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将抗原脂质体修饰靶细胞作为一种改变其对细胞毒性T淋巴细胞裂解敏感性的方法。

Antigen-liposome modification of target cells as a method to alter their susceptibility to lysis by cytotoxic T lymphocytes.

作者信息

Hale A H, Ruebush M J, Lyles D S, Harris D T

出版信息

Proc Natl Acad Sci U S A. 1980 Oct;77(10):6105-8. doi: 10.1073/pnas.77.10.6105.

Abstract

A method of liposome modification of cell surfaces to render unsuitable target cells susceptible to lysis by anti-viral cytotoxic T lymphocytes (CTLs) is described. Liposomes containing the hemagglutinin-neuraminidase (HN) and fusion (F) glycoproteins of Sendai virus as well as purified H-2Kk cells and rendering those cells susceptible to lysis by B10. A anti-Sendai virus or anti-H-2Kk CTLs. The absence from the modifying liposomes of the HN or F proteins or H-2Kk antigens eliminated the ability of the target cells to be recognized and lysed by either effector cell population. Vesicles containing HN, H-2Kk molecules, and inactive fusion protein (Fo) were not capable of increasing the susceptibility of h-2-negative target cells to lysis. Liposomes containing inactive fusion protein were similarly unable to render H-2-positive target cells susceptible to lysis by anti-Sendai virus CTLs, suggesting that fusion of the liposomes to the cell surface is a prerequisite to lysis. It did not appear that attachement of liposomes to the cell surface was sufficient for generation of susceptible targets, however, because attachment to the cell surface was observed, as long as the HN glycoprotein was present in the liposomes. These results indicate that purified H-2Kk glycoproteins are target antigens for anti-H-2k CTLs and that B10 . A anti-Sendai virus CTLs recognize in an H-2-restricted manner the HN, F, or both glycoproteins of Sendai virus in the context of the purified H-2Kk glycoproteins. This technique of liposome modification of cell surfaces has potential applications in the examination of CTL antigen recognition and immunotherapy of many viral and neoplastic diseases.

摘要

描述了一种对细胞表面进行脂质体修饰的方法,以使不合适的靶细胞易于被抗病毒细胞毒性T淋巴细胞(CTL)裂解。含有仙台病毒血凝素神经氨酸酶(HN)和融合(F)糖蛋白的脂质体,以及纯化的H-2Kk细胞,并使这些细胞易于被B10.A抗仙台病毒或抗H-2Kk CTL裂解。修饰脂质体中不存在HN或F蛋白或H-2Kk抗原消除了靶细胞被任一效应细胞群体识别和裂解的能力。含有HN、H-2Kk分子和无活性融合蛋白(Fo)的囊泡不能增加h-2阴性靶细胞对裂解的敏感性。含有无活性融合蛋白的脂质体同样不能使H-2阳性靶细胞易于被抗仙台病毒CTL裂解,这表明脂质体与细胞表面的融合是裂解的先决条件。然而,似乎脂质体与细胞表面的附着不足以产生敏感靶细胞,因为只要脂质体中存在HN糖蛋白,就观察到其与细胞表面的附着。这些结果表明,纯化的H-2Kk糖蛋白是抗H-2k CTL的靶抗原,并且B10.A抗仙台病毒CTL在纯化的H-2Kk糖蛋白的背景下以H-2限制性方式识别仙台病毒的HN、F或两者糖蛋白。这种细胞表面脂质体修饰技术在CTL抗原识别检查和许多病毒及肿瘤疾病的免疫治疗中具有潜在应用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/989e/350222/63414cf6c8a7/pnas00497-0567-a.jpg

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