Tumor-specific immunity can be enhanced by transfection of tumor cells with syngeneic MHC-class-II genes or allogeneic MHC-class-I genes
✍ Scribed by S. Ostrand-Rosenberg; C. Roby; V. K. Clements; G. A. Cole
- Publisher
- John Wiley and Sons
- Year
- 1991
- Tongue
- French
- Weight
- 675 KB
- Volume
- 47
- Category
- Article
- ISSN
- 0020-7136
No coin nor oath required. For personal study only.
✦ Synopsis
Mouse Sal sarcoma cells are lethal in the autologous A/J (K") host. In order t o improve the immune response t o the Sal tumor, Sal cells have been transfected with syngeneic MHC-class-ll or allogeneic MHC-class4 genes. MHC-class-ll transfectants are uniformly rejected by the autologous host and immunization with them protects against subsequent Sal challenge. The improved immunity is probably the result of enhanced generation of tumor-specific T, cells. We hypothesize that class-Il+ tumor cells trigger an improved T,-cell response because they directly present Sal tumor antigens in the context of class-ll molecules to T, cells, by-passing professional APC. Studies by others have demonstrated that antigen presentation requires an intracellular signal transmitted by the cytoplasmic domain of the APC class-ll molecule. Sal cells expressing class-It antigens with truncated cytoplasmic domains are as malignant as wild-type Sal cells. These experiments therefore support the role of tumor-cell class-ll molecules as antigen presentation elements, and demonstrate the requirement for intact class-ll molecules for tumor protection. Sal cells have also been transfected with allogeneic MHC-class-l genes. Although Kb-transfected cells are not rejected by A/J mice, Db-transfected Sal cells and Kb-plus Db-transfected cells are rejected. The Db transfectants effectively immunize A/J mice against subsequent Sal challenge. These experiments demonstrate that expression of certain allogeneic MHC-class4 genes can lead to tumor-specific immunity, and that such transfectants can protect against challenges of wild-type tumor cells. Transfection of tumor cells with syngeneic MHC-class4 or allogeneic MHC-class4 genes may therefore be a potential strategy for improving tumor-specific immunity in the autologous host.