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淋巴细胞性脉络丛脑膜炎病毒核蛋白的主要组织相容性复合体依赖性T细胞表位及其对病毒性疾病的保护能力

Major histocompatibility complex--dependent T cell epitopes of lymphocytic choriomeningitis virus nucleoprotein and their protective capacity against viral disease.

作者信息

Schulz M, Aichele P, Vollenweider M, Bobe F W, Cardinaux F, Hengartner H, Zinkernagel R M

机构信息

Institute of Pathology, University Hospital, Zürich, Switzerland.

出版信息

Eur J Immunol. 1989 Sep;19(9):1657-67. doi: 10.1002/eji.1830190921.

DOI:10.1002/eji.1830190921
PMID:2477254
Abstract

In mice the immune response to infection with lymphocytic choriomeningitis virus (LCMV), a member of the arenavirus family, is mainly based on the activity of cytotoxic T cells. The immunogenic epitopes of the viral nucleoprotein recognized by cytotoxic T cells in various inbred strains of mice were defined. These epitopes were located in H-2d and H-2q mice in the amino-terminal region and in H-2b mice in the carboxy-terminal region of the nucleoprotein. A detailed analysis with synthetic peptides allowed the definition of a common epitope of 9 amino acids in H-2d and H-2q mice and of about 15 amino acids in H-2b mice. These T cell epitopes were all recognized in association with H-2 D or L transplantation antigen. The protective capacity of recombinant vaccinia viruses expressing these epitopes was documented by assaying prevention of virus replication, protection against LCM and prevention of the local footpad swelling reaction. Thus, distinct T cell epitopes on the same internal viral protein mediate protection in a major histocompatibility complex-restricted manner.

摘要

在小鼠中,对沙粒病毒科成员淋巴细胞性脉络丛脑膜炎病毒(LCMV)感染的免疫反应主要基于细胞毒性T细胞的活性。确定了细胞毒性T细胞在各种近交系小鼠中识别的病毒核蛋白的免疫原性表位。这些表位位于核蛋白氨基末端区域的H-2d和H-2q小鼠中,以及位于核蛋白羧基末端区域的H-2b小鼠中。用合成肽进行的详细分析确定了H-2d和H-2q小鼠中一个9个氨基酸的共同表位以及H-2b小鼠中约15个氨基酸的共同表位。这些T细胞表位均与H-2 D或L移植抗原相关联而被识别。通过检测病毒复制的预防、对LCM的保护以及局部足垫肿胀反应的预防,证明了表达这些表位的重组痘苗病毒的保护能力。因此,同一病毒内部蛋白上不同的T细胞表位以主要组织相容性复合体限制的方式介导保护作用。

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