Parallel T-cell cloning and deep sequencing of human MAIT cells reveal stable oligoclonal TCRβ repertoire.
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.
Experimental Immunology, Department of Biomedicine, University Hospital Basel, 4031 Basel, Switzerland.
Marco
M
Lepore
Experimental Immunology, Department of Biomedicine, University Hospital Basel, 4031 Basel, Switzerland.
Artem
A
Kalinichenko
Experimental Immunology, Department of Biomedicine, University Hospital Basel, 4031 Basel, Switzerland.
Artem
A
Kalinicenko
SIgN, Singapore Immunology Network, Agency for Science, Technology and Research, Singapore 138648, Singapore.
Alessia
A
Colone
SIgN, Singapore Immunology Network, Agency for Science, Technology and Research, Singapore 138648, Singapore.
Bhairav
B
Paleja
SIgN, Singapore Immunology Network, Agency for Science, Technology and Research, Singapore 138648, Singapore.
Amit
A
Singhal
Institute of Medical Microbiology, University of Zurich, 8006 Zurich, Switzerland.
Andreas
A
Tschumi
SIgN, Singapore Immunology Network, Agency for Science, Technology and Research, Singapore 138648, Singapore.
Bernett
B
Lee
SIgN, Singapore Immunology Network, Agency for Science, Technology and Research, Singapore 138648, Singapore.
Michael
M
Poidinger
SIgN, Singapore Immunology Network, Agency for Science, Technology and Research, Singapore 138648, Singapore.
Francesca
F
Zolezzi
Institute of Pathology, University Hospital Basel, 4031 Basel, Switzerland.
Luca
L
Quagliata
1] Institute of Medical Microbiology, University of Zurich, 8006 Zurich, Switzerland [2] National Centre for Mycobacteria, Gloriastrasse 30/32, 8006 Zurich, Switzerland.
Peter
P
Sander
SIgN, Singapore Immunology Network, Agency for Science, Technology and Research, Singapore 138648, Singapore.
Evan
E
Newell
Emerging Infectious Diseases, Duke-NUS Graduate Medical School, Singapore 169857, Singapore.
Antonio
A
Bertoletti
Institute of Pathology, University Hospital Basel, 4031 Basel, Switzerland.
Luigi
L
Terracciano
1] Experimental Immunology, Department of Biomedicine, University Hospital Basel, 4031 Basel, Switzerland [2] SIgN, Singapore Immunology Network, Agency for Science, Technology and Research, Singapore 138648, Singapore.
Gennaro
G
De Libero
1] Experimental Immunology, Department of Biomedicine, University Hospital Basel, 4031 Basel, Switzerland [2] SIgN, Singapore Immunology Network, Agency for Science, Technology and Research, Singapore 138648, Singapore.
Lucia
L
Mori
D000328:Adult; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D019673:Genes, T-Cell Receptor alpha / Q000235:genetics*; D019674:Genes, T-Cell Receptor beta / Q000235:genetics*; D006801:Humans; D012333:RNA, Messenger / Q000378:metabolism*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism*; D020539:Sequence Analysis, Protein; D016176:T-Lymphocyte Subsets / Q000378:metabolism*; D013601:T-Lymphocytes / Q000378:metabolism; D055815:Young Adult
D012333:RNA, Messenger; D016693:Receptors, Antigen, T-Cell, alpha-beta