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MR1 antigen presentation to MAIT cells and other MR1-restricted T cells

Nature Reviews Immunology volume 24, pages 178–192 (2024)Cite this article

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Abstract

MHC antigen presentation plays a fundamental role in adaptive and semi-invariant T cell immunity. Distinct MHC molecules bind antigens that differ in chemical structure, origin and location and present them to specialized T cells. MHC class I-related protein 1 (MR1) presents a range of small molecule antigens to MR1-restricted T (MR1T) lymphocytes. The best studied MR1 ligands are derived from microbial metabolism and are recognized by a major class of MR1T cells known as mucosal-associated invariant T (MAIT) cells. Here, we describe the MR1 antigen presentation pathway: the known types of antigens presented by MR1, the location where MR1–antigen complexes form, the route followed by the complexes to the cell surface, the mechanisms involved in termination of MR1 antigen presentation and the accessory cellular proteins that comprise the MR1 antigen presentation machinery. The current road map of the MR1 antigen presentation pathway reveals potential strategies for therapeutic manipulation of MR1T cell function and provides a foundation for further studies that will lead to a deeper understanding of MR1-mediated immunity.

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Fig. 1: Proposed immune outcomes for MR1 presentation of metabolite antigens in vivo.
Fig. 2: Major classes of ligands presented by MR1.
Fig. 3: The MR1 trafficking pathway and associated cellular machinery.
Fig. 4: An intracellular pool of ligand-receptive MR1 molecules enables a strong antigen presentation signal.

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Acknowledgements

H.E.G.M. discloses support for the research of this work from the National Health and Medical Research Council of Australia (NHMRC) (2003192). J.A.V. discloses support for the research of this work from the Australian Research Council (ARC) (DP170102471), the NHMRC (1113293 and 1058193) and the National Institute of Allergy and Infectious Diseases of the National Institutes of Health (NIH) (R01AI148407).

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

    Hamish E. G. McWilliam & Jose A. Villadangos

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

    Hamish E. G. McWilliam & Jose A. Villadangos

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McWilliam, H.E.G., Villadangos, J.A. MR1 antigen presentation to MAIT cells and other MR1-restricted T cells. Nat Rev Immunol 24, 178–192 (2024). https://doi.org/10.1038/s41577-023-00934-1

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