DIFFERENT PATTERNS OF EPSTEIN-BARR VIRUS GENE-EXPRESSION AND OF CYTO-TOXIC T-CELL RECOGNITION IN B-CELL LINES INFECTED WITH TRANSFORMING (B95.8) OR NONTRANSFORMING (P3HR1) VIRUS-STRAINS
DIFFERENT PATTERNS OF EPSTEIN-BARR VIRUS GENE-EXPRESSION AND OF CYTO-TOXIC T-CELL RECOGNITION IN B-CELL LINES INFECTED WITH TRANSFORMING (B95.8) OR NONTRANSFORMING (P3HR1) VIRUS-STRAINS
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DOI：
10.1128/jvi.62.3.894-901.1988
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发表时间：
1988-03-01
影响因子：
5.4
通讯作者：
RICKINSON, AB
中科院分区：
文献类型：
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作者：
MURRAY, RJ;YOUNG, LS;RICKINSON, AB
EB病毒（EBV）阴性伯基特淋巴瘤（BL）细胞系已通过体外感染转化EBV株B95.8和非转化突变株P3 HR 1（其编码核抗原EBNA 2的基因缺失）转化为EBV基因组阳性。已经比较了这些B95.8-和P3 HR 1-转化的株系的EBV潜伏基因的表达模式（即，这些病毒基因在正常B细胞来源的所有EBV转化系中组成型表达），并被EBV特异性细胞毒性T淋巴细胞（CTL）识别，以鉴定哪些潜伏基因产物为T细胞应答提供靶抗原。在几种不同的EBV阴性BL细胞背景上的B95.8转化株均显示可检测到核抗原EBNA 1、EBNA 2和EBNA 3以及潜伏膜蛋白（LMP）的表达;这种转化也被EBV特异性CTL制备物清楚地识别，其通过靶细胞表面上选择的人类白细胞抗原（HLA）I类抗原进行限制。相应的P3 HR 1转化系（缺乏EBNA 2基因）表达EBNA 1和EBNA 3，但令人惊讶的是，没有显示出可检测的LMP;此外，这些转化不被EBV特异性CTL识别。T细胞识别的这种差异不是由于两种类型转换之间相关HLA限制性决定簇表达的任何差异，如特异性单克隆抗体的结合以及B95.8和P3 HR 1转换对针对这些相同HLA分子的同种特异性CTL的易感性所示。结果表明，在正常感染周期中，EBNA 2可能是LMP后续表达所需的，并且EBNA 2和LMP（但EBNA 1或EBNA 3除外）可能为EB病毒特异性T细胞反应提供靶抗原。
Epstein-Barr virus (EBV)-negative Burkitt''s lymphoma (BL) cell lines have been converted to EBV genome positivity by in vitro infection with the transforming EBV strain B95.8 and with the nontransforming mutant strain P3HR1, which has a deletion in the gene encoding the nuclear antigen EBNA2. These B95.8- and P3HR1-converted lines have been compared for their patterns of expression of EBV latent genes (i.e., those viral genes constitutively expressed in all EBV-transformed lines of normal B-cell origin) and for their recognition by EBV-specific cytotoxic T lymphocytes (CTLs), in an effort to identify which latent gene products provide target antigens for the T-cell response. B95.8-converted lines on several different EBV-negative BL-cell backgrounds all showed detectable expression of the nuclear antigens EBNA1, EBNA2, and EBNA3 and of the latent membrane protein(LMP); such converts were also clearly recognized by EBV-specific CTL preparations with restriction through selected human leukocyte antigen (HLA) class I antigens on the target cell surface. The corresponding P3HR1-converted lines (lacking an EBNA2 gene) expressed EBNA1 and EBNA3 but, surprisingly, showed no detectable LMP; furthermore, these converts were not recognized by EBV-specific CTLs. Such differences in T-cell recognition were not due to any differences in expression of the relevant HLA-restricting determinants between the two types of convert, as shown by binding of specific monoclonal antibodies and by the susceptibility of both B95.8 and P3HR1 converts to allospecific CTLs directed against these same HLA molecules. The results suggest that in the normal infectious cycle, EBNA2 may be required for subsequent expression of LMP and that both EBNA2 and LMP (but not EBNA1 or EBNA3) may provide target antigens for the EBV-specific T-cell response.