Abstract
Two synthetic O-GlcNAc-bearing peptides that elicit H-2Db-restricted glycopeptide-specific cytotoxic T cells (CTL) have been shown to display nonreciprocal patterns of cross-reactivity. Here, we present the crystal structures of the H-2Db glycopeptide complexes to 2.85 A resolution or better. In both cases, the glycan is solvent exposed and available for direct recognition by the T cell receptor (TCR). We have modeled the complex formed between the MHC-glycopeptide complexes and their respective TCRs, showing that a single saccharide residue can be accommodated in the standard TCR-MHC geometry. The models also reveal a possible molecular basis for the observed cross-reactivity patterns of the CTL clones, which appear to be influenced by the length of the CDR3 loop and the nature of the immunizing ligand.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Acetylglucosamine / chemistry
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Acetylglucosamine / immunology
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Acetylglucosamine / metabolism
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Animals
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Clone Cells
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Crystallography, X-Ray
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Cytotoxicity, Immunologic*
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Epitopes, T-Lymphocyte / chemistry
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Glycopeptides / chemistry*
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Glycopeptides / immunology*
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H-2 Antigens / chemistry*
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H-2 Antigens / immunology
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Histocompatibility Antigen H-2D
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Humans
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Macromolecular Substances
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Mice
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Models, Molecular
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Nucleocapsid Proteins
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Nucleoproteins*
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Oligopeptides / chemistry
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Oligopeptides / immunology
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Polysaccharides / chemistry
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Receptors, Antigen, T-Cell / metabolism
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T-Lymphocytes, Cytotoxic / immunology*
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T-Lymphocytes, Cytotoxic / metabolism
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Viral Core Proteins / chemistry
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Viral Core Proteins / immunology
Substances
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Epitopes, T-Lymphocyte
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Glycopeptides
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H-2 Antigens
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Histocompatibility Antigen H-2D
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Macromolecular Substances
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Nucleocapsid Proteins
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Nucleoproteins
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Oligopeptides
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Polysaccharides
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Receptors, Antigen, T-Cell
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Viral Core Proteins
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Acetylglucosamine