IMMUNE RESPONSES TO HPVS INVOLVED IN GENITAL NEOPLASIA

人乳头瘤病毒（HPV）与良性和恶性肿瘤有关。 鳞状上皮增生性病变。 宿主对 HPV感染没有很好地表征，部分原因是HPV编码的 用作抗原靶的蛋白质难以获得。 HPV感染 仅人类鳞状上皮细胞，并且通常不复制 到自然感染组织中的高密度。 HPV还没有被 在组织培养细胞中成功繁殖，人类是唯一的 已知的动物宿主。 作为HPV编码蛋白的替代来源， 作为免疫反应性测定中的抗原，我们表达了DNA 来自克隆的HPV 6b、HPV 16和HPV 16的开放阅读框（ORF）的片段， HPV18 DNA在大肠杆菌中的重组遗传技术。 这些 HPV类型特别令人感兴趣，因为它们与 女性生殖道的生物学上不同的疾病：HPV 6b是最常见的 常见于常见的生殖器疣（尖锐湿疣），HPV 16和 HPV 18常与子宫颈发育不良相关， 宫颈癌 HPV编码的蛋白质将用于免疫学研究。 本发明的目的在于解决以下几个问题：1）鉴定那些 良性和恶性HPV诱导体液和细胞免疫应答 女性生殖道疾病，2）以确定是否 对HPV 6b、HPV 16和HPV 18蛋白的反应性是类型特异性的， 交叉反应，3）表征免疫的自然史 HPV相关疾病的免疫反应，以及40个确定免疫 反应性通过治疗干预来改变。 的位置 体液和细胞免疫表位将通过使用核酸外切酶作图 III缺失的融合蛋白构建体和HPV衍生的合成肽。 该信息在进一步表征关系中可能是有价值的 HPV与生殖道良性和恶性疾病的关系， 评估治疗干预的效果，以及在发展HPV 疫苗。

Human papillomaviruses (HPVs) are associated with benign and malignant proliferative lesions of squamous epithelium. The host immune response to HPV infections is not well characterized, in part because HPV-encoded proteins to serve as antigen targets are difficult to obtain. HPVs infect exclusively human squamous epithelial cells, and generally do not replicate to high densities in naturally infected tissues. HPVs have not been successfully propagated in tissue culture cells, and humans are the only known animal host. As an alternative source of HPV-encoded proteins to serve as antigen in assays of immune reactivity, we have expressed DNA fragments from the open reading frames (ORFs) of cloned HPV6b, HPV16, and HPV18 DNAs in Escherichia coli be recombinant genetic techniques. These HPV types are of particular interest because they are associated with biologically distinct diseases of the female genital tract: HPV6b is most often found in common genital warts (condylomata acuminata), and HPV16 and HPV18 are frequently associated with uterine cervical dysplasia and cervical carcinoma. The HPV-encoded proteins will be used in immunological assays to address several issues: 1) to identify those HPV proteins which induce humoral and cellular immune responses in benign and malignant HPV diseases of the female genital tract, 2) to determine whether the reactivities to HPV6b, HPV 16, and HPV18 proteins are type-specific or cross-reactive, 3) to characterize the natural history of the immune responses in HPV-related diseases, and 40 to determine whether immune reactivities are modified by therapeutic intervention. The locations of humoral and cellular immune epitopes will be mapped by using exonuclease III-deleted fusion protein constructs and HPV-derived synthetic peptides. This information may be valuable in further characterizing the relationship of HPVs to benign and malignant diseases of the genital tract, in evaluating the effects of therapeutic interventions, and in developing HPV vaccines.