| Project/Area Number |
08044302
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| Research Category |
Grant-in-Aid for international Scientific Research
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| Allocation Type | Single-year Grants |
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| Section | Joint Research |
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| Research Field |
Immunology
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| Research Institution | Kyushu University |
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Principal Investigator |
SASAZUKI Takehiko Medical Institute of Bioregulation, Kyushu University, Professor, 生体防御医学研究所, 教授 (50014121)
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| Co-Investigator(Kenkyū-buntansha) |
FUKUI Yoshinori Medical Institute of Bioregulation, Kyushu University, Associate Professor, 生体防御医学研究所, 助教授 (60243961)
MOMBURG Frank German Cancer Research Center, Assistant Professor, 助手
VOGT Anne B. German Cancer Research Center, Assistant Professor, 助手
KROPSHOTER H ドイツ癌研究所, 助手
HAMMERLING Gunter German Cancer Research Center, Professor, 教授
KROPSHOFER Harald German Cancer Research Center, Assistant Professor
KROPSHOFER H ドイツ癌研究所, 助手
上川路 信博 九州大学, 生体防御医学研究所, 助教授 (90224659)
HAMMERLING G ドイツ癌研究所, 教授
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| Project Period (FY) |
1996 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥9,000,000 (Direct Cost: ¥9,000,000)
Fiscal Year 1998: ¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 1997: ¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 1996: ¥3,000,000 (Direct Cost: ¥3,000,000)
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| Keywords | TCR / MHC / peptide / HLA-DM / T cell repertoire selection / kinetic stability / 免疫寛容 / 単-MHC / ペプチド複合体 / トランスジェニックマウス / ノックアウトマウス / 主要組織適合抗原 / T細胞受容体 / 抗原ペプチド / プロセシング / HLA-DO / 免疫制御 / 胸腺内T細胞の選択 / TAP / 胸腺T細胞の選択 |
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| Research Abstract |
Immunological tolerance is established by elimination or inactivation of self-reactive T cells through TCR-MHC-peptide interaction in the thymus or periphery. To better understand the molecular mechanism for immunological tolerance, we focused on the generation of MHC/peptide complex and its recognition by TCRs, and obtained several new findings.
We revealed that HLA-DM functions as an editor of MHC class II-binding peptides. This would raise the new possibility that the kinetic stability of MHC class II/peptide complex play a important role in tolerance induction. The development and analysis of transgenic-knockout mouse lines expressing a single MHC class IIIpeptide complex brought several new insights into T cells repertoire selection. In addition, we found that organ-specific autoimmunity spontaneously develops in one of such mouse lines, which would argue against the currently prevailing paradigm for MHC class II association with autoimmune diseases.
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