title: Human MAIT-cell responses to Escherichia coli: activation, cytokine production, proliferation, and cytotoxicity.
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.
authors.affiliation: Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
authors.forename: Joana
authors.initials: J
authors.lastname: Dias
authors.affiliation: Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
authors.forename: Michał J
authors.initials: MJ
authors.lastname: Sobkowiak
authors.affiliation: Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
authors.forename: Johan K
authors.initials: JK
authors.lastname: Sandberg
authors.affiliation: Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden edwin.leeansyah@ki.se.
authors.forename: Edwin
authors.initials: E
authors.lastname: Leeansyah
mesh_terms: D000938:Antigen-Presenting Cells / Q000276:immunology* / Q000378:metabolism; D000942:Antigens, Bacterial / Q000276:immunology* / Q000378:metabolism; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D004926:Escherichia coli / Q000276:immunology* / Q000378:metabolism; D004927:Escherichia coli Infections / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D006801:Humans; D008213:Lymphocyte Activation; D015778:Minor Histocompatibility Antigens / Q000276:immunology* / Q000378:metabolism; D000072336:Mucosal-Associated Invariant T Cells / Q000276:immunology* / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism
chemical_list: D000942:Antigens, Bacterial; D016207:Cytokines; D015395:Histocompatibility Antigens Class I; C094840:MR1 protein, human; D015778:Minor Histocompatibility Antigens; D011948:Receptors, Antigen, T-Cell
keywords: MR1; antimicrobial activity; functional evaluation; innate-like T cells