CDS CTL from genital herpes simplex lesions: Recognition of viral tegument and immediate early proteins and lysis of infected cutaneous cells
CDS CTL from genital herpes simplex lesions: Recognition of viral tegument and immediate early proteins and lysis of infected cutaneous cells
复制标题
DOI：
10.4049/jimmunol.166.6.4049
复制
发表时间：
2001-03-15
影响因子：
4.4
通讯作者：
Corey, L
中科院分区：
文献类型：
--
作者：
Koelle, DM;Chen, HBB;Corey, L
HSV-2引起慢性感染，CD 8 CTL可以发挥几种保护作用，并且刺激CD 8应答是针对该病原体的疫苗设计的合理要素。由CD 8 T细胞识别的病毒Ag在很大程度上是未知的。据推测，TAP的HSV抑制可能有利于病毒体输入蛋白或病毒立即早期蛋白的识别。我们使用从生殖器HSV-2病变获得的HSV特异性CD 8 CTL克隆来测试这种预测。药物和复制阻断实验与上述病毒蛋白类的特异性一致。使用病毒DNA的分子文库通过表达克隆确定精细特异性，并鉴定在纳摩尔浓度下识别的肽表位。4个克隆中有3个能识别由UL 47和UL 49基因编码的病毒被膜蛋白。被膜Ag衍生表位的加工是TAP依赖性的。表皮特异性CTL能够在短时间感染后溶解适合HLA I类的成纤维细胞。角质形成细胞的裂解需要更长时间的感染和用IFN-γ预处理。另一个克隆识别立即早期蛋白ICP 0。对这些病变定义的表位特异的淋巴细胞可以从另外的受试者的PBMC中再活化。这些数据与HSV免疫逃避基因对病变中CD 8 CTL识别的蛋白质选择的影响一致。被膜蛋白首次被鉴定为HSV特异性CD 8 CTL识别的抗原，是理想的候选疫苗化合物。
HSV-2 causes chronic infections, CDS CTL may play several protective roles, and stimulation of a CD8 response is a rational element of vaccine design for this pathogen, The viral Ags recognized by CD8 T cells are largely unknown. It has been hypothesized that HSV inhibition of TAP may favor recognition of virion input proteins or viral immediate early proteins. We tested this prediction using HSV-specific CD8 CTL clones obtained from genital HSV-2 lesions. Drug and replication block experiments were consistent with specificity for the above-named classes of viral proteins, Fine specificity was determined by expression cloning using molecular libraries of viral DNA, and peptide epitopes recognized at nanomolar concentrations were identified. Three of four clones recognized the viral tegument proteins encoded by genes UL47 and UL49, These proteins are transferred into the cytoplasm on virus entry. Processing of the tegument Ag-derived epitopes was TAP dependent. The tegument-specific CTL were able to lyse HLA class I-appropriate fibroblasts after short times of infection. Lysis of keratinocytes required longer infection and pretreatment with IFN-gamma, Another clone recognized an immediate early protein, ICP0, Lymphocytes specific for these lesion-defined epitopes could be reactivated from the PBMC of additional subjects. These data are consistent with an influence of HSV immune evasion genes upon the selection of proteins recognized by CD8 CTL in lesions. Tegument proteins, identified for the first time as Ags recognized by HSV-specific CD8 CTL, are rational candidate vaccine compounds.