Tobery T, Siliciano R F
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
J Immunol. 1999 Jan 15;162(2):639-42.
There is much interest in vaccines that will enhance the induction of CTL. One mechanism to enhance Ag-specific CTL responses involves targeting Ag to undergo rapid cytoplasmic degradation by the N-end rule pathway. We have analyzed the ability of N-end rule targeting to confer protection in an immunization-challenge setting. Using the HIV-1 nef protein as a model tumor Ag, we found that in mice immunized with a vaccinia vector expressing a form of nef that is targeted for rapid cytoplasmic degradation, there was enhanced induction of nef-specific CTL and protection from a lethal challenge with the syngeneic CT26 tumor cells that had been transfected with nef. Protection from tumor challenge correlated with the magnitude of the CTL response. Thus, the targeting of tumor or viral Ags for rapid cytoplasmic degradation by the N-end rule pathway may represent a strategy for the induction of protective Ag-specific CTL responses in vivo.
人们对能够增强细胞毒性T淋巴细胞（CTL）诱导的疫苗有着浓厚兴趣。增强抗原特异性CTL反应的一种机制是将抗原靶向通过N端规则途径进行快速胞质降解。我们分析了N端规则靶向在免疫-攻击环境中赋予保护的能力。以HIV-1 nef蛋白作为模型肿瘤抗原，我们发现，在用表达一种靶向快速胞质降解形式的nef的痘苗载体免疫的小鼠中，nef特异性CTL的诱导增强，并且能抵御用转染了nef的同基因CT26肿瘤细胞进行的致死性攻击。抵御肿瘤攻击与CTL反应的强度相关。因此，通过N端规则途径将肿瘤或病毒抗原靶向进行快速胞质降解可能代表了一种在体内诱导保护性抗原特异性CTL反应的策略。
