Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Progress
  • Published:

Co-dependents: MR1-restricted MAIT cells and their antimicrobial function

Nature Reviews Microbiology volume 11, pages 14–19 (2013)Cite this article

Subjects

Abstract

Mucosal-associated invariant T (MAIT) cells are a unique T cell subset in mammals. They are present at high frequencies at mucosal tissue sites and have an intrinsic capacity to respond to microbial infections. The semi-invariant antigen recognition receptor of MAIT cells detects the non-polymorphic antigen-presenting molecule major histocompatibility complex class I-related protein 1 (MR1), which can bind microorganism-derived riboflavin metabolites. The striking evolutionary conservation in both the MR1 molecule and the MAIT T cell receptor suggests that strong selective pressures maintain this T cell pattern recognition system which detects microbial infection.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Proposed sequence of selection, differentiation and function of MAIT cells.

Similar content being viewed by others

References

  1. Pancer, Z. & Cooper, M. D. The evolution of adaptive immunity. Annu. Rev. Immunol. 24, 497–518 (2006).

    Article  CAS  Google Scholar 

  2. Medzhitov, R. & Janeway, C. A. Jr. Decoding the patterns of self and nonself by the innate immune system. Science 296, 298–300 (2002).

    Article  CAS  Google Scholar 

  3. Kaufman, J. Evolution and immunity. Immunology 130, 459–462 (2010).

    Article  CAS  Google Scholar 

  4. Litman, G. W., Rast, J. P. & Fugmann, S. D. The origins of vertebrate adaptive immunity. Nature Rev. Immunol. 10, 543–553 (2010).

    Article  CAS  Google Scholar 

  5. Boehm, T. & Bleul, C. C. The evolutionary history of lymphoid organs. Nature Immunol. 8, 131–135 (2007).

    Article  CAS  Google Scholar 

  6. Obar, J. J. & Lefrancois, L. Memory CD8+ T cell differentiation. Ann. N. Y. Acad. Sci. 1183, 251–266 (2010).

    Article  CAS  Google Scholar 

  7. Weng, N. P., Araki, Y. & Subedi, K. The molecular basis of the memory T cell response: differential gene expression and its epigenetic regulation. Nature Rev. Immunol. 12, 306–315 (2012).

    Article  CAS  Google Scholar 

  8. Porcelli, S., Yockey, C. E., Brenner, M. B. & Balk, S. P. Analysis of T cell antigen receptor (TCR) expression by human peripheral blood CD4-8- α/β T cells demonstrates preferential use of several Vβ genes and an invariant TCR α chain. J. Exp. Med. 178, 1–16 (1993).

    Article  CAS  Google Scholar 

  9. Tilloy, F. et al. An invariant T cell receptor α chain defines a novel TAP-independent major histocompatibility complex class Ib-restricted α/β T cell subpopulation in mammals. J. Exp. Med. 189, 1907–1921 (1999).

    Article  CAS  Google Scholar 

  10. Dusseaux, M. et al. Human MAIT cells are xenobiotic-resistant, tissue-targeted, CD161hi IL-17-secreting T cells. Blood 117, 1250–1259 (2011).

    Article  CAS  Google Scholar 

  11. Gold, M. C. et al. Human mucosal associated invariant T cells detect bacterially infected cells. PLoS Biol. 8, e1000407 (2010).

    Article  Google Scholar 

  12. Benlagha, K., Kyin, T., Beavis, A., Teyton, L. & Bendelac, A. A thymic precursor to the NK T cell lineage. Science 296, 553–555 (2002).

    Article  CAS  Google Scholar 

  13. Bendelac, A., Savage, P. B. & Teyton, L. The biology of NKT cells. Annu. Rev. Immunol. 25, 297–336 (2007).

    Article  CAS  Google Scholar 

  14. Gold, M. C. et al. Human thymic MR1-restricted MAIT cells are innate pathogen-reactive effectors that adapt following thymic egress. Mucosal Immunol. 13 Jun 2012 (doi:10.1038/mi.2012.45).

    Article  Google Scholar 

  15. Martin, E. et al. Stepwise development of MAIT cells in mouse and human. PLoS Biol. 7, e54 (2009).

    Article  Google Scholar 

  16. Treiner, E. et al. Selection of evolutionarily conserved mucosal-associated invariant T cells by MR1. Nature 422, 164–169 (2003).

    Article  CAS  Google Scholar 

  17. Le Bourhis, L. et al. Antimicrobial activity of mucosal-associated invariant T cells. Nature Immunol. 11, 701–708 (2010).

    Article  CAS  Google Scholar 

  18. Kjer-Nielsen, L. et al. MR1 presents microbial vitamin B metabolites to MAIT cells. Nature 10 Oct 2012 (doi:10.1038/nature11605).

    Article  CAS  Google Scholar 

  19. Miyazaki, Y., Miyake, S., Chiba, A., Lantz, O. & Yamamura, T. Mucosal-associated invariant T cells regulate Th1 response in multiple sclerosis. Int. Immunol. 23, 529–535 (2011).

    Article  CAS  Google Scholar 

  20. Goldfinch, N. et al. Conservation of mucosal associated invariant T (MAIT) cells and the MR1 restriction element in ruminants, and abundance of MAIT cells in spleen. Vet. Res. 41, 62 (2010).

    Article  Google Scholar 

  21. Gold, M. C. et al. Human innate Mycobacterium tuberculosis-reactive αβTCR+ thymocytes. PLoS Pathog. 4, e39 (2008).

    Article  Google Scholar 

  22. Lewinsohn, D. M., Briden, A. L., Reed, S. G., Grabstein, K. H. & Alderson, M. R. Mycobacterium tuberculosis-reactive CD8+ T lymphocytes: the relative contribution of classical versus nonclassical HLA restriction. J. Immunol. 165, 925–930 (2000).

    Article  CAS  Google Scholar 

  23. Lewinsohn, D. M. et al. Characterization of human CD8+ T cells reactive with Mycobacterium tuberculosis-infected antigen-presenting cells. J. Exp. Med. 187, 1633–1640 (1998).

    Article  CAS  Google Scholar 

  24. Lewinsohn, D. M. et al. Classically restricted human CD8+ T lymphocytes derived from Mycobacterium tuberculosis-infected cells: definition of antigenic specificity. J. Immunol. 166, 439–446 (2001).

    Article  CAS  Google Scholar 

  25. Lewinsohn, D. A., Gold, M. C. & Lewinsohn, D. M. Views of immunology: effector T cells. Immunol. Rev. 240, 25–39 (2011).

    Article  CAS  Google Scholar 

  26. Georgel, P., Radosavljevic, M., Macquin, C. & Bahram, S. The non-conventional MHC class I MR1 molecule controls infection by Klebsiella pneumoniae in mice. Mol. Immunol. 48, 769–775 (2011).

    Article  CAS  Google Scholar 

  27. Chua, W. J. et al. Polyclonal MAIT cells have unique innate functions in bacterial infection. Infect. Immun. 80, 3256–3267 (2012).

    Article  CAS  Google Scholar 

  28. Smith, K., McCoy, K. D. & Macpherson, A. J. Use of axenic animals in studying the adaptation of mammals to their commensal intestinal microbiota. Semin. Immunol. 19, 59–69 (2007).

    Article  CAS  Google Scholar 

  29. Riegert, P., Wanner, V. & Bahram, S. Genomics, isoforms, expression, and phylogeny of the MHC class I-related MR1 gene. J. Immunol. 161, 4066–4077 (1998).

    CAS  PubMed  Google Scholar 

  30. Miley, M. J. et al. Biochemical features of the MHC-related protein 1 consistent with an immunological function. J. Immunol. 170, 6090–6098 (2003).

    Article  CAS  Google Scholar 

  31. Huang, S. et al. MR1 uses an endocytic pathway to activate mucosal-associated invariant T cells. J. Exp. Med. 205, 1201–1211 (2008).

    Article  CAS  Google Scholar 

  32. Yamaguchi, H., Kurosawa, Y. & Hashimoto, K. Expanded genomic organization of conserved mammalian MHC class I-related genes, human MR1 and its murine ortholog. Biochem. Biophys. Res. Commun. 250, 558–564 (1998).

    Article  CAS  Google Scholar 

  33. Huang, S. et al. MR1 antigen presentation to mucosal-associated invariant T cells was highly conserved in evolution. Proc. Natl Acad. Sci. USA 106, 8290–8295 (2009).

    Article  CAS  Google Scholar 

  34. Chua, W. J. et al. Endogenous MHC-related protein 1 is transiently expressed on the plasma membrane in a conformation that activates mucosal-associated invariant T cells. J. Immunol. 186, 4744–4750 (2011).

    Article  CAS  Google Scholar 

  35. Greenaway, H. Y. et al. NKT and MAIT invariant TCRα sequences can be produced efficiently by VJ gene recombination. Immunobiology 1 May 2012 (doi:10.1016/j.imbio.2012.04.003).

    Article  CAS  Google Scholar 

  36. Coles, M. C. & Raulet, D. H. NK1.1+ T cells in the liver arise in the thymus and are selected by interactions with class I molecules on CD4+CD8+ cells. J. Immunol. 164, 2412–2418 (2000).

    Article  CAS  Google Scholar 

  37. Reantragoon, R. et al. Structural insight into MR1-mediated recognition of the mucosal associated invariant T cell receptor. J. Exp. Med. 209, 761–774 (2012).

    Article  CAS  Google Scholar 

  38. Scott-Browne, J. P. et al. Germline-encoded recognition of diverse glycolipids by natural killer T cells. Nature Immunol. 8, 1105–1113 (2007).

    Article  CAS  Google Scholar 

  39. Borg, N. A. et al. CD1d–lipid-antigen recognition by the semi-invariant NKT T-cell receptor. Nature 448, 44–49 (2007).

    Article  CAS  Google Scholar 

  40. Mallevaey, T. et al. T cell receptor CDR2β and CDR3β loops collaborate functionally to shape the iNKT cell repertoire. Immunity 31, 60–71 (2009).

    Article  CAS  Google Scholar 

  41. Matulis, G. et al. Innate-like control of human iNKT cell autoreactivity via the hypervariable CDR3β loop. PLoS Biol. 8, e1000402 (2010).

    Article  Google Scholar 

  42. Croxford, J. L., Miyake, S., Huang, Y. Y., Shimamura, M. & Yamamura, T. Invariant Vα19i T cells regulate autoimmune inflammation. Nature Immunol. 7, 987–994 (2006).

    Article  CAS  Google Scholar 

  43. Miller, M. M. et al. Characterization of two avian MHC-like genes reveals an ancient origin of the CD1 family. Proc. Natl Acad. Sci. USA 102, 8674–8679 (2005).

    Article  CAS  Google Scholar 

  44. Salomonsen, J. et al. Two CD1 genes map to the chicken MHC, indicating that CD1 genes are ancient and likely to have been present in the primordial MHC. Proc. Natl Acad. Sci. USA 102, 8668–8673 (2005).

    Article  CAS  Google Scholar 

  45. Hee, C. S. et al. Structure of a classical MHC class I molecule that binds “non-classical” ligands. PLoS Biol. 8, e1000557 (2010).

    Article  Google Scholar 

  46. Kaech, S. M., Hemby, S., Kersh, E. & Ahmed, R. Molecular and functional profiling of memory CD8 T cell differentiation. Cell 111, 837–851 (2002).

    Article  CAS  Google Scholar 

  47. Litman, G. W. & Cooper, M. D. Why study the evolution of immunity? Nature Immunol. 8, 547–548 (2007).

    Article  CAS  Google Scholar 

  48. Marrack, P., Scott-Browne, J. P., Dai, S., Gapin, L. & Kappler, J. W. Evolutionarily conserved amino acids that control TCR-MHC interaction. Annu. Rev. Immunol. 26, 171–203 (2008).

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Marielle C. Gold and David M. Lewinsohn are at the Division of Pulmonary & Critical Care Medicine, Oregon Health & Science University, Portland VA Medical Center, 3710 SW US Veterans Hospital Road, Portland, Oregon 97239, USA.,

    Marielle C. Gold & David M. Lewinsohn

Authors
  1. Marielle C. Gold
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. David M. Lewinsohn
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Marielle C. Gold or David M. Lewinsohn.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Related links

Related links

FURTHER INFORMATION

Marielle C. Gold's homepage

David M. Lewinsohn's homepage

Rights and permissions

Reprints and permissions

About this article

Cite this article

Gold, M., Lewinsohn, D. Co-dependents: MR1-restricted MAIT cells and their antimicrobial function. Nat Rev Microbiol 11, 14–19 (2013). https://doi.org/10.1038/nrmicro2918

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrmicro2918

This article is cited by

Search

Advanced search

Quick links

Nature Briefing Microbiology

Sign up for the Nature Briefing: Microbiology newsletter — what matters in microbiology research, free to your inbox weekly.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing: Microbiology