Parallel T-cell cloning and deep sequencing of human MAIT cells reveal stable oligoclonal TCRβ repertoire

Marco Lepore, Artem Kalinichenko, Alessia Colone, Bhairav Paleja, Amit Singhal, Andreas Tschumi, Bernett Lee, Michael Poidinger, Francesca Zolezzi, Luca Quagliata, Peter Sander, Evan Newell, Antonio Bertoletti, Luigi Terracciano, Gennaro De Libero () and Lucia Mori ()
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Marco Lepore: Experimental Immunology, University Hospital Basel
Artem Kalinichenko: Experimental Immunology, University Hospital Basel
Alessia Colone: SIgN, Singapore Immunology Network, Agency for Science, Technology and Research
Bhairav Paleja: SIgN, Singapore Immunology Network, Agency for Science, Technology and Research
Amit Singhal: SIgN, Singapore Immunology Network, Agency for Science, Technology and Research
Andreas Tschumi: Institute of Medical Microbiology, University of Zurich
Bernett Lee: SIgN, Singapore Immunology Network, Agency for Science, Technology and Research
Michael Poidinger: SIgN, Singapore Immunology Network, Agency for Science, Technology and Research
Francesca Zolezzi: SIgN, Singapore Immunology Network, Agency for Science, Technology and Research
Luca Quagliata: Institute of Pathology, University Hospital Basel
Peter Sander: Institute of Medical Microbiology, University of Zurich
Evan Newell: SIgN, Singapore Immunology Network, Agency for Science, Technology and Research
Antonio Bertoletti: Emerging Infectious Diseases, Duke-NUS Graduate Medical School
Luigi Terracciano: Institute of Pathology, University Hospital Basel
Gennaro De Libero: Experimental Immunology, University Hospital Basel
Lucia Mori: Experimental Immunology, University Hospital Basel

Nature Communications, 2014, vol. 5, issue 1, 1-15

Abstract: Abstract Mucosal-associated invariant T (MAIT) cells are abundant in humans and recognize conserved bacterial antigens derived from riboflavin precursors, presented by the non-polymorphic MHC class I-like molecule MR1. Here we show that human MAIT cells are remarkably oligoclonal in both the blood and liver, display high inter-individual homology and exhibit a restricted length CDR3β domain of the TCRVβ chain. We extend this analysis to a second sub-population of MAIT cells expressing a semi-invariant TCR conserved between individuals. Similar to ‘conventional’ MAIT cells, these lymphocytes react to riboflavin-synthesizing microbes in an MR1-restricted manner and infiltrate solid tissues. Both MAIT cell types release Th0, Th1 and Th2 cytokines, and sCD40L in response to bacterial infection, show cytotoxic capacity against infected cells and promote killing of intracellular bacteria, thus suggesting important protective and immunoregulatory functions of these lymphocytes.

Date: 2014
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DOI: 10.1038/ncomms4866

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