Identification of phenotypically and functionally heterogeneous mouse mucosal-associated invariant T cells using MR1 tetramers

J Exp Med. 2015 Jun 29;212(7):1095-108. doi: 10.1084/jem.20142110. Epub 2015 Jun 22.


Studies on the biology of mucosal-associated invariant T cells (MAIT cells) in mice have been hampered by a lack of specific reagents. Using MR1-antigen (Ag) tetramers that specifically bind to the MR1-restricted MAIT T cell receptors (TCRs), we demonstrate that MAIT cells are detectable in a broad range of tissues in C57BL/6 and BALB/c mice. These cells include CD4(-)CD8(-), CD4(-)CD8(+), and CD4(+)CD8(-) subsets, and their frequency varies in a tissue- and strain-specific manner. Mouse MAIT cells have a CD44(hi)CD62L(lo) memory phenotype and produce high levels of IL-17A, whereas other cytokines, including IFN-γ, IL-4, IL-10, IL-13, and GM-CSF, are produced at low to moderate levels. Consistent with high IL-17A production, most MAIT cells express high levels of retinoic acid-related orphan receptor γt (RORγt), whereas RORγt(lo) MAIT cells predominantly express T-bet and produce IFN-γ. Most MAIT cells express the promyelocytic leukemia zinc finger (PLZF) transcription factor, and their development is largely PLZF dependent. These observations contrast with previous reports that MAIT cells from Vα19 TCR transgenic mice are PLZF(-) and express a naive CD44(lo) phenotype. Accordingly, MAIT cells from normal mice more closely resemble human MAIT cells than previously appreciated, and this provides the foundation for further investigations of these cells in health and disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Proliferation
  • Cytokines / metabolism
  • Histocompatibility Antigens Class I / metabolism*
  • Histological Techniques
  • Kruppel-Like Transcription Factors / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Minor Histocompatibility Antigens
  • Mucous Membrane / cytology
  • Mucous Membrane / immunology*
  • Natural Killer T-Cells / cytology
  • Natural Killer T-Cells / metabolism*
  • Promyelocytic Leukemia Zinc Finger Protein
  • Receptors, Antigen, T-Cell / metabolism*
  • Species Specificity


  • Cytokines
  • Histocompatibility Antigens Class I
  • Kruppel-Like Transcription Factors
  • Minor Histocompatibility Antigens
  • Mr1 protein, mouse
  • Promyelocytic Leukemia Zinc Finger Protein
  • Receptors, Antigen, T-Cell
  • Zbtb16 protein, mouse