1997 Fiscal Year Final Research Report Summary
Molecular analysis for TCR-MHC-peptide interaction in thymic selection in vitro and in vivo
| Project/Area Number |
08839017
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
免疫の制御機構
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| Research Institution | Kyushu University |
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Principal Investigator |
FUKUI Yoshinori Medical Institute of Bioregulation, Kyushu University, Research Associate, 生体防御医学研究所, 助手 (60243961)
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| Co-Investigator(Kenkyū-buntansha) |
KAMIKAWAJI Nobuhiro Medical Institute of Bioregulation, Kyushu University, Associate Professor, 生体防御医学研究所, 助教授 (90224659)
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| Project Period (FY) |
1996 – 1997
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| Keywords | a single MHC / peptide complex / T cell receptor / GPI / transgenic mice / thymic selection |
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| Research Abstract |
The T cell repertoire is shaped by positive and negative selection through the interaction of alphabeta T cell receptor with self-peptide bound to self-major histocompatibility complex (MHC). To elucidate TCR/MHC/peptide interaction determining this reciprocal selection process, we have tried to develop in vitro and in vivo system where a single MHC/peptide ligand is expressed.
First, we developed a soluble MHC molecule of which cytoplasimic domain has been replaced with glycosyl-phophatidylinositol (GPI). This molecule complexed with a single peptide was found to be expressed on the cell-surface of any cells, by just incubation the complex with cells. However, the GPI anchored MHC/peptide complex expressed on thymic epithelial cells could not support T cell differentiation.
Second, we developed transgenic mouse lines expressing MHC molecules covalently bound to a single peptide at different levels in the thymus. By comparing the fate of T cells in these lines, we found that a single MHC/peptide ligand, depending on the expression level in thymus, can serve as both positively and negatively selecting ligand.
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