| Project/Area Number |
04670396
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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 |
内科学一般
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| Research Institution | Juntendo University School of Medicine |
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Principal Investigator |
TAKASAKI Yoshinari Juntendo Univ.School of Medicine, Medicine, Associate professor, 医学部, 助教授 (80154772)
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| Co-Investigator(Kenkyū-buntansha) |
YAMANAKA Juntendo Univ.School of Medicine, Medicine, assistant professor, 医学部, 助手 (60230504)
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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 |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1994: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 1993: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1992: ¥800,000 (Direct Cost: ¥800,000)
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| Keywords | Autoantibody / Autoantigen / Ki antigen / Molecular mimicry / epitope / 抗核抗体 / ウイルス / ANA / cDNA / SLE / SV40large T antigen / 自時抗体 |
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| Research Abstract |
A cDNA coding for a nuclear autoantigen, Ki, has been cloned previously and we have found that Ki has an amino acid sequence which is homologous to SV 40 large T antigen nuclear localization sign (SV 40 NLS). We studied whether the amino acid sequence which is homologous to SV 40 NMS is one of the epitopes on Ki antigen and anti-Ki antibody croos-react with SV 40 large T antigen.
Forty-nine anti-Ki positive sera were selected from 250 patients with systemic lupus erythematosus (SLE) by enzyme-linked immunosorbent assay (ELISA) using recombinant Ki (bNAX) as an antigne. A 16-mer Ki synthetic peptide that had a sequence homologous to SV 40 NLS (KILT) was prepared. In addition, 4 different synthetic peptides (KISP1-4) were prepared based on the analysis of conformational profile and hydoropathy of Ki antigen. The reactivities of anti-Ki sera to those synthetic peptides were tested by ELISA.Eighteen out of 49 sera reacted with KILT but none of them strongly reacted with KISP1-4. The KILT specifically reacted with anti-Ki sera but did not react with autoantibodies to other nuclear antigens such as U1 RNP,Sm, SS-A,SS-B,PCNA,Scl-70 and Jo-1. In addition, the reactivity of anti-Ki antibodies to KILT was specifically inhibited by bNAX.Those results indicated that KILT specifically reacted with anti-Ki antibody. A 7-mer synthetic peptide that had the same sequence as that of SV 40 NLS (LTSP) was prepared to test the cross-reactivity between the Ki antigen and SV 40 large T antigen. Eight out of 49 sera reacted with it and 7 of them reacted with both LTSP and KILT.The frequency of sera reacted with LTSP in anti-KILT positive sera (38.8%) was significantly higher (P<0.01) compared with that in anti-KILT negative sera (3.2%). Those results suggest that anti-Ki antibodies from lupus patients recognize the amino acid sequence homologous to SV 40 NLS as an epitope and molecular mimicry between Ki and SV 40 large T antigen may play a possible role for autoantibody production.
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