| Project/Area Number |
60440037
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| Research Category |
Grant-in-Aid for General Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Research Field |
Immunology
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| Research Institution | University of Tokyo |
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Principal Investigator |
TADA Tomio University of Tokyo, Professor, 医学部, 教授 (10009136)
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| Co-Investigator(Kenkyū-buntansha) |
YANAGI Yusuke University of Tokyo, Assistant Professor, 医学部, 助手 (40182365)
ASANO Yoshihiro University of Tokyo, Associate Professor, 医学部, 助教授 (70114353)
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| Project Period (FY) |
1985 – 1988
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| Project Status |
Completed (Fiscal Year 1988)
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| Budget Amount *help |
¥29,000,000 (Direct Cost: ¥29,000,000)
Fiscal Year 1988: ¥4,800,000 (Direct Cost: ¥4,800,000)
Fiscal Year 1987: ¥3,900,000 (Direct Cost: ¥3,900,000)
Fiscal Year 1986: ¥8,300,000 (Direct Cost: ¥8,300,000)
Fiscal Year 1985: ¥12,000,000 (Direct Cost: ¥12,000,000)
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| Keywords | T cell receptor / chain / I-J / Major histocompatibility complex / Restriction specificity / 組織適合遺伝子複合体 / 抑制T細胞 / 遺伝子再構成 / 遺伝的拘束 / 突然変異 / 遺伝子表現の排徐 / T細胞クローン / モノクローナル抗体 / 主要組織適合遺伝子複合体 / T細胞レセプター遺伝子 |
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| Research Abstract |
T cells recognize antigen in context of major histocompatibility complex (MHC) class I or calss II antigens. In addition, it has been known that suppressor T cells (Ts) suppress the responses of other T cells with a genetic restriction imposed by the I-J antigen, whose genes have not been identified. Both above genetic restrictions are known to be adaptively acquired by T cells during their early ontogeny in the thymus under the influence of environmental MHC.
In order to elucidate the origin of MHC restrictions, we produced a large number of T cell clones from normal, F_1 and mice of radiation bone marrow chimeras. The cells were selected by the stimulation with antigen-presenting cells of different MHC haplotypes. The MHC restriction specificities of these clones with respect to antigen- and target cell interactions have been studied in parallel with the analysis of TcR and genes, and of expression of I-J molecules. It has been demonstrated that restriction-specificities of TcR and I-J on the same T cell clone are not necessarily identical, indicating that they are controlled by different genes. One of the T cell clones showed one and two genes rearranged in-frame, while only one gene was expressed on the cell surface. This clone had sequential changes in the restriction specificity suggesting that T cells may change restriction specificity after maturation. Finally we identified biochemically the I-J molecule in two dimensional gel as a molecular weight 86K dimer composed of two 43K glycopeptide subunits. The expression of this molecule in bone marrow chimeras was found to be adaptive to the thymic MHC.
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