Bauer M, Wagner H, Lipford G B
Institute of Medical Microbiology, Immunology and Hygiene, Munich, Germany.
Immunol Lett. 2000 Jan 10;71(1):55-9. doi: 10.1016/s0165-2478(99)00170-4.
Human papillomaviruses (HPV) have been implicated in the etiology of cervical malignancies and a high percentage of cervical carcinoma cells express HPV-16 E6 and E7 oncoproteins. These proteins are attractive targets for cytolytic T lymphocyte (CTL) mediated immunotherapy. We screened peptides derived from the HPV-16 E7 protein for binding to HLA-A2 and tested their potential to induce specific CTL responses in chimeric HLA-A2/H2-Kb transgenic mice. From eight potential binding peptides four displayed binding and were tested for immunogenicity. CTL activity was tested using target cells pulsed with peptide or expressing E7 protein. While there was no CTL induction observed with the peptides 7-15, 66-74 and 82-90, CTL from mice immunized with 86-93 lysed targets presenting the peptide in the context of the HLA-A2/H2-Kb molecule or wild-type HLA-A2. In contrast, 86-93 induced CTL showed no cytolytic activity against cells expressing the protein E7 and vaccination with the E7 protein did not lead to cytotoxicity against targets pulsed with the 86-93 peptide. Therefore the peptide 86-93, which binds to HLA-A2, is able to induce CTL responses in context of HLA-A2, but the peptide appears not to be processed or presented by HPV type 16 infected cells.
人乳头瘤病毒（HPV）与宫颈癌的病因有关，并且高比例的宫颈癌细胞表达HPV-16 E6和E7癌蛋白。这些蛋白是细胞溶解性T淋巴细胞（CTL）介导的免疫疗法的有吸引力的靶点。我们筛选了源自HPV-16 E7蛋白的肽与HLA-A2的结合情况，并测试了它们在嵌合HLA-A2/H2-Kb转基因小鼠中诱导特异性CTL反应的潜力。从八个潜在的结合肽中，四个显示出结合能力，并对其免疫原性进行了测试。使用用肽脉冲或表达E7蛋白的靶细胞测试CTL活性。虽然用肽7-15、66-74和82-90未观察到CTL诱导，但用86-93免疫的小鼠的CTL裂解了在HLA-A2/H2-Kb分子或野生型HLA-A2背景下呈递该肽的靶细胞。相反，86-93诱导的CTL对表达蛋白E7的细胞没有细胞溶解活性，并且用E7蛋白进行疫苗接种不会导致对用86-93肽脉冲的靶细胞产生细胞毒性。因此，与HLA-A2结合的肽86-93能够在HLA-A2背景下诱导CTL反应，但该肽似乎不会被16型HPV感染的细胞加工或呈递。
