1991 年度実績報告書

HLAクラスII遺伝子の異所性発現調節機構

研究課題

研究課題/領域番号	01480192
研究機関	九州大学
研究代表者	木村彰方九州大学, 生体防御医学研究所, 助手 (60161551)
研究分担者	西村泰治九州大学, 生体防御医学研究所, 助教授 (10156119) 笹月健彦九州大学, 生体防御医学研究所, 教授 (50014121)
キーワード	HLA / 遺伝的多型性 / プロモ-タ- / 発現制御 / 転写因子
研究概要	HLAーDQA1遺伝子の発現制御領域にはNFーTRSとNFーYの2種の核蛋白が結合するが、その結合領域は重複しており、しかもこの領域内に遺伝的多型性の存在することを明らかにした。さらに同領域の遺伝的多型性に対応する合成オリゴヌクレオチドプロ-ブを用いたゲルシフトアッセイにより、対立遺伝子特異的な塩基変異によるNFーTRSおよびNFーYとの結合親和性の著明な変化を認めた。すなわち、QAP4.1対立遺伝子(DQA10501に対応)、QAP4.2対立遺伝子(DQA10401および*0601に対応)では、これらの正の転写因子との結合親和性が極めて低いこと、NFーTRS結合領域内に変異を有するQAP3.1および3.2対立遺伝子においてはNFーYとの結合親和性も低下していた。以上よりNFーTRSとNFーYは協調してDQA1遺伝子プロモ-タ-に結合することが明かとなった。このことは、DQA1遺伝子の発現性に遺伝的多型性の存在する可能性を示唆するが、CATアッセイを用いた転写解析から、DQA1対立遺伝子毎にIFNやTNFによる発現誘導性に差の存在することがわかった。さらに若年性糖尿病とDQA1プロモ-タ-領域多型性の相関を検討したところ、QAP1.2および1.4対立遺伝子の著明な減少(相対危険率0.36)とQAP3.1対立遺伝子の著明な増加(相対危険率4.33)を認めた。一方、DRB1遺伝子の発現制御領域においても、正の転写因子NFーYおよびCTFそれぞれの結合領域に遺伝的多型性が確認され、合成オリゴヌクレオチドプロ-ブを用いた同様のゲルシフトアッセイにより、この遺伝的多型性と転写因子への結合親和性に密接な関連のあることが明かとなった。このことより、HLAクラスII遺伝子においては、発現性における遺伝的多型性が存在すると考えられ、自己免疫疾患発症機構への関与が推定された。

研究成果

(26件)

すべてその他

すべて文献書誌 (26件)

[文献書誌] Kamikawaji,N.,Fujisawa,K.,Yoshizumi,H.,Fukunaga,M.,Yasunami,M.,Kimura,A.,Nishimura,Y.,Sasazuki,T.: "HLAーDQ restricted CD4^+ T cells specific to streptococcal antigen exist in low responders but not in high responders." Journal of Immunology. 146. 2560-2567 (1991)
[文献書誌] Fujisawa,K.,Kamikawaji,N.,Yasunami,M.,Kimura,A.,Nishimura,Y.,Sasazuki,T.: "High precursor frequency of human T cells reactive to HLAーDQ molecules expressed on mouse L cell transfectants." European Journal of Immunology. 21. 2341-2347 (1991)
[文献書誌] Nishimura,Y.,Kamikawaji,N.,Fujisawa,K.,Yoshizumi,H.,Yasunami,M.,Kimura,A.,Sasazuki,T.: "Genetic control of immune response and disease susceptibility by the HLAーDQ gene." Research in Immunology. 142. 459-466 (1991)
[文献書誌] Tamaki,K.,Yamamoto,T.,Uchihi,R.,Katsumata,Y.,Kondo,K.,Mizuno,S.,Kimura,A.,Sasazuki,T.: "Frequency of HLAーDQA1 alleles in the Japanese population" Human Heredidy. 41. 209-214 (1991)
[文献書誌] Dong,R.P.,Kimura,A.,Numano,F.,Nishimura,Y.,Sasazuki,T.: "HLAーlinked susceptibility and resistance to Takayasu arteritis." Heart and Vessels.
[文献書誌] Dong,R.P.,Kimura,A.,Sasazuki,T.: "Sequence analysis of three novel DRw14ーDRB1 alleles." Immunogenetics.
[文献書誌] Dong,R.P.,Kimura,A.,Numano,F.,Yajima,M.,Hashimoto,Y.,Kishi,Y.,Nishimura,Y.,Sasazuki,T.: "HLAーDP antigen and Takayasu arteritis" Tissue Antigens.
[文献書誌] Hatae,K.,Kimura,A.,Okubo,R.,Watanabe,H.,Erlich,H.,Ueda,K.,Nishimura,Y.,Sasazuki,T.: "Genetic control of nonーimmune responsiveness to hepatitis B virus vaccine by an extended HLA haplotype." European Journal of Immunology.
[文献書誌] Hoshino,S.,Kimura,A.,Fukuda,Y.,Dohi,K.,Sasazuki,T.: "PCRーSSCP analysis of polymorphisms in DPA1 and DPB1 genes:a simple,economical and rapid method for histocompatibility testing." Human Immunology.
[文献書誌] Senju,S.,Kimura,A.,Yasunami,M.,Kamikawaji,N.,Yoshizumi,H.,Nishimura,Y.,Sasazuki,T.: "Alleleーspecific expression of the cytoplasmic exon of HLAーDQB1 gene" Immunogenetics.
[文献書誌] Kimura,A.,Dong,R.P.,Harada,H.,Sasazuki,T.: "DNA typing of HLA class II genes in Bーlymphoblastoid cell lines homozygous for HLA" Tissue Antigens.
[文献書誌] Nishi,H.,Kimura,A.,Fukuda,S.,Kusukawa,R.,Kawamura,K.,Nimura,Y.,Nagano,M.,Yasuda,H.,Kawai,C.,Sugimoto,T.,Okada,R.,Yazaki,Y.,Tanaka,H.,Harumi,K.,Koga,Y.,Sasazuki,T.,Toshima,H.: "Genetic analysis of dilated cardiomyopathy:HLA and immunoglobulin genes may confer susceptibility" Japanese Circulation Journal.
[文献書誌] Fukui,Y.,Esaki,Y.,Yasunami,M.,Kimura,K.,Hirokawa,K.,Nishimura,Y.,Sasazuki,T.: "T cell repertoire and selfーtolerance in the transgenic mice with HLAーDRA on X chromosome.in"HLA 1991 Vol.II"eds.Sasazuki,T.,Aizawa,M.,Tsuji,K." Oxford University Press,Oxford, (1992)
[文献書誌] Esaki,Y.,Fukui,Y.,Yasunami,M.,Kimura,A.,Hirokawa,K.,Nishimura,Y.,Sasazuki,T.: "Functional expression of HLAーDQw4 genes in a line of transgenic C57BL/6 mouse.in"HLA 1991 Vol.II"eds.Sasazuki,T.,Aizawa,M.,Tsuji,K." Oxford University Press,Oxford, (1992)
[文献書誌] Kimura,A.,Sasazuki,T.: "Organization and design of the DNA component of the 11th HLA Workshop.in"HLA 1991 Vol.I"eds.Tsuji,K.,Aizawa,M.,Sasazuki,T." Oxford University Press,Oxford, (1992)
[文献書誌] Nishimura,Y.,Kamikawaji,N.,Fujisawa,K.,Yoshizumi,H.,Yasunami,M.,Kimura,A.,Sasazuki,T.: "Contribution of the HLAーDQ gene in controling immune response and disease susceptibility.in"Molecular Approaches to the Study and Treatment of Human Diseases"eds.Yoshida,T.O.&Wilson,J.M." Elsevier Science Publisher, (1992)
[文献書誌] Kimura,A.,Sasazuki,T.: "HLAーDQA gene is differently regulated from other HLA class II genes.in"Molecular Approaches to the Study and treatment of Human Diseases"eds.Yoshida,T.O.&Wilson,J.M." Elsevier Science Publisher, (1992)
[文献書誌] Kimura,A.,Sasazuki,T.: "Polymorphism in the 5' fleaking region of DQAI gene and its relation to DRーDQ haplotype.in"HLA 1991 Vol.II"eds.Sasazuki,T.,Aizawa,M.,Tsuji,K" Oxford University Press,Oxford, (1992)
[文献書誌] Kimura,A.,Hoshino,S.,Yoshida,M.,Sasazuki,T.: "PCRーSSCP analysis of HLA class II genes.in"HLA 1991 Vol.I"eds.Tsuji,K.,Aizawa,M.,Sasazuki,T." Oxford University Press,Oxford, (1992)
[文献書誌] Kimura,A.,Sasazuki,T.: "Epitope analysis of workshop panels:combined study of oligotyping and serological typing in"HLA 1991 Vol.I"eds.Tsuji,K.,Aizawa,M.,Sasazuki,T." Oxford University Press,Oxford, (1992)
[文献書誌] Yoshida,M.,Kimura,A.,Numano,F.,and Sasazuki,T.: "DNA typing of HLAーB antigens by PCR method.in"HLA 1991 Vol.II"eds.Sasazuki,T.,Aizawa,M.,Tsuji,K." Oxford University Press,Oxford, (1992)
[文献書誌] Ogawara,S.,Kimura,A.,Michinaga,I.,Naito,S.,Sasazuki,T.,and Arakawa,K.: "Nucleotide sequences of DRBX pseudogene linked to HLAーDRw15 haplotypes.in"HLA 1991 Vol.II"eds.Sasazuki,T.,Aizawa,M.,Tsuji,K." Oxford University Press,Oxford, (1992)
[文献書誌] Hamaguchi,K.,Kimura,A.,Dong,RーP.,Noda,N.,Okeda,T.,Chikuba,N.,Fujishima,M.,Nagataki,S.,Takaki,R.,and Sasazuki,T.: "Specific combination of HLA DRB and DQB alleles confer susceptibility,while DQB gene determined resistance to IDDM in Japanese.in"HLA 1991 Vol.II"eds.Sasazuki,T.,Aizawa,M.,Tsuji,K." Oxford University Press,Oxford, (1992)
[文献書誌] Tsuchiya,K.,Kondo,M.,Kimura,A.,Nishimura,Y.,and Sasazuki,T.: "DRB1 and/or DQB1 locus control susceptibility and DRB1 controls resistance to RA.in"HLA 1991 Vol.II"eds.Sasazuki,T.,Aizawa,M.,Tsuji,K." Oxford University Press,Oxford, (1992)
[文献書誌] Kamikawaji,N.,Yoshizumi,H.,Mori,K.,Fujita,Y.,Kimura,A.,Nishimura,Y.,and Sasazuki,T.: "Identification of T cell epitopes in M protein from group A streptococcus.in"HLA 1991 Vol.II"eds.Sasazuki,T.,Aizawa,M.,Tsuji,K." Oxford University Press,Oxford, (1992)
[文献書誌] Juji,T.,Akaza,T.,Tokunaga,K.,Miyoshi,H.,Kashiwase,K.,Kimura,A.,and Sasazuki,T.: "Correlation analysis between serology and DNA typing.in"HLA 1991 Vol.I"eds.Tsuji,K.,Aizawa,M.,Sasazuki,T." Oxford University Press,Oxford, (1992)

1991 年度 実績報告書

HLAクラスII遺伝子の異所性発現調節機構

研究代表者

木村 彰方 九州大学, 生体防御医学研究所, 助手 (60161551)

研究成果

[文献書誌] Kamikawaji,N.,Fujisawa,K.,Yoshizumi,H.,Fukunaga,M.,Yasunami,M.,Kimura,A.,Nishimura,Y.,Sasazuki,T.: "HLAーDQ restricted CD4^+ T cells specific to streptococcal antigen exist in low responders but not in high responders." Journal of Immunology. 146. 2560-2567 (1991)

[文献書誌] Fujisawa,K.,Kamikawaji,N.,Yasunami,M.,Kimura,A.,Nishimura,Y.,Sasazuki,T.: "High precursor frequency of human T cells reactive to HLAーDQ molecules expressed on mouse L cell transfectants." European Journal of Immunology. 21. 2341-2347 (1991)

[文献書誌] Nishimura,Y.,Kamikawaji,N.,Fujisawa,K.,Yoshizumi,H.,Yasunami,M.,Kimura,A.,Sasazuki,T.: "Genetic control of immune response and disease susceptibility by the HLAーDQ gene." Research in Immunology. 142. 459-466 (1991)

[文献書誌] Tamaki,K.,Yamamoto,T.,Uchihi,R.,Katsumata,Y.,Kondo,K.,Mizuno,S.,Kimura,A.,Sasazuki,T.: "Frequency of HLAーDQA1 alleles in the Japanese population" Human Heredidy. 41. 209-214 (1991)

[文献書誌] Dong,R.P.,Kimura,A.,Numano,F.,Nishimura,Y.,Sasazuki,T.: "HLAーlinked susceptibility and resistance to Takayasu arteritis." Heart and Vessels.

[文献書誌] Dong,R.P.,Kimura,A.,Sasazuki,T.: "Sequence analysis of three novel DRw14ーDRB1 alleles." Immunogenetics.

[文献書誌] Dong,R.P.,Kimura,A.,Numano,F.,Yajima,M.,Hashimoto,Y.,Kishi,Y.,Nishimura,Y.,Sasazuki,T.: "HLAーDP antigen and Takayasu arteritis" Tissue Antigens.

[文献書誌] Hatae,K.,Kimura,A.,Okubo,R.,Watanabe,H.,Erlich,H.,Ueda,K.,Nishimura,Y.,Sasazuki,T.: "Genetic control of nonーimmune responsiveness to hepatitis B virus vaccine by an extended HLA haplotype." European Journal of Immunology.

[文献書誌] Hoshino,S.,Kimura,A.,Fukuda,Y.,Dohi,K.,Sasazuki,T.: "PCRーSSCP analysis of polymorphisms in DPA1 and DPB1 genes:a simple,economical and rapid method for histocompatibility testing." Human Immunology.

[文献書誌] Senju,S.,Kimura,A.,Yasunami,M.,Kamikawaji,N.,Yoshizumi,H.,Nishimura,Y.,Sasazuki,T.: "Alleleーspecific expression of the cytoplasmic exon of HLAーDQB1 gene" Immunogenetics.

[文献書誌] Kimura,A.,Dong,R.P.,Harada,H.,Sasazuki,T.: "DNA typing of HLA class II genes in Bーlymphoblastoid cell lines homozygous for HLA" Tissue Antigens.

[文献書誌] Fukui,Y.,Esaki,Y.,Yasunami,M.,Kimura,K.,Hirokawa,K.,Nishimura,Y.,Sasazuki,T.: "T cell repertoire and selfーtolerance in the transgenic mice with HLAーDRA on X chromosome.in"HLA 1991 Vol.II"eds.Sasazuki,T.,Aizawa,M.,Tsuji,K." Oxford University Press,Oxford, (1992)

[文献書誌] Esaki,Y.,Fukui,Y.,Yasunami,M.,Kimura,A.,Hirokawa,K.,Nishimura,Y.,Sasazuki,T.: "Functional expression of HLAーDQw4 genes in a line of transgenic C57BL/6 mouse.in"HLA 1991 Vol.II"eds.Sasazuki,T.,Aizawa,M.,Tsuji,K." Oxford University Press,Oxford, (1992)

[文献書誌] Kimura,A.,Sasazuki,T.: "Organization and design of the DNA component of the 11th HLA Workshop.in"HLA 1991 Vol.I"eds.Tsuji,K.,Aizawa,M.,Sasazuki,T." Oxford University Press,Oxford, (1992)

[文献書誌] Kimura,A.,Sasazuki,T.: "HLAーDQA gene is differently regulated from other HLA class II genes.in"Molecular Approaches to the Study and treatment of Human Diseases"eds.Yoshida,T.O.&Wilson,J.M." Elsevier Science Publisher, (1992)

[文献書誌] Kimura,A.,Sasazuki,T.: "Polymorphism in the 5' fleaking region of DQAI gene and its relation to DRーDQ haplotype.in"HLA 1991 Vol.II"eds.Sasazuki,T.,Aizawa,M.,Tsuji,K" Oxford University Press,Oxford, (1992)

[文献書誌] Kimura,A.,Hoshino,S.,Yoshida,M.,Sasazuki,T.: "PCRーSSCP analysis of HLA class II genes.in"HLA 1991 Vol.I"eds.Tsuji,K.,Aizawa,M.,Sasazuki,T." Oxford University Press,Oxford, (1992)

[文献書誌] Kimura,A.,Sasazuki,T.: "Epitope analysis of workshop panels:combined study of oligotyping and serological typing in"HLA 1991 Vol.I"eds.Tsuji,K.,Aizawa,M.,Sasazuki,T." Oxford University Press,Oxford, (1992)

[文献書誌] Yoshida,M.,Kimura,A.,Numano,F.,and Sasazuki,T.: "DNA typing of HLAーB antigens by PCR method.in"HLA 1991 Vol.II"eds.Sasazuki,T.,Aizawa,M.,Tsuji,K." Oxford University Press,Oxford, (1992)

[文献書誌] Ogawara,S.,Kimura,A.,Michinaga,I.,Naito,S.,Sasazuki,T.,and Arakawa,K.: "Nucleotide sequences of DRBX pseudogene linked to HLAーDRw15 haplotypes.in"HLA 1991 Vol.II"eds.Sasazuki,T.,Aizawa,M.,Tsuji,K." Oxford University Press,Oxford, (1992)

[文献書誌] Tsuchiya,K.,Kondo,M.,Kimura,A.,Nishimura,Y.,and Sasazuki,T.: "DRB1 and/or DQB1 locus control susceptibility and DRB1 controls resistance to RA.in"HLA 1991 Vol.II"eds.Sasazuki,T.,Aizawa,M.,Tsuji,K." Oxford University Press,Oxford, (1992)

[文献書誌] Kamikawaji,N.,Yoshizumi,H.,Mori,K.,Fujita,Y.,Kimura,A.,Nishimura,Y.,and Sasazuki,T.: "Identification of T cell epitopes in M protein from group A streptococcus.in"HLA 1991 Vol.II"eds.Sasazuki,T.,Aizawa,M.,Tsuji,K." Oxford University Press,Oxford, (1992)

[文献書誌] Juji,T.,Akaza,T.,Tokunaga,K.,Miyoshi,H.,Kashiwase,K.,Kimura,A.,and Sasazuki,T.: "Correlation analysis between serology and DNA typing.in"HLA 1991 Vol.I"eds.Tsuji,K.,Aizawa,M.,Sasazuki,T." Oxford University Press,Oxford, (1992)

1991 年度実績報告書

木村彰方九州大学, 生体防御医学研究所, 助手 (60161551)