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 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.
Department of Biological Sciences, University of Warwick, Coventry, UK.
K L
KL
Noakes
H T
HT
Teisserenc
J M
JM
Lord
P R
PR
Dunbar
V
V
Cerundolo
L M
LM
Roberts
D017951:Antigen Presentation; D000956:Antigens, Viral / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D001427:Bacterial Toxins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D001692:Biological Transport; D003602:Cytotoxicity, Immunologic; D004721:Endoplasmic Reticulum / Q000378:metabolism; D015395:Histocompatibility Antigens Class I; D011993:Recombinant Fusion Proteins / Q000276:immunology / Q000378:metabolism; D022622:Shiga Toxin 1; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014763:Viral Matrix Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism
D000956:Antigens, Viral; D001427:Bacterial Toxins; D015395:Histocompatibility Antigens Class I; C031540:M-protein, influenza virus; D011993:Recombinant Fusion Proteins; D022622:Shiga Toxin 1; D014763:Viral Matrix Proteins