Exploiting retrograde transport of Shiga-like toxin 1 for the delivery of exogenous antigens into the MHC class I presentation pathway

Shiga-like toxin 1 (SLT) from Escherichia coli 0157:H7 enters mammalian cel ls by endocytosis from the cell surface to the endoplasmic reticulum before translocating into the cytosol. Here, SLT mas engineered at its N- or C-te rminus to carry a peptide derived from influenza virus Matrix protein for d elivery to major histocompatibility complex (MHC) class I molecules, We sho w that SLT N-Ma was capable of sensitising cells for lysis by appropriate c ytotoxic T-lymphocytes whilst no killing of SLT-resistant cells was observe d. Our results demonstrate that peptide was liberated intracellularly and t hat retrograde transport of a disarmed cytotoxic protein can intersect the MHC class 1 presentation pathway. (C) 1999 Federation of European Biochemic al Societies.