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Exploiting retrograde transport of Shiga‐like toxin 1 for the delivery of exogenous antigens into the MHC class I presentation pathway
Author(s) -
Noakes Karen L.,
Teisserenc Hélène T.,
Lord J.Michael,
Dunbar P.Rod,
Cerundolo Vincenzo,
Roberts Lynne M.
Publication year - 1999
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(99)00609-2
Subject(s) - mhc class i , cytotoxic t cell , antigen presentation , major histocompatibility complex , transporter associated with antigen processing , biology , antigen processing , endocytosis , endoplasmic reticulum , microbiology and biotechnology , antigen , shiga toxin , virology , escherichia coli , cell , biochemistry , immunology , gene , in vitro
Shiga‐like toxin 1 (SLT) from Escherichia coli 0157: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.