Type I interferons are important co-stimulatory signals during T cell receptor mediated human MAIT cell activation

Eur J Immunol. 2020 Feb;50(2):178-191. doi: 10.1002/eji.201948279. Epub 2019 Nov 14.


Mucosal associated invariant T (MAIT) cells are abundant unconventional T cells that can be stimulated either via their TCR or by innate cytokines. The MAIT cell TCR recognises a pyrimidine ligand, derived from riboflavin synthesising bacteria, bound to MR1. In infection, bacteria not only provide the pyrimidine ligand but also co-stimulatory signals, such as TLR agonists, that can modulate TCR-mediated activation. Recently, type I interferons (T1-IFNs) have been identified as contributing to cytokine-mediated MAIT cell activation. However, it is unknown whether T1-IFNs also have a role during TCR-mediated MAIT cell activation. In this study, we investigated the co-stimulatory role of T1-IFNs during TCR-mediated activation of MAIT cells by the MR1 ligand 5-amino-6-d-ribitylaminouracil/methylglyoxal. We found that T1-IFNs were able to boost interferon-γ and granzyme B production in 5-amino-6-d-ribitylaminouracil/methylglyoxal-stimulated MAIT cells. Similarly, influenza virus-induced T1-IFNs enhanced TCR-mediated MAIT cell activation. An essential role of T1-IFNs in regulating MAIT cell activation by riboflavin synthesising bacteria was also demonstrated. The co-stimulatory role of T1-IFNs was also evident in liver-derived MAIT cells. T1-IFNs acted directly on MAIT cells to enhance their response to TCR stimulation. Overall, our findings establish an important immunomodulatory role of T1-IFNs during TCR-mediated MAIT cell activation.

Keywords: TCR activation; co-stimulation; influenza virus; mucosal associated invariant T cells; type I interferons.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cells, Cultured
  • Cytokines / immunology
  • Humans
  • Immunity, Innate / immunology
  • Interferon Type I / immunology*
  • Interferon-gamma / immunology
  • Ligands
  • Lymphocyte Activation / immunology
  • Mucosal-Associated Invariant T Cells / immunology*
  • Receptors, Antigen, T-Cell / immunology*


  • Cytokines
  • Interferon Type I
  • Ligands
  • Receptors, Antigen, T-Cell
  • Interferon-gamma