比较负载高危型HPV-16E6和低危型HPV-11E6的树突状细胞抗原递呈功能的研究

项目名称： 比较负载高危型HPV-16E6和低危型HPV-11E6的树突状细胞抗原递呈功能的研究

项目编号： No.81201273

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学四处

项目作者： 孙丽娜

作者单位： 中国疾病预防控制中心传染病预防控制所

项目金额： 23万元

中文摘要： 负载肿瘤抗原的树突状细胞(DC)诱导抗原特异性的细胞免疫,进行肿瘤杀伤, 成为宫颈癌免疫治疗新的方向。HPV-16E6癌基因转染DC后，虽诱导产生细胞毒T细胞(CTL)的方法已成熟，但其肿瘤杀伤能力尚不清楚。更值得关注的是低危型HPV-11E6转染DC后，是否也会产生CTL进行肿瘤杀伤，未见报道。我们前期工作证实，高危型HPV-16E6和低危型HPV-11E6在细胞的定位及作用不同。因此，本课题拟通过向DC内分别转染高危型HPV-16E6和低危型HPV-11E6，比较它们在DC的定位及对DC抗原递呈和效应CTL的肿瘤杀伤能力，进一步将高危型HPV-16E6核定位信号NLS插入低危型HPV-11E6，使之入核，如果入核的低危型HPV-11E6能增加对DC抗原递呈和效应CTL的肿瘤杀伤能力，以低危型HPV-11E6作为候选抗原来抗肿瘤，将大大增加疫苗的安全性，为治疗性HPV疫苗的研究提供思路。

中文关键词： 树突细胞；HPV；免疫；凋亡；CD103

英文摘要： It has become an emerging field of cervical cancer theraphy that dentritic cell loaded with neoplasm antigen can induce specific cellular immunity to kill cancer cells. It has reported the oncogene HPV-16E7 and HPV-16E6E7 both can pulse DC to induce CTL associated cancer killing. Although the oncogene HPV-16E6 can induce CTL, the exact capacity of CTL to kill cancer cells has not been determined yet. More importantly, it is not known whether the DC transfected with low risk HPV-11E6 can pulse CTL to kill cancer. In our previous study, we have verified the different location of high risk HPV-16E6 and low risk HPV-11E6 in 293T and MCF-7 cells. The high risk HPV-16E6 was mainly located in nulear,whearas the low risk HPV-11E6 was mainly located in cytoplasm in 293T and MCF-7 cells. It has reported that subcellular antigen location influenced CD8+CTL activation .The purpose of the present project is to check the location of high risk HPV-16E6 and low risk HPV-11E6 in DC and compare the CTL effect induced by them.Furthermore,we plan to insert nuclear location signal(NLS) of high risk HPV-16E6 to low risk HPV-11E6 sequence which named NLS-HPV-11E6.To further compare the antigen presenting function of DC and CTL effect induced by NLS-HPV-11E6 with those induced by HPV-11E6. Maybe the nuclear located NLS-HPV-11E6 can en

英文关键词： dendritic cells；HPV；immunology；apoptosis；CD103