A Tail of MR1 Internalization — ASN Events
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  3. A Tail of MR1 Internalization

A Tail of MR1 Internalization (#111)

Jacinta M Wubben 1 2 3 , Hamish EG McWilliam 4 , Jerome Le Nours 1 2 3 , James McCluskey 4 , Jose A Villadangos 4 5 , Jamie Rossjohn 1 2 3 6
  1. Infection and Immunity Program, Biomedicine Discovery Institute, Monash University, Clayton, VIC, Australia
  2. Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC, Australia
  3. Australian Research Council (ARC) Centre of Excellence in Advanced Molecular Imaging, Monash University, Clayton, VIC, Australia
  4. Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Parkville, VIC, Australia
  5. Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, VIC, Australia
  6. Institute of Infection and Immunity, Cardiff University School of Medicine, Cardiff, United Kingdom

MR1 is a MHC-I like molecule that is ubiquitously expressed in a number of cell types and presents exogenous vitamin B metabolites to MAIT cells. Recently, it has been determined that MR1 resides in the endoplasmic reticulum until it binds its antigen, then is trafficked through the Golgi to be presented at the cell surface. After cell surface presentation, approximately 65% of MR1 is internalized within 4 hours and is degraded via endocytosis. Nonetheless, a small percentage (~5%) is recycled from the endosome to the cell surface, which provides an opportunity for ligand exchange to occur. 

While the cellular pathway of internalization and recycling of MR1 is now known, the molecular mechanism of internalization is still unclear. Consequently, the aim of this study was to identify the sequence motifs within the cytoplasmic tail of MR1 that is required for internalization. To investigate this, a series of stable C1R cell lines overexpressing mutants of the cytoplasmic tail of MR1 were created via retroviral transduction and characterized for the ability of these forms to traffic to and from the cell surface. No significant difference was observed in the ability of the mutant MR1 molecules to traffic to the cell surface compared to the wild-type MR1. However, different mutants of the cytoplasmic tail resulted in variations in the rate of internalization of MR1. These findings suggest that there are multiple mechanisms contributing to the internalization of MR1 from the cell surface, which will need to be further investigated.