Jochmus I, Osen W, Altmann A, Buck G, Hofmann B, Schneider A, Gissmann L, Rammensee H G
Deutsches Krebsforschungszentrum, Heidelberg, Germany.
J Gen Virol. 1997 Jul;78 ( Pt 7):1689-95. doi: 10.1099/0022-1317-78-7-1689.
In order to establish tumour-specific cytotoxic T lymphocyte (CTL) cell lines, T cells from a human papillomavirus (HPV) type 16-positive patient with a cervical carcinoma in situ and from a healthy volunteer were stimulated in vitro with autologous dendritic cells loaded with peptides derived from the viral transforming proteins E6 and E7 and corresponding to potential HLA-A0201-restricted T cell epitopes. From each donor a small number of low-affinity CTL lines against the peptide E7/86-93 was obtained, which specifically lysed HLA-A0201-expressing B-lymphocytes (cell line 721) loaded with this peptide. Cytotoxicity was also observed against two HLA-A*0201-E7-positive epithelial cell lines, the cervical carcinoma cell line CaSki and the HPV-16-immortalized foreskin-keratinocyte cell line HPK IA. However, since none of the CTL recognized both cell lines, and E7-expressing 721 transfectants were never lysed, it was concluded that the reactivity against CaSki and HPK IA cells was due to cross-reactivity on allogeneic HLA molecules rather than to E7 recognition, which emphasizes that the specificity of tumour cell lysis by peptide-induced CTL has to be interpreted with caution.
为建立肿瘤特异性细胞毒性T淋巴细胞（CTL）细胞系，从一名人乳头瘤病毒（HPV）16型原位宫颈癌患者及一名健康志愿者体内获取T细胞，在体外使用负载有源自病毒转化蛋白E6和E7且对应潜在HLA - A0201限制性T细胞表位的肽段的自体树突状细胞进行刺激。从每个供体获得了少量针对肽段E7/86 - 93的低亲和力CTL系，这些CTL系可特异性裂解负载该肽段的表达HLA - A0201的B淋巴细胞（721细胞系）。还观察到对两种HLA - A*0201 - E7阳性上皮细胞系的细胞毒性，即宫颈癌细胞系CaSki和HPV - 16永生化包皮角质形成细胞系HPK IA。然而，由于没有一个CTL能识别这两种细胞系，且表达E7的721转染细胞从未被裂解，因此得出结论，对CaSki和HPK IA细胞的反应性是由于对同种异体HLA分子的交叉反应而非对E7的识别，这强调了肽诱导的CTL对肿瘤细胞的裂解特异性必须谨慎解读。
