Skipper J, Stauss H J
Imperial Cancer Research Fund, Courtauld Institute of Biochemistry, London, United Kingdom.
J Exp Med. 1993 May 1;177(5):1493-8. doi: 10.1084/jem.177.5.1493.
We have investigated the possibility of inducing cytotoxic T lymphocytes (CTL) to Ras containing a mutation at position 61 or to normal Ras, using recombinant vaccinia viruses expressing these proteins. CTL from C57Bl/10 mice immunized with vaccinia expressing mutant Ras showed specificity for the mutant Ras protein and recognition of normal Ras was inefficient. The opposite specificity was observed after immunization with vaccinia expressing normal Ras, since CTL isolated from these mice recognized normal Ras well and mutant Ras inefficiently. Levels of endogenous Ras expression were insufficient for lysis by these CTL. One CTL epitope mapped to amino acids 60-67 and residue 61 was critical for T cell recognition. CTL generated against mutant Ras protein recognized peptide 60-67 containing mutant residue 61, while anti-normal Ras CTL recognized the wild-type 60-67 sequence. A second epitope mapped to residues 152-159 of Ras and was recognized equally well by CTL raised to normal or mutant Ras. The murine data raise the possibility of exploiting Ras-specific CTL for targeted immunotherapy of certain human cancers.
我们利用表达这些蛋白质的重组痘苗病毒，研究了诱导细胞毒性T淋巴细胞（CTL）针对第61位含有突变的Ras或正常Ras的可能性。用表达突变型Ras的痘苗免疫的C57Bl/10小鼠的CTL对突变型Ras蛋白具有特异性，而对正常Ras的识别效率较低。在用表达正常Ras的痘苗免疫后观察到相反的特异性，因为从这些小鼠中分离的CTL能很好地识别正常Ras，而对突变型Ras的识别效率较低。内源性Ras的表达水平不足以被这些CTL裂解。一个CTL表位定位于氨基酸60 - 67，第61位残基对T细胞识别至关重要。针对突变型Ras蛋白产生的CTL识别含有突变型残基61的肽60 - 67，而抗正常Ras的CTL识别野生型60 - 67序列。第二个表位定位于Ras的152 - 159位残基，被针对正常或突变型Ras产生的CTL同等程度地识别。小鼠实验数据增加了利用Ras特异性CTL对某些人类癌症进行靶向免疫治疗的可能性。
