| Project/Area Number |
08670369
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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 |
Immunology
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| Research Institution | KYUSHU UNIVERSITY |
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Principal Investigator |
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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| Co-Investigator(Kenkyū-buntansha) |
FKUI Yoshinori Medical Institute of Bioregulation, Kyushu University, Research Associate, 生体防御医学研究所, 助手 (60243961)
SHIRASAWA Senji Medical Institute of Bioregulation, Kyushu University, Research Associate, 生体防御医学研究所, 助手 (10253535)
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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| Project Period (FY) |
1996 – 1997
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| Project Status |
Completed (Fiscal Year 1997)
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| Budget Amount *help |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1997: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1996: ¥1,200,000 (Direct Cost: ¥1,200,000)
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| Keywords | HLA / transgenic mouse / HLA-DR / allogeneic response / xenogeneic response / 移植 / HLA-DQ6 / 自己抗原ペプチド / 異種MLR |
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| Research Abstract |
Although T cells are educated to recognize foreign antigenic peptides in the context of self MHC molecules during their development in the thymus, peripheral T cells also recognize allo- and xeno- MHC molecules. The lower frequency of xeno-MHC-reactive T cells than that of allo-MHC-reactive T cells is often explained by the difference in the degree of homology between xeno- or allo-MHC and self MHC molecules, as well as by the species barrier of the molecules involved in immune recognition. To distinguish these two possibilities, we estimated the frequency of I-Ab-reactive CD4^+ T cells selected by HLA-DQ or DRalphaEbeta^b molecules, using HLA-DQ6 and HLA-DRA transgenic C57BL/6 (B6) mice lacking endogenous MHC class I and/or class II molecules (DQ6A^<0/0> and DRalpha30A^<0/0>beta_2^<0/0>). CD4^+ lymph node T cells from DQ6A^<0/0> and DRalpha30A^<0/0>beta_2^<0/0 > showed the strong proliferative response to I-A^b molecules. In addition, DQ6A^<0/0> and DRalpha30A^<0/0>beta_2^<0/0> rejected the skin grft from mice expressing I-A^b molecules irrespective of MHC class I expression, indicating that the CD4^<+n> T cells recognizing I-A^<bn> molecules are directly involved in this rejection. The estimated frequency of I-A^b-reactive CD4^+CD8^- thymocytes in DRalpha30A^<0/0>beta_2^<0/0> and DQ6A0/0 was comparable with that observed in the MHC class II-disparate strains. Our findings thus indicate that CD4^+ T cells selected to mature on xeno-MHC class II molecules such as HLA-DQ6 or DRalphaEbeta^b, when these molecules are expressed in mice, recognize I-A^b molecules as allo-MHC class II,despite the less structural homology.
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