| Project/Area Number |
62570210
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Immunology
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| Research Institution | Hokkaido University |
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Principal Investigator |
WAKISAKA Akemi Hokkaido University School of Medicine., 医学部, 助手 (90113646)
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| Co-Investigator(Kenkyū-buntansha) |
NATORI Takashi Hokkaido University School of Medicine., 医学部, 助手 (00001892)
KIKUCHI Yuhko Hokkaido University School of Medicine., 医学部, 講師 (60002119)
相沢 幹 北海道大学, 医学部, 教授 (70000891)
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| Project Period (FY) |
1987 – 1988
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| Project Status |
Completed (Fiscal Year 1988)
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| Budget Amount *help |
¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1988: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1987: ¥1,200,000 (Direct Cost: ¥1,200,000)
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| Keywords | HLA-DQ antigen / Insulin-dependent Diabetes mellitus / 宿主要因 / 拘束分子 / HLA / RFLP解析 |
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| Research Abstract |
A novel HLA-DQ antigen, which is in strongly linkage disequilibrium with A24-BW54-CW1-DR4-DW15 haplotype in Japanese, was defined by monoclonal antibody HU-46 and cytotoxic T-cell clones. This antigen, tentatively called as DQWa, has been officially designated as DQw4 by WHO nomenclature committee after numerous discussions at 10th International Histocompatibility Workshop. DQWa(DQw4) is strongly associated with insulin dependent diabetes mellitus (IDDM) and Vogt-Koyanagi-Harada syndrome in Japanese. Recently it was clarified that the susceptibility to IDDM has been determined by the amino acid residue of 57th position of DQ chain, that is the DQ antigen carrying aspartic acid at this position is resistant to IDDM and non-aspartic acid is susceptible. The base sequence analysis by using cloned DQWa gene revealed that DQWa carries aspartic acid at this particular position, although DQWa is strongly associated with IDDM in Japanese. Interestingly the DR4 which is strongly in linkage disequilibrium with DQWa is characteristic to Japanese and carries serine at 57th position of its chain, whereas most DR molecules carry aspartic acid. Surprisingly, more than 90% of Japanese IDDM patients carries non-aspartic acid at 57th position of their DR chain, usually homozygous state. These esults indicate that the susceptibility to IDDM has been determined by the amino acid residue of 57th position of DR chain in Japanese while DQ chain in Caucasian, and the mode of inheritance of susceptibility to IDDM is recessive.
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