Comerford S A, McCance D J, Dougan G, Tite J P
Department of Molecular Biology, Wellcome Research Laboratories, Beckenham, Kent, United Kingdom.
J Virol. 1991 Sep;65(9):4681-90. doi: 10.1128/JVI.65.9.4681-4690.1991.
There is strong evidence implicating human papillomavirus type 16 (HPV16) in the genesis of human genital cancer. Viral DNA has been identified in invasive carcinoma of the uterine cervix and in cell lines derived from cervical carcinomas. These sequences are actively transcribed, and translation products corresponding to the early (E)-region genes have been identified. The most abundant viral protein is the E7 protein, which has been shown to possess transforming activity for both established and primary cells. In addition, it has been shown to bind to a cellular tumor suppressor, the retinoblastoma gene product (pRb-105). In view of these properties, we have undertaken the immunological analysis of this protein and have identified four T-cell epitopes and three B-cell epitopes by using a series of overlapping peptides spanning the entire HPV16 E7 sequence. Two of the B-cell epitopes were recognized by antisera from mice with three different murine (H-2) haplotypes (k, d, and s) immunized with two different E7 fusion proteins and from Fischer rats seeded with baby rat kidney cells transformed by HPV16 E7 and ras. A third B-cell epitope was recognized by antisera from CBA mice seeded with HPV16 E7-expressing L cells. Two regions of the protein contain common B- and T-cell epitopes, one of which appears to be particularly immunodominant.
有确凿证据表明16型人乳头瘤病毒（HPV16）与人类生殖器癌的发生有关。在子宫颈浸润癌以及源自宫颈癌的细胞系中已鉴定出病毒DNA。这些序列被积极转录，并且已鉴定出与早期（E）区域基因相对应的翻译产物。最丰富的病毒蛋白是E7蛋白，已证明它对已建立的细胞和原代细胞均具有转化活性。此外，它已被证明能与一种细胞肿瘤抑制因子，即视网膜母细胞瘤基因产物（pRb - 105）结合。鉴于这些特性，我们对该蛋白进行了免疫学分析，并通过使用一系列跨越整个HPV16 E7序列的重叠肽鉴定出了四个T细胞表位和三个B细胞表位。其中两个B细胞表位被用两种不同的E7融合蛋白免疫的具有三种不同鼠（H - 2）单倍型（k、d和s）的小鼠以及接种了由HPV16 E7和ras转化的幼鼠肾细胞的费希尔大鼠的抗血清所识别。第三个B细胞表位被接种了表达HPV16 E7的L细胞的CBA小鼠的抗血清所识别。该蛋白的两个区域包含共同的B细胞和T细胞表位，其中一个似乎具有特别的免疫显性。
