| Project/Area Number |
04454209
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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 |
Immunology
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| Research Institution | Saga Medical School |
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Principal Investigator |
KIMOTO Masao Professor, Department of Immunology, Saga Medical School, 医学部, 教授 (40153225)
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| Project Period (FY) |
1992 – 1994
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| Project Status |
Completed (Fiscal Year 1994)
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| Budget Amount *help |
¥6,400,000 (Direct Cost: ¥6,400,000)
Fiscal Year 1994: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1993: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1992: ¥3,800,000 (Direct Cost: ¥3,800,000)
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| Keywords | T cell self-antigen epitope / B / WF1 mice / H-2 complex / Mixed haplotype / Class II molecule / Peptide motif / Auto-reactive T cell / 病原性T細胞クローン / 抗DNA抗原 / SCIDマウス / TCR / 自己ペプチド / 結合ペプチドモチーフ / T細胞クローン / 自己反応性 / BW / F1マウス / 自己抗原ペプチド / MHCクラスII分子 / ハプロタイプ混合クラスII分子 / 抗DNA抗体 |
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| Research Abstract |
(NZB x NZW) F1 (B/WF1) mice have been studied as an animal model of SLE,a human systemic auto-immune disease. The onset and/or progression of B/WF1 auto-immune symptoms is reported to involve auto-reactive T cells and to be critically related to the heterozygosity of H-2 complex, the murine major histocompatibility complex. We analyzed auto-reactive T cell clones derived from B/WF1 mice. Specificity analysis revealed the presence of mixed haplotype Abetaz/Aalphad class II molecule-restricted auto-reactive T cell clones in B/WF1 mice. Immunoprecipitation and SDS/PAGE analysis usign anti-class II monoclonal antibody revealed that the amount of Abetaz/Aalphad class II molecules is very low compared to conventional class II molecules. Some of the auto-reactive T cell clones induced lgG anti-DNA antibody production upon transfer to young pre-autoimmune B/WF1 mice. DNA sequence analysis of mutant lines derived from transfectant APC that express mutated Abetaz/Aalphad class II molecules revealed that the amino acid at position Aalphad69 is important for the antigen recognition of these auto-reactive T cells. Analysis of bound peptides obtained by HPLC fraction of eluted peptides from affinity purified Abetaz/Aalphad class II molecules revealed a major motif as (I,F)XXXX(M,F,Y).
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