| Project/Area Number |
11694289
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Immunology
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| Research Institution | KYUSHU UNIVERSITY |
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Principal Investigator |
FUKUI Yoshinori Medical Institute of Bioregulation, Kyushu University, Associate Professor, 生体防御医学研究所, 助教授 (60243961)
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| Co-Investigator(Kenkyū-buntansha) |
HASHIMOTO Osamu Medical Institute of Bioregulation, Kyushu University, Assistant Professor, 生体防御医学研究所, 助手 (50289427)
YAMAMOTO Ken Medical Institute of Bioregulation, Kyushu University, Associate Professor, 生体防御医学研究所, 助教授 (60274528)
SASAZUKI Takehiko International Medical Center of Japan, Research Institute, Director, 研究所, 所長 (50014121)
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| Project Period (FY) |
1999 – 2001
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| Keywords | MHC / T cell receptor / antigenic peptides / positive and negative selection / autoimmunity |
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| Research Abstract |
T cell repertoire is shaped through the recognition of MHC/self-peptide complex by TCRs in the thymus. However, diversity of self-peptide precluded analyzing this interaction at a molecular level. To overcome this problem, we have developed transgenic-knockout mice where MHC molecules are occupied with a single defined peptide. By analyzing these mice, we found that 1) the same MHC/peptide complex, being affected by its expression level in the thymus, can serve as a ligand for both positive and negative selection and 2) while specific TCR-peptide interaction is involved even in positive selection, the amino acid residue of the peptides at TCR-contact remarkably affects the diversity of the selected T cell repertoire. On the other hand, it is well known that particular MHC alleles are associated with the susceptibility to organ-specific autoimmune diseases. We found that a line of transgenic-knockout mice expressing a single MHC/peptide complex at a quite low level in the thymus spontaneously develops peripheral nervous-specific autoimmune diseases. Since MHC molecules are accupied with a single defined peptide in these mice, these results suggest that MHC molecules determine the susceptibility to autoimmune diseases through T cell repertoire selection in the thymus.
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