Routes J M, Bellgrau D, McGrory W J, Bautista D S, Graham F L, Cook J L
Robert W. Lisle Research Laboratory in Immunology and Tumor Cell Biology, Department of Medicine, National Jewish Center for Immunology and Respiratory Medicine, Denver, Colorado 80206.
J Virol. 1991 Mar;65(3):1450-7. doi: 10.1128/JVI.65.3.1450-1457.1991.
Virus specific, major histocompatibility complex-restricted, cytotoxic T lymphocytes (CTL) generated in Fischer strain rats infected with human adenovirus type 5 (Ad5) were found to recognize antigenic determinants encoded within the Ad5 early region 1A (E1A) gene. Preliminary mapping studies suggest that the E1A CTL epitopes are encoded within the regions between bp 625 to 810 and 916 to 974 in the first exon of this gene. These epitope-coding regions occur within subregions of E1A that are conserved functionally, and to some extent structurally (approximately 50% sequence homology), among adenoviruses of different groups. Nevertheless, Ad5-specific CTL lysed only targets infected with adenoviruses of the same group (group C; e.g., Ad2) and not targets infected with adenoviruses of different groups (groups A, B, and E). These results suggest that virus-specific CTL may limit adenoviral dissemination by destroying virus-infected cells at an early stage in the viral replicative cycle, during E1A gene expression. Expression of other adenovirus genes does not appear to be required to target infected cells for elimination by CTL.
在感染人5型腺病毒(Ad5)的Fischer品系大鼠中产生的病毒特异性、主要组织相容性复合体限制的细胞毒性T淋巴细胞(CTL),被发现可识别Ad5早期区域1A(E1A)基因内编码的抗原决定簇。初步定位研究表明,E1A CTL表位在该基因第一个外显子的625至810碱基对以及916至974碱基对之间的区域内编码。这些表位编码区域出现在E1A的功能保守且在不同程度上结构保守(约50%序列同源性)的亚区域内,这些亚区域存在于不同组的腺病毒中。然而,Ad5特异性CTL仅裂解感染同组腺病毒(C组;如Ad2)的靶细胞,而不裂解感染不同组腺病毒(A、B和E组)的靶细胞。这些结果表明,病毒特异性CTL可能通过在病毒复制周期的早期阶段,即E1A基因表达期间破坏病毒感染细胞,来限制腺病毒的传播。似乎不需要其他腺病毒基因的表达,CTL就能将感染细胞作为靶标进行清除。