Altmann A, Jochmus-Kudielka I, Frank R, Gausepohl H, Moebius U, Gissmann L, Meuer S C
Department of Applied Immunology, German Cancer Research Centre, Heidelberg.
Eur J Cancer. 1992;28(2-3):326-33. doi: 10.1016/s0959-8049(05)80047-4.
Specific T lymphocyte lines and T cell clones were established from peripheral blood mononuclear cells of asymptomatic seropositive individuals employing synthetic peptides which correspond to the sequence of the human papillomavirus (HPV) type 16 transforming protein E7. Specificity analysis of T cells as determined by means of [3H] thymidine incorporation after stimulation with individual peptides revealed three immunogenic determinants of E7 that are recognised in association with at least two different HLA haplotypes. One N-terminal region (aminoacids 5-18) was recognised by one T cell line. T cell clones and the corresponding T cell line established from another donor responded to a different N-terminal (17-38) and to a C-terminal region (69-86). The N-terminal sequence 5-18 and the C-terminal determinant contain a periodicity of hydrophilic and hydrophobic residues that have been found in many T cell epitopes. Phenotypic characterisation of T cell clones by indirect immunofluorescence revealed that the T cell clones expressed the CD4 surface glycoprotein suggesting that the specific E7 determinants were recognised in association with major histocompatibility complex (MHC) class II molecules. With regard to functional properties, at least three T cell clones exhibited specific cytotoxic activity towards autologous B lymphocytes transformed by Epstein-Barr virus in the presence of the relevant HPV16 E7 peptides. The implications of these results regarding the development of vaccination strategies and host-virus interaction are discussed.
利用与人乳头瘤病毒（HPV）16型转化蛋白E7序列相对应的合成肽，从无症状血清阳性个体的外周血单核细胞中建立了特异性T淋巴细胞系和T细胞克隆。通过用单个肽刺激后[3H]胸苷掺入法测定的T细胞特异性分析显示，E7有三个免疫原性决定簇，它们与至少两种不同的HLA单倍型相关被识别。一个N端区域（氨基酸5 - 18）被一个T细胞系识别。从另一个供体建立的T细胞克隆和相应的T细胞系对不同的N端（17 - 38）和一个C端区域（69 - 86）有反应。N端序列5 - 18和C端决定簇含有亲水性和疏水性残基的周期性，这在许多T细胞表位中都有发现。通过间接免疫荧光对T细胞克隆进行表型特征分析显示，T细胞克隆表达CD4表面糖蛋白，提示特异性E7决定簇与主要组织相容性复合体（MHC）II类分子相关被识别。关于功能特性，至少三个T细胞克隆在相关HPV16 E7肽存在的情况下，对经爱泼斯坦 - 巴尔病毒转化的自体B淋巴细胞表现出特异性细胞毒性活性。讨论了这些结果对疫苗接种策略发展和宿主 - 病毒相互作用的意义。
