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

HJ Lim; JM Wubben; CP Garcia; S Cruz-Gomez; J Deng; JYW Mak; A Hachani; RJ Anderson; GF Painter; J Goyette; SL Amarasinghe; ME Ritchie; A Roquilly; DP Fairlie; K Gaus; J Rossjohn; JA Villadangos; HEG McWilliam

Journal article

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

HJ Lim, JM Wubben, CP Garcia, S Cruz-Gomez, J Deng, JYW Mak, A Hachani, RJ Anderson, GF Painter, J Goyette, SL Amarasinghe, ME Ritchie, A Roquilly, DP Fairlie, K Gaus, J Rossjohn, JA Villadangos, HEG McWilliam

Journal of Cell Biology | ROCKEFELLER UNIV PRESS | Published : 2022

DOI: 10.1083/jcb.202110125

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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 (AP..

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University of Melbourne Researchers

Jieru Deng Author

Abdou Hachani Author

Matthew Ritchie Author

Antoine Roquilly Author

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Grants

Awarded by National Institutes of Health

Funding Acknowledgements

E.G. McWilliam is supported by a National Health and Medical Research Council (NHMRC) Ideas Grant (2003192), and J.A. Villadangos is supported by research grants from the Australian Research Council (ARC; DP170102471), NHMRC (1113293), and an NHMRC Senior Research Fellowship (1058193). D.P. Fairlie is an NHMRC Senior Principal Research Fellow (1117017). A. Hachani acknowledges support from a Horizon 2020_MSCA Global Fellowship grant (657766). D.P. Fairlie and J. Rossjohn acknowledge support from the ARC Centre of Excellence in Advanced Molecular Imaging (CE140100011). J.A. Villadangos, J. Rossjohn, and D.P. Fairlie are supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health (R01AI148407). J. Rossjohn is supported by an ARC Australian Laureate Fellowship, and G.F. Painter is supported by the New Zealand Ministry of Business Innovation and Employment (RTVU 1603).