| Project/Area Number |
08457157
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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 |
内科学一般
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| Research Institution | University of Tsukuba (1998)
St. Marianna University School of Medicine (1996-1997) |
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Principal Investigator |
SUMIDA Takayuki Department of Internal Medicine, University of Tsukuba, Professor, 臨床医学系内科, 教授 (00183054)
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| Project Period (FY) |
1996 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥7,300,000 (Direct Cost: ¥7,300,000)
Fiscal Year 1998: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1997: ¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1996: ¥3,400,000 (Direct Cost: ¥3,400,000)
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| Keywords | Sjogren's syndrome / T cell receptor / autoreactive T cell / T cell epitope / alpha-amylace / アナログペプチド / シェ-グレン症候群 / 自己抗原エポトープ / 自己抗原 / 自己免疫疾患 |
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| Research Abstract |
Analyses of T cell receptor (TCR) on T cells in labial salivary glands of patients with Sjogren's syndrome (SS) support the notion that infiltrating T cells were induced by antigen-driven rather than superantigen-driven stimulation. T cell epitopes recognized by T cells infiltrating in the labial salivary glands of SS patients have been clarified using different four strategies such as T cell lines, PCR-SSCP, West-Western, and TOP a/b transfectants methods. 1) Cell proliferative analysis by T cell lines from labial salivary glands showed T cell epitope (DEREQLRILG) at position AA203-21 2 of Ro/SS-A protein. 2) Analysis with SSCP and the synthetic peptides combinatorial libraries demonstrated that WAEILRIGRV (TORBV6S7) and WVNMLRRGI (HSP10/60) were suitable candidates for antigens. WAEILRIGRV (TOPBV6S7) reactive T cells could produce both IL-2 and IL-4, while WVNMLRRGI (HSP10/60) reactive T cells were able to produce only IL-2 in vitro. 3) West-Western analysis using TOR CDR3 protein from unique TOP in salivary glands clarified that human a-amylase salivary precursor (NPFRPWWERYQWPV, AA68-80 and EKMSYLKNWGEG, AA287-298) is a candidate for salivary glands-specific autoantigens in SS.In fact, 3 of 11 SS patients (27%) showed a-amylase reactive T cells in labial salivary glands. 4) A full-length cDNA encoding paired TOP a and b chains has been isolated from a single T cell in labial salivary glands of SS patient. In conclusion, a-amylase function as salivary glands-specific autoantigen, whereas Ro/SS-A 52kD, and HSP10/60 act as glands-non-specific autoantigens. Furthermore, some autoantigens such as Ro/SS-A 52kD and HSP1 0/60 are thought to be autoaggressive T cell epitopes in the generation of SS, although TCRBV6S7 might be aregulatory T cell epitope in SS.
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