Abstract
Shiga-like toxin 1 (SLT) from Escherichia coli O157:H7 enters mammalian cells by endocytosis from the cell surface to the endoplasmic reticulum before translocating into the cytosol. Here, SLT was engineered at its N- or C-terminus to carry a peptide derived from influenza virus Matrix protein for delivery to major histocompatibility complex (MHC) class I molecules. We show that SLT N-Ma was capable of sensitising cells for lysis by appropriate cytotoxic T-lymphocytes whilst no killing of SLT-resistant cells was observed. Our results demonstrate that peptide was liberated intracellularly and that retrograde transport of a disarmed cytotoxic protein can intersect the MHC class 1 presentation pathway.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antigen Presentation*
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Antigens, Viral / genetics
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Antigens, Viral / immunology
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Antigens, Viral / metabolism*
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Bacterial Toxins / genetics
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Bacterial Toxins / immunology*
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Bacterial Toxins / metabolism
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Biological Transport
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Cytotoxicity, Immunologic
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Endoplasmic Reticulum / metabolism
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Histocompatibility Antigens Class I*
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Recombinant Fusion Proteins / immunology
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Recombinant Fusion Proteins / metabolism
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Shiga Toxin 1
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T-Lymphocytes, Cytotoxic / immunology
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Viral Matrix Proteins / genetics
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Viral Matrix Proteins / immunology*
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Viral Matrix Proteins / metabolism
Substances
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Antigens, Viral
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Bacterial Toxins
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Histocompatibility Antigens Class I
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M-protein, influenza virus
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Recombinant Fusion Proteins
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Shiga Toxin 1
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Viral Matrix Proteins