Induction and the epitope analysis of human T cells specitic for human papilloma virus

了解肿瘤细胞特异性的细胞免疫功能，对于研究恶性肿瘤的免疫监控系统具有重要意义。人乳头瘤病毒（HPV）是研究细胞免疫应答及其在慢性感染过程中诱发的肿瘤的有效工具，由于乳头状瘤病毒几乎被确定为约70%的人宫颈癌患者的病因，我们检测了溶细胞性T细胞（CTL）通过宫颈细胞的RT-PCR分析检测对来自感染受试者的外周血细胞的HPV 16 E6和E7癌基因的截短肽的应答。在150例HPV 16感染者中，有5例检测到CTL反应。并对这些CTL的最小T细胞表位进行了检测，确定了这些CTL的HLA限制性抗原和细胞表面标志。我们还以IL-2反应为标志诱导了HPV 16 E6和E7肽段特异性辅助性T细胞，并检测到几种HPV 16 E6和E7肽段特异性辅助性T细胞。我们试图在这些细胞中诱导特异性的辅助细胞和杀伤细胞克隆，以了解T细胞识别癌基因产物的机制。本研究拟通过研究这些细胞的最小抗原表位和HLA限制性，探讨宫颈癌的发病机制和宫颈癌肽疫苗的可能性。

In order to investigate immune surveilence system for malignant tumors, it is important to know cellular immunity specific for tumor cells. Human papillomaviruses (HPVs) an useful tool to study cellular immune response agaist viruses and cancers induced by the viruses during the chronic infection, bscause papillomaviruses is almost established to be the cause of human cervical cancers among about 70% of the patients.We tested the cytolytic T cell (CTL) response against the truncated peptides of HPV16 E6 and E7 oncogenes from peripheral blood cells of the infected subjects detected by RT-PCR analysis of cervical cells. We could detect the CTL rsponse in 5 subjects among 150 subjects in HPV16- infected subjects. We also try to detect the minimum T cell epitopes of these CTL, and determine the HLA restriction and cell surface marker of these cells. We also induced the helper T cells specific for HPV16 E6 and E7 peptides using IL-2 response as the marker, and also detected several helper T cells specific for these petides. We try to induce the specific helper and killer clones in these cells, to know the mechanisms of T cell recognition agaist the oncogene products. We would like to study the minimum epitopes of these cells and HLA restriction to investigate the pathogenesis of cervical cancer, and the possibility of peptide vaccine for cervical neoplasms.