Tuning of human MAIT cell activation by commensal bacteria species and MR1-dependent T-cell presentation.

Authors

Cihan Tastan
Ece Karhan, The Jackson LaboratoryFollow
Wei Zhou, The Jackson LaboratoryFollow
Elizabeth Fleming, The Jackson LaboratoryFollow
Anita Y Voigt, The Jackson LaboratoryFollow
Xudong Yao
Lei Wang
Meghan Horne
Lindsey Placek, The Jackson LaboratoryFollow
Lina Kozhaya, The Jackson LaboratoryFollow
Julia Oh, The Jackson LaboratoryFollow
Derya Unutmaz, The Jackson LaboratoryFollow

Document Type

Article

Publication Date

11-1-2018

Keywords

JGM

JAX Location

Reprint Collection

JAX Source

Mucosal Immunol 2018 Nov; 11(6):1591-1605

Volume

11

Issue

6

First Page

1591

Last Page

1605

ISSN

1935-3456

PMID

30115998

DOI

https://doi.org/10.1038/s41385-018-0072-x

Grant

AI121920, NS105539, The Jackson Laboratory Director’s Innovation Fund

Abstract

Human mucosal-associated invariant T (MAIT) cell receptors (TCRs) recognize bacterial riboflavin pathway metabolites through the MHC class 1-related molecule MR1. However, it is unclear whether MAIT cells discriminate between many species of the human microbiota. To address this, we developed an in vitro functional assay through human T cells engineered for MAIT-TCRs (eMAIT-TCRs) stimulated by MR1-expressing antigen-presenting cells (APCs). We then screened 47 microbiota-associated bacterial species from different phyla for their eMAIT-TCR stimulatory capacities. Only bacterial species that encoded the riboflavin pathway were stimulatory for MAIT-TCRs. Most species that were high stimulators belonged to Bacteroidetes and Proteobacteria phyla, whereas low/non-stimulator species were primarily Actinobacteria or Firmicutes. Activation of MAIT cells by high- vs low-stimulating bacteria also correlated with the level of riboflavin they secreted or after bacterial infection of macrophages. Remarkably, we found that human T-cell subsets can also present riboflavin metabolites to MAIT cells in a MR1-restricted fashion. This T-T cell-mediated signaling also induced IFNγ, TNF and granzyme B from MAIT cells, albeit at lower level than professional APC. These findings suggest that MAIT cells can discriminate and categorize complex human microbiota through computation of TCR signals depending on antigen load and presenting cells, and fine-tune their functional responses.

Recommended Citation

Tastan C, Karhan E, Zhou W, Fleming E, Voigt A, Yao X, Wang L, Horne M, Placek L, Kozhaya L, Oh J, Unutmaz D. Tuning of human MAIT cell activation by commensal bacteria species and MR1-dependent T-cell presentation. Mucosal Immunol 2018 Nov; 11(6):1591-1605