CTL公司*
启动(农业)
细胞毒性T细胞
小基因
生物
表位
抗原
MHC I级
T细胞
主要组织相容性复合体
细胞生物学
免疫系统
免疫学
体外
CD8型
遗传学
信使核糖核酸
基因
发芽
植物
选择性拼接
作者
Stephen P. Schoenberger,Liesbeth E. Jonges,R. J. D. Mooijaart,Franca C. Hartgers,René Toes,W. Martin Kast,Cornelis J.M. Melief,Rienk Offringa
出处
期刊:PubMed
日期:1998-07-15
卷期号:58 (14): 3094-100
被引量:22
摘要
Although numerous studies have documented a role for B7-1 (CD80) in the induction of antitumor CTL immunity, it is presently unclear to what extent expression of this costimulatory molecule truly endows tumors with significant in vivo APC (antigen-presenting cell) capacity. Recent studies have, in fact, demonstrated that cross-priming, rather than direct priming, may constitute the major mechanism of CTL induction by B7-1 expressing tumors. We have, therefore, investigated the requirements for antigen density and costimulatory molecules in direct CTL priming with a prototype cell-based vaccine that uses a signal sequence-containing minigene to direct expression of a tumor-specific CTL epitope to the endoplasmic reticulum. This design limits sources of antigen available to professional APC in the host and, thereby, the contribution of cross-priming. Induction of antitumor CTL immunity by our prototype APC was shown to solely involve direct priming, independent of host APC, NKI.1+ cells, and CD4+ T cell help. CTL induction through this mechanism required the engineered APC to express the B7-1 molecule as well as a sufficiently high density of peptide/MHC complexes at its surface. Our data, in contrast to previous studies using modified tumor cells, clearly define the antigenic and costimulatory requirements for a suitably engineered "artificial" APC to directly prime peptide-specific CTL in vivo, and demonstrate that the signal sequence minigene approach allows the engineering of highly effective and well-defined cellular vaccines for activation of CTL against epitopes of choice.
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