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利用志贺样毒素1的逆向运输将外源性抗原递送至MHC I类呈递途径。

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

作者信息

Noakes K L, Teisserenc H T, Lord J M, Dunbar P R, Cerundolo V, Roberts L M

机构信息

Department of Biological Sciences, University of Warwick, Coventry, UK.

出版信息

FEBS Lett. 1999 Jun 18;453(1-2):95-9. doi: 10.1016/s0014-5793(99)00609-2.

DOI:10.1016/s0014-5793(99)00609-2
PMID:10403383
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.

摘要

来自大肠杆菌O157:H7的志贺样毒素1(SLT)通过内吞作用从细胞表面进入哺乳动物细胞,直至内质网,然后转移至细胞质中。在此,我们对SLT的N端或C端进行改造,使其携带一段源自流感病毒基质蛋白的肽段,以便递送至主要组织相容性复合体(MHC)I类分子。我们发现,SLT N-Ma能够使细胞对相应的细胞毒性T淋巴细胞的裂解作用敏感,而对SLT抗性细胞则未观察到杀伤作用。我们的结果表明,肽段在细胞内被释放,并且一种失活的细胞毒性蛋白的逆向转运能够与MHC I类呈递途径相交。

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