VACCINATION WITH CYTOTOXIC T-LYMPHOCYTE EPITOPE-CONTAINING PEPTIDE PROTECTS AGAINST A TUMOR-INDUCED BY HUMAN PAPILLOMAVIRUS TYPE-16-TRANSFORMED CELLS
VACCINATION WITH CYTOTOXIC T-LYMPHOCYTE EPITOPE-CONTAINING PEPTIDE PROTECTS AGAINST A TUMOR-INDUCED BY HUMAN PAPILLOMAVIRUS TYPE-16-TRANSFORMED CELLS
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DOI：
10.1002/eji.1830230929
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发表时间：
1993-09-01
影响因子：
5.4
通讯作者：
KAST, WM
中科院分区：
文献类型：
--
作者：
FELTKAMP, MCW;SMITS, HL;KAST, WM
细胞毒性T淋巴细胞（CTL）肽表位可用于小鼠免疫致死性病毒感染。为了研究这种方法是否能够成功地对抗病毒诱导的肿瘤，我们建立了一个由人乳头瘤病毒（HPV）转化的B6 （H-2b）致瘤细胞系。在90%以上的人类宫颈癌中检测到这种病毒。为了确定候选疫苗，我们从HPV16型（HPV16）癌基因E6和E7中提取了240个重叠肽。测试了这些肽结合H-2K(b)和H-2D(b) MHC I类分子的能力。结合肽与目前已知的H-2K(b)和H-2D(b)的肽结合基序进行了比较，并简要讨论了这些基序的预测价值。高亲和力的H-2D(b)结合肽和推测的CTL表位E7 49-57 （RAHYNIVTF）用于HPV 16转化肿瘤细胞的疫苗接种研究。用肽E7 49-57免疫小鼠，使小鼠在体内对HPV 16转化的肿瘤细胞不敏感，并诱导CTL反应，在体外裂解肿瘤细胞。
Cytotoxic T lymphocyte (CTL) peptide epitopes can be used for immunization of mice against lethal virus infection. To study whether this approach can be successful against virus-induced tumors we generated a B6 (H-2b) tumorigenic cell line transformed by human papillomavirus (HPV). This virus is detected in over 90% of all human cervical cancers. To identify vaccine candidates, we generated a set of 240 overlapping peptides derived from the HPV type 16 (HPV16) oncogenes E6 and E7. These peptides were tested for their ability to bind H-2K(b) and H-2D(b) MHC class I molecules. Binding peptides were compared with the presently known peptide-binding motifs for H-2K(b) and H-2D(b) and the predictive value of these motifs is shortly discussed. The high-affinity H-2D(b)-binding peptide and putative CTL epitope E7 49-57 (RAHYNIVTF) was used in vaccination studies against HPV 16-transformed tumor cells. Immunization with peptide E7 49-57 rendered mice insensitive to a subsequent challenge with HPV 16-transformed tumor cells in vivo, and induced a CTL response which lysed the tumor cells in vitro.