Analysis of HLA class II genes and functional roles of their products regulating disease susceptibility
| Project/Area Number |
02454165
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Experimental pathology
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| Research Institution | Asahikawa Medical college |
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Principal Investigator |
KATAGIRI Makoto Asahikawa Medical College Professor, 医学部, 教授 (10041823)
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| Co-Investigator(Kenkyū-buntansha) |
SHIBATA Toshiya Asahikawa Medical College Instructor, 医学部, 助手 (50235579)
KAWABATA Isao Asahikawa Medical College Instructor, 医学部, 助手 (50195129)
MIYOKAWA Naoyuki Asahikawa Medical College Assistant Professor, 医学部, 講師 (20182058)
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| Project Period (FY) |
1990 – 1991
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| Project Status |
Completed (Fiscal Year 1991)
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| Budget Amount *help |
¥6,300,000 (Direct Cost: ¥6,300,000)
Fiscal Year 1991: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1990: ¥4,900,000 (Direct Cost: ¥4,900,000)
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| Keywords | HLA gene / HLA class II gene / Disease susceptibility / IDDM / Birch pollen allergy |
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| Research Abstract |
The developments of a certain, category of autoimmune diseases involve in the gene products of HLA class II as an etiologic factor. We have studied HLA class 11 genes and their products that was thought to be concerned in the development of insulin dependent diabetes mellitus (IDDM) or birch pollen allergy.
1. HLA-DR4/DQw4 and HLA-DR9/DQw9 haplotypes correlate to the development of IDDM in Japanese subjects. We have determined the whole nucleotide sequence of HLA-DQw9 genomic DNAs from a Japanese IDDM patient and his healthy sibling. These two sequences were completely identical. Next, we have determined the nucleotide sequence of the second exon of HLA-DQA1, -DQBl and -DRB1, which have been amplified with PCR, from 11 Japanese IDDM patients. The deduced amino acids of the position 57 of DQ beta chain were an aspartic acid. On the other hand, the deduced amino acids at the same position of DR beta chain were a non-aspartic acid at least on one haplotype. Our data suggested that DR beta
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chain preferentially contributed to the susceptibility of Japanese IDDM with attention to the important function of the position 57 of beta chain.
2. We have made L-DR9 or L-DQw9 transfectants that were transfected HLA-DR9A/-DR9B or ULA-DQw9A/-DQw9B genomic DNAs to the mouse L-cell. We have also made a B6-DR9 transgenic mouse that HLA-DRAL and -DR9BI DNAs were microinjected to oocyte of B6 mouse. This B6-DR9 transgenic mouse did not express DR antigen on the cell surface. However, IL-4 could induce DR9mRNA accumulation of DR gene and cell surface expression of DR antigen in this mouse.
3. HLA-DR9 and -DQw9 haplotypes correlate to the development of birch pollen allergy in Japanese subjects. The Japanese white birch pollen antigen that was extracted by ourselves induced LPR with lymphocytes from the pollen allergy patients. This LPR was inhibited by anti-HLA-DR antibody but not any anti-HLA-DQ antibodies. And T lymphocytes from patients proliferated only with pollen antigen and L-DR9, but not with pollen antigen and L-DQw9. Our data suggested that HLA-DR9 contributed the development of the birch pollen allergy and played an important role on the antigen presenting step to T lymphocyte activation. Less
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Report
(3 results)
Research Products
(24 results)
