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Review
. 2018 Dec:84:58-64.
doi: 10.1016/j.semcdb.2017.11.028.

MR1-dependent antigen presentation

Elham Karamooz  1 , Melanie J Harriff  2 , David M Lewinsohn  3
Affiliations
Review

MR1-dependent antigen presentation

Elham Karamooz et al. Semin Cell Dev Biol. 2018 Dec.

Abstract

MR1 is a non-classical class I molecule that is highly conserved among mammals. Though discovered in 1995, only recently have MR1 ligands and antigens for MR1-restricted T cells been described. Unlike the traditional class I molecules HLA-A, -B, and -C, little MR1 is on the cell surface. Rather, MR1 resides in discrete intracellular vesicles and the endoplasmic reticulum, and can present non-peptidic small molecules such as those found in the riboflavin biosynthesis pathway. Since mammals do not synthesize riboflavin, MR1 can serve as a sensor of the microbial metabolome and could be key to the early detection of intracellular infection. This review will summarize the current understanding of MR1-dependent antigen presentation.

Keywords: Antigen presentation; MR1; Mucosal associated invariant T cells.

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Figures

Fig. 1.
Fig. 1.
Model of MR1 trafficking. A) MR1 is synthesized in the endoplasmic reticulum and passes through the Golgi where it either (1) goes directly to the plasma membrane or (2) remains in an intracellular vesicle. Whether an endogenous ligand facilitates MR1 egress from the ER is not known. MR1 at the plasma membrane may recycle back into the cytoplasm via recycling endsomes. MR1 vesicles may then be loaded with antigens from Mtb and then translocate to the plasma membrane. It is also possible that some MR1 ligands from Mtb are transported to the ER (3) via an unknown mechanism and are then loaded onto MR1. Syntaxin 18 is a vesicular trafficking protein involved in ER to Golgi transport. VAMP4 and Rab6 are vesicular trafficking proteins involved in endosome to trans-Golgi trafficking. Knockdown of all three of these vesicular trafficking proteins resulted in a decrease in MR1-dependent antigen presentation in the setting of Mtb infection. B) exogenous ligands traverse the cell membrane and are loaded onto MR1 in the endoplasmic reticulum. These ligands may be endocytosed or interact with specific transporters that shuttle them to MR1. After loading, MR1 passes from an Endo-H sensitive state to a post-Golgi, Endo-H resistant state, on its way to the plasma membrane. Syntaxin 18 knockdown affects 6-FP mediated translocation of MR1 to the cell surface.
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References

    1. Hashimoto K, Hirai M, Kurosawa Y, A gene outside the human MHC related to classical HLA class I genes, Science 269 (5224) (1995) 693–695. - PubMed
    1. Parra-Cuadrado JF, Navarro P, Mirones I, Setién F, Oteo M, Martínez-Naves E, A study on the polymorphism of human MHC class I-related MR1 gene and identification of an MR1-like pseudogene, Tissue Antigens. 56 (2) (2000. August) 170–172. - PubMed
    1. Tsukamoto K, Deakin JE, Graves JA, Hashimoto K, Exceptionally high conservation of the MHC class I-related gene, MR1, among mammals, Immunogenetics 65 (2) (2013. February) 115–124. - PubMed
    1. Riegert P, Wanner V, Bahram S, Genomics, isoforms, expression, and phylogeny of the MHC class I-related MR1 gene, J. Immunol. 161 (8) (1998. October 15) 4066–4077. - PubMed
    1. Walter L, Günther E, Isolation and molecular characterization of the rat MR1 homologue, a non-MHC-linked class I-related gene, Immunogenetics 47 (6) (1998. May) 477–482. - PubMed

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