Abstract
Mucosal-associated invariant T cells are a unique population of T cells that express a semi-invariant αβ TCR and are restricted by the MHC class I-related molecule MR1. MAIT cells recognize uncharacterized ligand(s) presented by MR1 through the cognate interaction between their TCR and MR1. To understand how the MAIT TCR recognizes MR1 at the surface of APCs cultured both with and without bacteria, we undertook extensive mutational analysis of both the MAIT TCR and MR1 molecule. We found differential contribution of particular amino acids to the MAIT TCR-MR1 interaction based upon the presence of bacteria, supporting the hypothesis that the structure of the MR1 molecules with the microbial-derived ligand(s) differs from the one with the endogenous ligand(s). Furthermore, we demonstrate that microbial-derived ligand(s) is resistant to proteinase K digestion and does not extract with common lipids, suggesting an unexpected class of antigen(s) might be recognized by this unique lymphocyte population.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antigens, Bacterial / immunology
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Antigens, Bacterial / metabolism
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B-Lymphocytes / immunology
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B-Lymphocytes / metabolism
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Cell Line
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Coculture Techniques
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Endopeptidase K / metabolism
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Escherichia coli / cytology
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Escherichia coli / immunology
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Escherichia coli / physiology*
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Histocompatibility Antigens Class I / chemistry
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Histocompatibility Antigens Class I / genetics
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Histocompatibility Antigens Class I / metabolism*
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Lipid Metabolism
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Mice
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Minor Histocompatibility Antigens
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Models, Molecular
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Mutagenesis
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Mutation
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Protein Binding
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Protein Conformation
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Proteolysis
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Receptors, Antigen, T-Cell / genetics
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Receptors, Antigen, T-Cell / metabolism
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T-Lymphocyte Subsets / cytology
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T-Lymphocyte Subsets / immunology
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T-Lymphocyte Subsets / metabolism*
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T-Lymphocyte Subsets / microbiology*
Substances
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Antigens, Bacterial
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Histocompatibility Antigens Class I
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Minor Histocompatibility Antigens
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Mr1 protein, mouse
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Receptors, Antigen, T-Cell
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Endopeptidase K