mak, J. Y. W., Hachani, A., Anderson, R. J., Painter, G. F., Goyette, J., Amarasinghe, S. L., Ritchie, M. E., Roquilly, A., Fairlie, D. P., Gaus, K., Rossjohn, J., Villadangos, J. A., & McWilliam, H. E. G. (2022). A specialized tyrosine-based endocytosis signal in MR1 controls antigen presentation to MAIT cells. Journal of Cell Biology, 221(12), Article e202110125. https://doi.org/10.1083/jcb.202110125

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title = "A specialized tyrosine-based endocytosis signal in MR1 controls antigen presentation to MAIT cells",

abstract = "MR1 is a highly conserved microbial immune-detection system in mammals. It captures vitamin B-related metabolite antigens from diverse microbes and presents them at the cell surface to stimulate MR1-restricted lymphocytes including mucosal-associated invariant T (MAIT) cells. MR1 presentation and MAIT cell recognition mediate homeostasis through host defense and tissue repair. The cellular mechanisms regulating MR1 cell surface expression are critical to its function and MAIT cell recognition, yet they are poorly defined. Here, we report that human MR1 is equipped with a tyrosine-based motif in its cytoplasmic domain that mediates low affinity binding with the endocytic adaptor protein 2 (AP2) complex. This interaction controls the kinetics of MR1 internalization from the cell surface and minimizes recycling. We propose MR1 uses AP2 endocytosis to define the duration of antigen presentation to MAIT cells and the detection of a microbial metabolic signature by the immune system.",

author = "Lim, {Hui Jing} and Wubben, {Jacinta M.} and Garcia, {Cristian Pinero} and Sebastian Cruz-Gomez and Jieru Deng and Mak, {Jeffrey Y.W.} and Abderrahman Hachani and Anderson, {Regan J.} and Painter, {Gavin F.} and Jesse Goyette and Amarasinghe, {Shanika L.} and Ritchie, {Matthew E.} and Antoine Roquilly and Fairlie, {David P.} and Katharina Gaus and Jamie Rossjohn and Villadangos, {Jose A.} and McWilliam, {Hamish E.G.}",

note = "Publisher Copyright: {\textcopyright} 2022 Lim et al.",

year = "2022",

month = dec,

day = "5",

doi = "10.1083/jcb.202110125",

language = "English",

volume = "221",

journal = "Journal of Cell Biology",

issn = "0021-9525",

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Lim, HJ, Wubben, JM, Garcia, CP, Cruz-Gomez, S, Deng, J, Mak, JYW, Hachani, A, Anderson, RJ, Painter, GF, Goyette, J, Amarasinghe, SL, Ritchie, ME, Roquilly, A, Fairlie, DP, Gaus, K, Rossjohn, J, Villadangos, JA & McWilliam, HEG 2022, 'A specialized tyrosine-based endocytosis signal in MR1 controls antigen presentation to MAIT cells', Journal of Cell Biology, vol. 221, no. 12, e202110125. https://doi.org/10.1083/jcb.202110125

TY - JOUR

T1 - A specialized tyrosine-based endocytosis signal in MR1 controls antigen presentation to MAIT cells

AU - Lim, Hui Jing

AU - Wubben, Jacinta M.

AU - Garcia, Cristian Pinero

AU - Cruz-Gomez, Sebastian

AU - Deng, Jieru

AU - Mak, Jeffrey Y.W.

AU - Hachani, Abderrahman

AU - Anderson, Regan J.

AU - Painter, Gavin F.

AU - Goyette, Jesse

AU - Amarasinghe, Shanika L.

AU - Ritchie, Matthew E.

AU - Roquilly, Antoine

AU - Fairlie, David P.

AU - Gaus, Katharina

AU - Rossjohn, Jamie

AU - Villadangos, Jose A.

AU - McWilliam, Hamish E.G.

PY - 2022/12/5

Y1 - 2022/12/5

N2 - MR1 is a highly conserved microbial immune-detection system in mammals. It captures vitamin B-related metabolite antigens from diverse microbes and presents them at the cell surface to stimulate MR1-restricted lymphocytes including mucosal-associated invariant T (MAIT) cells. MR1 presentation and MAIT cell recognition mediate homeostasis through host defense and tissue repair. The cellular mechanisms regulating MR1 cell surface expression are critical to its function and MAIT cell recognition, yet they are poorly defined. Here, we report that human MR1 is equipped with a tyrosine-based motif in its cytoplasmic domain that mediates low affinity binding with the endocytic adaptor protein 2 (AP2) complex. This interaction controls the kinetics of MR1 internalization from the cell surface and minimizes recycling. We propose MR1 uses AP2 endocytosis to define the duration of antigen presentation to MAIT cells and the detection of a microbial metabolic signature by the immune system.

AB - MR1 is a highly conserved microbial immune-detection system in mammals. It captures vitamin B-related metabolite antigens from diverse microbes and presents them at the cell surface to stimulate MR1-restricted lymphocytes including mucosal-associated invariant T (MAIT) cells. MR1 presentation and MAIT cell recognition mediate homeostasis through host defense and tissue repair. The cellular mechanisms regulating MR1 cell surface expression are critical to its function and MAIT cell recognition, yet they are poorly defined. Here, we report that human MR1 is equipped with a tyrosine-based motif in its cytoplasmic domain that mediates low affinity binding with the endocytic adaptor protein 2 (AP2) complex. This interaction controls the kinetics of MR1 internalization from the cell surface and minimizes recycling. We propose MR1 uses AP2 endocytosis to define the duration of antigen presentation to MAIT cells and the detection of a microbial metabolic signature by the immune system.

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JO - Journal of Cell Biology

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M1 - e202110125

ER -

A specialized tyrosine-based endocytosis signal in MR1 controls antigen presentation to MAIT cells

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ARC Centre of Excellence in Advanced Molecular Imaging

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A specialized tyrosine-based endocytosis signal in MR1 controls antigen presentation to MAIT cells

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ARC Centre of Excellence in Advanced Molecular Imaging

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