Targeted delivery of peptide epitopes to class I major histocompatibility molecules by a modified Pseudomonas exotoxin.
Targeted delivery of peptide epitopes to class I major histocompatibility molecules by a modified Pseudomonas exotoxin.
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通过修饰的假单胞菌外毒素将肽表位靶向递送至 I 类主要组织相容性分子。
DOI：
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发表时间：
1993
影响因子：
11.1
通讯作者：
Margaret A. Liu
中科院分区：
文献类型：
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作者：
John J. Donnelly;Jeffrey B. Ulmer;Linda A. Hawe;A. Friedman;Xiao;Karen R. Leander;J. Shiver;Allen Oliff;Douglas Martinez;Donna L. Montgomery;Margaret A. Liu
表达 CD8 表面标记的细胞毒性 T 淋巴细胞 (CTL) 识别与主要组织相容性复合物 (MHC) I 类分子相关的肽。尽管大多数在 MHC I 类分子上表达的肽源自自身或病毒编码的蛋白质，但将外源蛋白质递送至胞质溶胶可导致它们被加工以呈递给 MHC I 类分子上的 CTL。我们描述了两种融合蛋白（PEMa 和 PENP），由假单胞菌外毒素 A (PE) 的结合和易位结构域组成，分别与甲型流感基质蛋白和核蛋白的肽表位融合。这些融合蛋白被 MHC I 类阳性靶细胞内化和加工，导致靶细胞对肽特异性 CTL 裂解敏感。已知会干扰野生型 PE 中毒的点突变也会降低 PEMa 使靶细胞敏感的能力。肽或多肽表位与 PE 的融合提供了一种在不使用自我复制剂的情况下引发 CTL 的潜在方法，以及用于研究 MHC I 类限制性抗原加工的有用探针。
Cytotoxic T lymphocytes (CTLs) expressing the CD8 surface marker recognize peptides in association with major histocompatibility complex (MHC) class I molecules. Although most peptides expressed on MHC class I molecules are derived from self- or virally encoded proteins, delivery of exogenous proteins to the cytosol can result in their being processed for presentation to CTLs on MHC class I molecules. We describe two fusion proteins (PEMa and PENP), consisting of the binding and translocating domains of Pseudomonas exotoxin A (PE), fused to peptide epitopes from influenza A matrix protein and nucleoprotein, respectively. These fusion proteins were internalized and processed by MHC class I-positive target cells, resulting in sensitization of target cells for lysis by peptide-specific CTLs. A point mutation known to interfere with intoxication by wild-type PE also reduced the ability of PEMa to sensitize target cells. Fusion of peptide or polypeptide epitopes with PE provides a potential means of eliciting CTLs without the use of self-replicating agents, as well as a useful probe for studying MHC class I-restricted antigen processing.