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, Deborah A. Lewinsohn, David A. Price, David M. Lewinsohn

    Research output: Contribution to journalConference abstract in journalResearchpeer-review

    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
    JournalMolecular Immunology
    Volume68
    Issue number2, Part A
    Pages (from-to)134-134
    ISSN0161-5890
    DOIs
    Publication statusPublished - 2015
    EventThe 8th International Workshop on Antigen Processing and Presentation - Philadelphia, PA, United States
    Duration: 10 Jun 201413 Jun 2014
    Conference number: 8

    Conference

    ConferenceThe 8th International Workshop on Antigen Processing and Presentation
    Number8
    CountryUnited States
    CityPhiladelphia, PA
    Period10/06/201413/06/2014

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