Zhu X, Tommasino M, Vousden K, Sadovnikava E, Rappuoli R, Crawford L, Kast M, Melief C J, Beverley P C, Stauss H J
MCR Tuberculosis and Related Infections Unit, Royal Postgraduate Medical School, Hammersmith Hospital, London, UK.
Scand J Immunol. 1995 Nov;42(5):557-63. doi: 10.1111/j.1365-3083.1995.tb03696.x.
The transforming protein E7 of human papilloma virus type 16 can stimulate cytotoxic T lymphocytes (CTL) which can protect experimental animals against growth of E7 expressing tumour cells. In this study we compared CTL responses in mice immunized with either E7 protein in MF59 adjuvant or with recombinant vaccinia virus expressing E7 (Vac-E7). We have chosen H-2d mice because no E7-specific CTL responses have been described in this MHC haplotype. Immunization of these mice with Vac-E7 generated CTL which lysed target cells infected with Vac-E7 or transfected with the E7 gene. CTL from mice immunized with E7 protein in MF59 adjuvant showed specificity for the same target cells. Antibody blocking experiments revealed that both immunization with Vac-E7 and E7 protein stimulated CD8+ effector CTL. The find specificity of CTL induced by the two immunization protocols was similar. A major CTL epitope was mapped to the carboxyl terminal amino acids 48-98 of the E7 protein. Peptide isolation from E7 expressing cells followed by HPLC separation indicated that CTL induced by immunization with protein and Vac-E7 recognized the same HPLC purified peptide fractions. Together, the study suggests that vaccines based on protein can activate CTL with similar fine specificity to CTL induced by vaccines based on recombinant vaccinia virus.
人乳头瘤病毒16型的转化蛋白E7可刺激细胞毒性T淋巴细胞(CTL),后者能够保护实验动物抵抗表达E7的肿瘤细胞的生长。在本研究中,我们比较了用MF59佐剂中的E7蛋白或表达E7的重组痘苗病毒(Vac-E7)免疫的小鼠的CTL反应。我们选择了H-2d小鼠,因为在这种MHC单倍型中尚未描述E7特异性CTL反应。用Vac-E7免疫这些小鼠可产生CTL,其可裂解被Vac-E7感染或用E7基因转染的靶细胞。用MF59佐剂中的E7蛋白免疫的小鼠的CTL对相同的靶细胞具有特异性。抗体阻断实验表明,用Vac-E7和E7蛋白免疫均刺激了CD8 +效应CTL。两种免疫方案诱导的CTL的发现特异性相似。一个主要的CTL表位被定位到E7蛋白的羧基末端氨基酸48-98。从表达E7的细胞中分离肽,然后进行HPLC分离,表明用蛋白和Vac-E7免疫诱导的CTL识别相同的HPLC纯化肽级分。总之,该研究表明基于蛋白的疫苗可以激活CTL,其精细特异性与基于重组痘苗病毒的疫苗诱导的CTL相似。