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

FEBS Letters

Dunbar, P.Rod²  Teisserenc, Hélène T.²  Cerundolo, Vincenzo²  Noakes, Karen L.¹  Roberts, Lynne M.¹  Lord, J.Michael¹ 

[1] Department of Biological Sciences, University of Warwick, Coventry CV4 7AL, UK;Molecular Immunology Group, Institute of Molecular Medicine, Nuffield Department of Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DS, UK

关键词: Influenza Matrix protein;    Shiga-like toxin A chain;    Endoplasmic reticulum;    BFA;    brefeldin A;    LF;    anthrax toxin lethal factor;    CTL;    cytotoxic T lymphocytes;    DT;    diphtheria toxin;    ER;    endoplasmic reticulum;    IFN-γ;    interferon gamma;    MHC;    major histocompatibility complex;    PE;    Pseudomonas exotoxin A;    SLT;    Shiga-like toxin 1;   

DOI  :  10.1016/S0014-5793(99)00609-2

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown