A specialized tyrosine-based endocytosis signal in MR1 controls antigen presentation to MAIT cells
Hui Jing Lim
(1)
,
Jacinta Wubben
(2)
,
Cristian Pinero Garcia
(3)
,
Sebastian Cruz-Gomez
(1)
,
Jieru Deng
(1)
,
Jeffrey Y.W. Mak
(4)
,
Abderrahman Hachani
(1)
,
Regan Anderson
(5)
,
Gavin Painter
(5)
,
Jesse Goyette
(3)
,
Shanika Amarasinghe
(6, 1)
,
Matthew Ritchie
(6, 1)
,
Antoine Roquilly
(7, 8, 1)
,
David Fairlie
(4)
,
Katharina Gaus
(3)
,
Jamie Rossjohn
(2, 9)
,
Jose Villadangos
(1)
,
Hamish E.G. Mcwilliam
(1)
1
University of Melbourne
2 Monash University [Clayton]
3 UNSW - University of New South Wales [Sydney]
4 UQ [All campuses : Brisbane, Dutton Park Gatton, Herston, St Lucia and other locations] - The University of Queensland
5 Victoria University of Wellington
6 WEHI - The Walter and Eliza Hall Institute of Medical Research
7 CHU Nantes - Centre Hospitalier Universitaire de Nantes
8 U1064 Inserm - CR2TI - Team 6 : Impact of acute inflammation on host pathogen interactions and lung homeostasis
9 Cardiff University
2 Monash University [Clayton]
3 UNSW - University of New South Wales [Sydney]
4 UQ [All campuses : Brisbane, Dutton Park Gatton, Herston, St Lucia and other locations] - The University of Queensland
5 Victoria University of Wellington
6 WEHI - The Walter and Eliza Hall Institute of Medical Research
7 CHU Nantes - Centre Hospitalier Universitaire de Nantes
8 U1064 Inserm - CR2TI - Team 6 : Impact of acute inflammation on host pathogen interactions and lung homeostasis
9 Cardiff University
Sebastian Cruz-Gomez
- Fonction : Auteur
- PersonId : 1197279
- ORCID : 0000-0001-8853-2295
Jeffrey Y.W. Mak
- Fonction : Auteur
- PersonId : 1197281
- ORCID : 0000-0002-8011-4539
Abderrahman Hachani
- Fonction : Auteur
- PersonId : 1197282
- ORCID : 0000-0001-8032-2154
Regan Anderson
- Fonction : Auteur
- PersonId : 1197283
- ORCID : 0000-0003-3467-9202
Gavin Painter
- Fonction : Auteur
- PersonId : 1197284
- ORCID : 0000-0002-1310-7769
Jesse Goyette
- Fonction : Auteur
- PersonId : 1197285
- ORCID : 0000-0002-1008-1890
Shanika Amarasinghe
- Fonction : Auteur
- PersonId : 1197286
- ORCID : 0000-0002-2229-8106
Matthew Ritchie
- Fonction : Auteur
- PersonId : 1197287
- ORCID : 0000-0002-7383-0609
Antoine Roquilly
- Fonction : Auteur
- PersonId : 767046
- ORCID : 0000-0002-1029-6242
- IdRef : 14637939X
David Fairlie
- Fonction : Auteur
- PersonId : 821743
- ORCID : 0000-0002-7856-8566
Jamie Rossjohn
- Fonction : Auteur
- PersonId : 778059
- ORCID : 0000-0002-2020-7522
Jose Villadangos
- Fonction : Auteur
- PersonId : 1197288
- ORCID : 0000-0001-6771-8891
Hamish E.G. Mcwilliam
- Fonction : Auteur
- PersonId : 1197289
- ORCID : 0000-0003-3479-3419
Résumé
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.