A specialized tyrosine-based endocytosis signal in MR1 controls antigen presentation to MAIT cells-Reference-Cited by-同舟云学术

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

Published:2022-09-21 Issue:12 Volume:221 Page:
ISSN:0021-9525
Container-title:Journal of Cell Biology
language:en
Short-container-title:

Author:

Lim Hui Jing¹,Wubben Jacinta M.²,Garcia Cristian Pinero³,Cruz-Gomez Sebastian¹^ORCID,Deng Jieru¹^ORCID,Mak Jeffrey Y.W.⁴^ORCID,Hachani Abderrahman¹^ORCID,Anderson Regan J.⁵^ORCID,Painter Gavin F.⁵^ORCID,Goyette Jesse³^ORCID,Amarasinghe Shanika L.⁶⁷^ORCID,Ritchie Matthew E.⁶⁷^ORCID,Roquilly Antoine¹⁸^ORCID,Fairlie David P.⁴^ORCID,Gaus Katharina³,Rossjohn Jamie²⁹^ORCID,Villadangos Jose A.¹¹⁰^ORCID,McWilliam Hamish E.G.¹¹⁰^ORCID

Affiliation:

1. Department of Microbiology and Immunology, The University of Melbourne, The Peter Doherty Institute of Infection and Immunity, Melbourne, Victoria, Australia 1

2. Infection and Immunity Program and The Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute Monash University, Clayton, Victoria, Australia 2

3. EMBL Australia Node in Single Molecule Science, School of Medical Sciences, The University of New South Wales, Sydney, Australia 3

4. Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland, Australia 4

5. Ferrier Research Institute, Victoria University of Wellington, Wellington, New Zealand 5

6. Epigenetics and Development Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia 6

7. Department of Medical Biology, The University of Melbourne, Parkville, Victoria, Australia 7

8. Nantes Université, CHU Nantes, INSERM, Center for Research in Transplantation and Translational Immunology, UMR 1064; F-44000, Nantes, France 8

9. Institute of Infection and Immunity, Cardiff University School of Medicine, Heath Park, Cardiff, UK 9

10. Department of Biochemistry and Pharmacology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, Victoria, Australia 10

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.

Funder

National Health and Medical Research Council

Australian Research Council

ARC Centre of Excellence in Advanced Molecular Imaging

National Institutes of Health

New Zealand Ministry of Business Innovation and Employment

Horizon 2020

Publisher

Rockefeller University Press

Subject

Cell Biology

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