TY - JOUR
T1 - MR1-restricted MAIT cells display ligand discrimination and pathogen selectivity through distinct T cell receptor usage
AU - Gold, Marielle C.
AU - McLaren, James E.
AU - Reistetter, Joseph A.
AU - Smyk-Pearson, Sue
AU - Ladell, Kristin
AU - Swarbrick, Gwendolyn M.
AU - Yu, Yik Y.L.
AU - Hansen, Ted H.
AU - Lund, Ole
AU - Nielsen, Morten
AU - Gerritsen, Bram
AU - Kesmir, Can
AU - Miles, John J.
AU - Lewinsohn, Deborah A.
AU - Price, David A.
AU - Lewinsohn, David M.
PY - 2014
Y1 - 2014
N2 - 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.
AB - 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.
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U2 - 10.1084/jem.20140507
DO - 10.1084/jem.20140507
M3 - Article
C2 - 25049333
AN - SCOPUS:84905118556
SN - 0022-1007
VL - 211
SP - 1601
EP - 1610
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
IS - 8
ER -