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

Marielle C. Gold, James E. McLaren, Joseph A. Reistetter, Sue Smyk-Pearson, Kristin Ladell, Gwendolyn M. Swarbrick, Yik Y.L. Yu, Ted H. Hansen, Ole Lund, Morten Nielsen, Bram Gerritsen, Can Kesmir, John J. Miles, Deborah A. Lewinsohn, David A. Price, David M. Lewinsohn

Research output: Contribution to journalArticle

116 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1601-1610
Number of pages10
JournalJournal of Experimental Medicine
Volume211
Issue number8
DOIs
StatePublished - 2014

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Gold, M. C., McLaren, J. E., Reistetter, J. A., Smyk-Pearson, S., Ladell, K., Swarbrick, G. M., Yu, Y. Y. L., Hansen, T. H., Lund, O., Nielsen, M., Gerritsen, B., Kesmir, C., Miles, J. J., Lewinsohn, D. A., Price, D. A., & Lewinsohn, D. M. (2014). MR1-restricted MAIT cells display ligand discrimination and pathogen selectivity through distinct T cell receptor usage. Journal of Experimental Medicine, 211(8), 1601-1610. https://doi.org/10.1084/jem.20140507