IMMUNOLOGICAL RECOGNITION OF INFLUENZA VIRUS-INFECTED CELLS .2. EXPRESSION OF INFLUENZA A MATRIX PROTEIN ON INFECTED CELL-SURFACE AND ITS ROLE IN RECOGNITION BY CROSS-REACTIVE CYTOTOXIC-T CELLS
IMMUNOLOGICAL RECOGNITION OF INFLUENZA VIRUS-INFECTED CELLS .2. EXPRESSION OF INFLUENZA A MATRIX PROTEIN ON INFECTED CELL-SURFACE AND ITS ROLE IN RECOGNITION BY CROSS-REACTIVE CYTOTOXIC-T CELLS
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DOI：
10.1084/jem.146.3.673
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发表时间：
1977-01-01
影响因子：
15.3
通讯作者：
BRACIALE, TJ
中科院分区：
文献类型：
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作者：
BRACIALE, TJ
细胞毒性 T [thumus 衍生] 细胞的独特亚群 (2) 是在小鼠对 A 型流感病毒的初次或继发反应中产生的。一个亚群对免疫病毒株具有特异性。另一个亚群对不同亚型的异源 A 型病毒表现出高度的交叉反应性。本报告探讨了受感染细胞表面表达的不同流感病毒抗原被流感特异性细胞毒性 T 细胞的不同亚群识别的可能性。所提供的数据表明甲型流感基质蛋白（一种内部病毒颗粒抗原）在感染不同亚型甲型流感病毒的表面靶细胞上是可检测到的。由于这种病毒抗原是类型特异性的，即在所有 A 型流感病毒之间具有血清学交叉反应，因此它可以作为交叉反应细胞毒性 T 细胞的靶标。为了进一步检查2种细胞毒性T细胞亚群的特异性，使用糖蛋白合成抑制剂-2-脱氧-D-葡萄糖2-DG进行实验。这些实验首先检查 2-DG 对受感染细胞表面流感基质蛋白和病毒糖蛋白表达的影响，其次检查 2-DG 处理的靶细胞对细胞毒性 T 细胞裂解的敏感性。 2-DG 抑制细胞表面病毒血凝素糖蛋白的表达，但不抑制非糖基化基质蛋白的表达。此外，抑制受感染靶细胞中的糖蛋白合成会消除受感染靶细胞对病毒株特异性但不交叉反应的细胞毒性T细胞裂解的反应性。这些发现表明，流感糖蛋白（血凝素和/或神经氨酸酶）和非糖基化基质蛋白分别是病毒株特异性和交叉反应性细胞毒性 T 细胞的靶标。根据流感病毒结构和流感感染生物学的现有信息以及病毒感染细胞的细胞毒性 T 细胞识别的当前模型对这些结果进行了讨论。
Distinct subpopulations (2) of cytotoxic T [thumus-derived] cells are generated in the primary or secondary response of mice to mice to type A influenza viruses. One subpopulation is specific for the immunizing virus strain. The other subpopulation shows a high degree of cross-reactivity for heterologous type A virus of a different subtype. This report examines the possibility that distinct influenxa virus antigens, expressed on the surface of the infected cell, are recognized by the different subpopulations of influenza-specific cytotoxic T cells. Data are presented which demonstrate that influenza A matrix protein, an internal virion antigen, is detectable on the surface target cells infected with influenza A viruses of different subtypes. Since this viral antigen is type specific, i.e., serologically cross-reactive among all type A influenza viruses, it could serve as the target for cross-reactive cytotoxic T cells. To further examine the specificity of the 2 cytotoxic T-cell subpopulations, experiments were carried out by using the inhibitor of glycoprotein synthesis - 2-Deoxy-D-Glucose 2-DG. These experiments examine first the effect of 2-DG on the expression of influenza matrix protein and viral glycoprotein on the infected cell surface and second, the susceptibility of 2-DG-treated target cells to lysis by cytotoxic T cells. 2-DG inhibits the expression of the viral hemagglutinin glycoprotein on the cell surface but does not inhibit the expression of the nonglycosylated matrix protein. Furthermore, inhibition of glycoprotein synthesis in infected target cells abrogates the reactivity of infected target cells to lysis by virus strain-specific but not cross-reactive cytotoxic T cells. These findings suggest that the influenza glycoproteins (hemagglutinin and/or neuraminidase) and the nonglycosylated matrix protein are the targets for the virus strain-specific and cross-reactive cytotoxic T cells, respectively. These results are discussed in the light of available information on influenza virus structure and the biology of influenza infection and in terms of current models for cytotoxic T-cell recognition of virus-infected cells.