Functionally diverse human T cells recognize non-microbial antigens presented by MR1
- University of Basel, Switzerland
- A*STAR, Singapore
- University Hospital Basel, Switzerland
Abstract
MHC class I-related molecule MR1 presents riboflavin- and folate-related metabolites to mucosal-associated invariant T cells, but it is unknown whether MR1 can present alternative antigens to other T cell lineages. In healthy individuals we identified MR1-restricted T cells (named MR1T cells) displaying diverse TCRs and reacting to MR1-expressing cells in the absence of microbial ligands. Analysis of MR1T cell clones revealed specificity for distinct cell-derived antigens and alternative transcriptional strategies for metabolic programming, cell cycle control and functional polarization following antigen stimulation. Phenotypical and functional characterization of MR1T cell clones showed multiple chemokine receptor expression profiles and secretion of diverse effector molecules, suggesting functional heterogeneity. Accordingly, MR1T cells exhibited distinct T helper-like capacities upon MR1-dependent recognition of target cells expressing physiological levels of surface MR1. These data extend the role of MR1 beyond microbial antigen presentation and indicate MR1T cells are a normal part of the human T cell repertoire.
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Funding
Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (310030-149571)
- Gennaro De Libero
European Commission (643381)
- Gennaro De Libero
Science and Engineering Research Council (1121480006)
- Gennaro De Libero
Universität Basel (Core Funding)
- Gennaro De Libero
Agency for Science, Technology and Research (1201826277)
- Gennaro De Libero
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Human subjects: Venous blood was taken from healthy donors after informed consent obtained at the time of blood collection under approval of the "Ethikkommision Nordwest und Zentralschweiz/EKNZ (139/13).
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© 2017, Lepore et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Functionally diverse human T cells recognize non-microbial antigens presented by MR1
eLife 6:e24476.
https://doi.org/10.7554/eLife.24476
