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J Exp Med. 2014 Jul 28;211(8):1601-10. doi: 10.1084/jem.20140507. Epub 2014 Jul 21.

MR1-restricted MAIT cells display ligand discrimination and pathogen selectivity through distinct T cell receptor usage.

Author information

1
Division of Pulmonary and Critical Care Medicine, Department of Molecular Microbiology and Immunology, and Department of Pediatrics, Oregon Health and Science University, Portland, OR 97239Division of Pulmonary and Critical Care Medicine, Department of Molecular Microbiology and Immunology, and Department of Pediatrics, Oregon Health and Science University, Portland, OR 97239 Portland VA Medical Center, Portland, OR 97239 goldm@ohsu.edu lewinsod@ohsu.edu.
2
Institute of Infection and Immunity, Cardiff University School of Medicine, Cardiff CF14 4XN, Wales, UK.
3
Division of Pulmonary and Critical Care Medicine, Department of Molecular Microbiology and Immunology, and Department of Pediatrics, Oregon Health and Science University, Portland, OR 97239.
4
Department of Pathology and Immunology, Washington University in St. Louis School of Medicine, St. Louis, MO 63110.
5
Center for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark, 2800 Lyngby, Denmark.
6
Center for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark, 2800 Lyngby, Denmark Instituto de Investigaciones Biotecnológicas, Universidad Nacional de San Martín, 1650 San Martín, Buenos Aires, Argentina.
7
Theoretical Biology and Bioinformatics Group, Utrecht University, 3584 CH Utrecht, Netherlands.
8
Institute of Infection and Immunity, Cardiff University School of Medicine, Cardiff CF14 4XN, Wales, UK QIMR Berghofer Medical Research Institute, Brisbane, Queensland 4006, Australia.
9
Division of Pulmonary and Critical Care Medicine, Department of Molecular Microbiology and Immunology, and Department of Pediatrics, Oregon Health and Science University, Portland, OR 97239Division of Pulmonary and Critical Care Medicine, Department of Molecular Microbiology and Immunology, and Department of Pediatrics, Oregon Health and Science University, Portland, OR 97239.
10
Institute of Infection and Immunity, Cardiff University School of Medicine, Cardiff CF14 4XN, Wales, UK Human Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.

Abstract

Mucosal-associated invariant T (MAIT) cells express a semi-invariant T cell receptor (TCR) that detects microbial metabolites presented by the nonpolymorphic major histocompatibility complex (MHC)-like molecule MR1. The highly conserved nature of MR1 in conjunction with biased MAIT TCRα chain usage is widely thought to indicate limited ligand presentation and discrimination within a pattern-like recognition system. Here, we evaluated the TCR repertoire of MAIT cells responsive to three classes of microbes. Substantial diversity and heterogeneity were apparent across the functional MAIT cell repertoire as a whole, especially for TCRβ chain sequences. Moreover, different pathogen-specific responses were characterized by distinct TCR usage, both between and within individuals, suggesting that MAIT cell adaptation was a direct consequence of exposure to various exogenous MR1-restricted epitopes. In line with this interpretation, MAIT cell clones with distinct TCRs responded differentially to a riboflavin metabolite. These results suggest that MAIT cells can discriminate between pathogen-derived ligands in a clonotype-dependent manner, providing a basis for adaptive memory via recruitment of specific repertoires shaped by microbial exposure.

PMID:
25049333
PMCID:
PMC4113934
DOI:
10.1084/jem.20140507
[Indexed for MEDLINE]
Free PMC Article

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