Human MAIT-cell responses to Escherichia coli: activation, cytokine production, proliferation, and cytotoxicity

J Leukoc Biol. 2016 Jul;100(1):233-40. doi: 10.1189/jlb.4TA0815-391RR. Epub 2016 Mar 31.

Abstract

Mucosa-associated invariant T cells are a large and relatively recently described innate-like antimicrobial T-cell subset in humans. These cells recognize riboflavin metabolites from a range of microbes presented by evolutionarily conserved major histocompatibility complex, class I-related molecules. Given the innate-like characteristics of mucosa-associated invariant T cells and the novel type of antigens they recognize, new methodology must be developed and existing methods refined to allow comprehensive studies of their role in human immune defense against microbial infection. In this study, we established protocols to examine a range of mucosa-associated invariant T-cell functions as they respond to antigen produced by Escherichia coli These improved and dose- and time-optimized experimental protocols allow detailed studies of MR1-dependent mucosa-associated invariant T-cell responses to Escherichia coli pulsed antigen-presenting cells, as assessed by expression of activation markers and cytokines, by proliferation, and by induction of apoptosis and death in major histocompatibility complex, class I-related-expressing target cells. The novel and optimized protocols establish a framework of methods and open new possibilities to study mucosa-associated invariant T-cell immunobiology, using Escherichia coli as a model antigen. Furthermore, we propose that these robust experimental systems can also be adapted to study mucosa-associated invariant T-cell responses to other microbes and types of antigen-presenting cells.

Keywords: MR1; antimicrobial activity; functional evaluation; innate-like T cells.

MeSH terms

  • Antigen-Presenting Cells / immunology*
  • Antigen-Presenting Cells / metabolism
  • Antigens, Bacterial / immunology*
  • Antigens, Bacterial / metabolism
  • Cells, Cultured
  • Cytokines / metabolism
  • Escherichia coli / immunology*
  • Escherichia coli / metabolism
  • Escherichia coli Infections / immunology*
  • Escherichia coli Infections / metabolism
  • Escherichia coli Infections / microbiology
  • Histocompatibility Antigens Class I / metabolism
  • Humans
  • Lymphocyte Activation
  • Minor Histocompatibility Antigens / immunology*
  • Minor Histocompatibility Antigens / metabolism
  • Mucosal-Associated Invariant T Cells / immunology*
  • Mucosal-Associated Invariant T Cells / metabolism
  • Receptors, Antigen, T-Cell / metabolism
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / metabolism

Substances

  • Antigens, Bacterial
  • Cytokines
  • Histocompatibility Antigens Class I
  • MR1 protein, human
  • Minor Histocompatibility Antigens
  • Receptors, Antigen, T-Cell