| Budget Amount *help |
¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 1993: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1992: ¥1,000,000 (Direct Cost: ¥1,000,000)
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| Research Abstract |
It is now widely accepted that self proteins are continuously processed and presented as peptides in association with self MHC molecules for interaction with T cells. Tumor-specific or tumor-associated antigens(TSTA, TAA) are also asuumed to be presented on a tumor cell or an antigen-presenting cell (APC), complexing with the avairable MHC molecules, although the molecular mechanisms are presently poorly understood. In the field of radiation biology, there has been a hypothesis that ionizing radiation induces the changes in immunogenicity of the tumor (i.e enhanced immunogenicity). In this study, Itried to detect possible immunogenic changes by radiation, analysing T cell antigen receptor (TCR) Vbeta chain repertoire of sensitized T cells to a murine hepatoma, MH134. The results obtained were the followings : (1) 20Gy irradiation to the tumor in vivo or immunization with 100Gy-irradiated tumor cells enhanced tumor rejection in syngeneic mice. It was shown that irradiated tumor cells readily induced CD4+ helper cells and in consequence of T - T cooperation, generation of cytotoxic T cell was promoted. (2) Isolated CD4+ and CD8+ clones from these mice exhibited both Th1 and Th2 pattern of lymphokine gene expression, when stimulated with sonicated MH134 and APC.(3) Flow-cytometric analysis using monoclonal antibodies agaist TCR Vbeta gene products as well as RT-PCR analysis revealed Vbeta6 usage of sensitized T cells to MH134. Irradiation of the tumor did not change this limitted usage of Vbeta gene during the seguential analysis of TCR up to 1 month after irradiation. (5) All of the T cell clones (8 clones) established from tumor-infiltrating lympho-cytes (TIL) has also Vbeta6. Since analysis of Valpha chain repertoire has not been completed, any conclusion, however, could be drawn from these findings. To get a conclusion, further analysis will be continued. TCR analysis of human tumors (especially carcinoma of tongue and mammary tumors) in relation to radiation-ther
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