The early expression of glycoprotein B from herpes simplex virus can be detected by antigen-specific CD8+ T cells

The early expression of glycoprotein B from herpes simplex virus can be detected by antigen-specific CD8+ T cells
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DOI:
10.1128/jvi.77.4.2445-2451.2003
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发表时间:
2003-02-01
影响因子:
5.4
通讯作者:
Carbone, FR
Carbone, FR
中科院分区:
医学2区
文献类型:
--
作者:
Mueller, SN;Jones, CM;Carbone, FR

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对皮肤单纯疱疹病毒I型(HSV-1)感染的免疫应答以显著的快速开始。特异性细胞毒性T淋巴细胞(CTL)的激活在感染后数小时内开始,即使引流淋巴结内的反应在近5天后达到峰值。HSV基因产物根据其动力学和表达要求分为三个主要组,α、β和γ。在C57 BL/6小鼠中,来自HSV的免疫显性表位来源于糖蛋白B(gB(498-505))。虽然gB被认为是一种γ或“晚期”基因产物,但以前的报道表明,感染后不久可能会发生某种程度的基因表达。使用布雷菲德菌素A作为病毒抗原呈递给主要组织相容性复合体I类限制性CTL的特异性抑制剂,我们已经正式解决了感染后免疫相关方式中gB肽表达的时间。通过T细胞活化检测的gB肽的呈递在感染后2小时内首次观察到。与另一种病毒表位表达的感染早期,HSV-1核糖核苷酸还原酶,比较表明,gB提出了与这个经典的早期基因产物相同的动力学。此外,通过在小鼠HSV-1感染后体内快速引发初始转基因CD 8(+)T细胞,进一步说明了gB表达的这种快速性。这些结果证实,gB在HSV-1感染后迅速表达,其水平能够有效刺激CD 8(+)T细胞。
The immune response to cutaneous herpes simplex virus type I (HSV-1) infection begins with remarkable rapidity. Activation of specific cytotoxic T lymphocytes (CTL) begins within hours of infection, even though the response within the draining lymph nodes peaks nearly 5 days later. HSV gene products are classified into three main groups, alpha, beta, and gamma, based on their kinetics and requirements for expression. In C57BL/6 mice, the immunodominant epitope from HSV is derived from glycoprotein B (gB(498-505)). While gB is considered a gamma or "late" gene product, previous reports have indicated that some level of gene expression may occur soon after infection. Using brefeldin A as a specific inhibitor of viral antigen presentation to major histocompatibility complex class I-restricted CTL, we have formally addressed the timing of gB peptide expression in an immunologically relevant manner following infection. Presentation of gB peptide detected by T-cell activation was first observed within 2 h of infection. Comparison with another viral epitope expressed early during infection, HSV-1 ribonucleotide reductase, demonstrated that gB is presented with the same kinetics as this classical early-gene product. Moreover, this rapidity of gB expression was further illustrated via rapid priming of naive transgenic CD8(+) T cells in vivo after HSV-1 infection of mice. These results establish that gB is expressed rapidly following HSV-1 infection, at levels capable of effectively stimulating CD8(+) T cells.