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

Author

Gold MC, McLaren JE, Reistetter JA, Smyk-Pearson S, Ladell K, Swarbrick GM, Yu YY, Hansen TH, Lund O, Nielsen M, Gerritsen B, Kesmir C, Miles JJ, Lewinsohn DA, Price DA, and Lewinsohn DM

Subjects
Amino Acid Sequence, Bacteria drug effects, Cell Line, Clone Cells, Complementarity Determining Regions chemistry, Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor genetics, Humans, Ligands, Minor Histocompatibility Antigens, Molecular Sequence Data, Mucous Membrane drug effects, Receptors, Antigen, T-Cell, alpha-beta genetics, Sequence Homology, Amino Acid, T-Lymphocytes drug effects, Vitamin B Complex pharmacology, Antigens, Differentiation, B-Lymphocyte metabolism, Bacteria immunology, Histocompatibility Antigens Class I metabolism, Histocompatibility Antigens Class II metabolism, Mucous Membrane cytology, Mucous Membrane immunology, Receptors, Antigen, T-Cell metabolism, T-Lymphocytes metabolism
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., (© 2014 Gold et al.)

Published
2014
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2. MR1-restricted MAIT cells display ligand discrimination and pathogen selectivity through distinct T cell receptor usage

Author

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

Subjects
Receptors, Antigen, T-Cell, alpha-beta, T-Lymphocytes, Sequence Homology, Ciencias de la Salud, Complementarity determining region, Ligands, Epitope, 0302 clinical medicine, Receptors, Immunology and Allergy, Gene Rearrangement, alpha-beta, Genetics, 0303 health sciences, biology, B-Lymphocyte, Otras Ciencias de la Salud, Amino Acid, medicine.anatomical_structure, Differentiation, Antigen, Vitamin B Complex, purl.org/becyt/ford/3 [https], MAIT, CIENCIAS MÉDICAS Y DE LA SALUD, T cell, Molecular Sequence Data, Immunology, Receptors, Antigen, T-Cell, Mucosal associated invariant T cell, Major histocompatibility complex, Article, Cell Line, 03 medical and health sciences, purl.org/becyt/ford/3.3 [https], medicine, Humans, Amino Acid Sequence, Antigens, 030304 developmental biology, Mucous Membrane, Sequence Homology, Amino Acid, Bacteria, Histocompatibility Antigens Class I, T-cell receptor, Histocompatibility Antigens Class II, Gene rearrangement, T-Cell, R1, Complementarity Determining Regions, Clone Cells, Antigens, Differentiation, B-Lymphocyte, biology.protein, alpha-Chain T-Cell Antigen Receptor, T cell receptor, Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor, 030215 immunology
Abstract

MAIT cells can discriminate between pathogen-derived ligands in a clonotype-dependent manner, and the TCR repertoire is distinct within individuals, indicating that the MAIT cell repertoire is shaped by prior microbial exposure., 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.

Published
2014

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