1990 Fiscal Year Annual Research Report

がん抗原の発現調節と免疫系による認識

Research Project

Project/Area Number	02151014
Research Institution	Chiba University
Principal Investigator	谷口克千葉大学, 医学部, 教授 (80110310)
Co-Investigator(Kenkyū-buntansha)	藤原大美大阪大学, 医学部, 助教授 (70116094) 菅野純夫東京大学, 医科学研究所, 助手 (60162848) 森脇和郎国立遺伝研究所, 教授 (50000229) 西村泰治九州大学, 生防医研, 助教授 (10156119) 松岡雄治福岡大学, 医学部, 教授 (70078773)
Keywords	がん抗原 / 腫瘍抵抗性 / トランスフレ-ス遺伝子 / アンティセンス / 熱タンパク / 内在性レトロウィルス / がん関連抗原
Research Abstract	(1).がん遺伝子の活性化に伴なって発現されるがん抗原として内因性分子(HSP,内在ウイルスenv蛋白)を同定。これが腫瘍抵抗性に重要な分子であることを証明。一部はcDNAクロ-ン化成功,塩基配列決定している。これら遺伝子のプロモ-タ領域を用いたCATアツセイで腫瘍選択的な細胞因子の存在が示された(佐藤、谷口)。応用面で,担がん動物由来Mφを少量(4×10^6)移入するだけで正常個体に腫瘍抵抗性を賦与できた(藤原)。腫瘍抵抗性遺伝子が野生マウス第4染色体上に存在することを野生純系リコンビナント・マウスで証明した(森脇)。一方,ヒトDQトランスゲニック・マウスのT細胞レパトアと免疫能を調べヒトDQが十分に機能していることが判明(西村)。CD2分子を介するT細胞活性化は抗原受容体の存在と無関係に起ることが判りNK細胞活性化のメカニズムを明らかにした(斉藤)。(2)がん抗原としても重要な糖鎖構造の発現に重要なβ_<1ー4>ガラクトシルTFのゲノム遺伝子(70Kb)の全構造を決定。Exon6にUDP結合部が存在する事を決定(成松)。がん関連抗原のファミリ-であるNCA遺伝子群は12種存在し,多形核白血球上では接着分子として機能することが明らかとなった(松岡)。(3).脱分化をおこすのはantiーsense cmyc・sense cmyc複合体が74KbのDNA結合蛋白を誘導するためであることが判明。これらのcDNAのクロ-ン化に成功(横山)。温度感受性がんウィルスで株化した納若株から分化の初期のみに発現するテノム遺伝子をクロ-ン化した。成熟細胞では発現しなくなる膜蛋白で分化・脱分化と抗原発現の機序を知る良いモデル系である(竹森)。(4)タグ付き発現ベクタ-を開発した。ベクタ-の種類によって,核局在のもの,膜局在のものを区別してクロ-ン化できる。今後のがん遺伝子発現から抗原発現までの過程に関係する遺伝子の解柝に有力な武器となる(菅野)。

Research Products

(14 results)

All Other

All Publications (14 results)

[Publications] Harada,Y.,Sakatsume,M.& Taniguchi,M.: "Induction of antiーmelanoma cytotoxic and suppressor T cell in vitro by artifical antigen,FM3ーlactone,in mouse" Jpn,J.Cancer Res.81. 383-387 (1990)
[Publications] Tagawa,M.,Sakamoto,T.,Shigemoto,K.,Matsubara,H.,Tamura,Y.,Nakamura,I.,Okitsu,A.,Imai,K.& Taniguchi,M.: "Expression of novel DNAーbinding protein with zinc finger structure in various tumor cells." J.Biol.Chem.265. 20021-20026 (1990)
[Publications] Tada,T.,Sano,H.,Sato,S.,Shima,J.,Fujiwara,H.& Hamaoka,T.: "Immune dysfunction expressed selectively on L3T4^+ T cells in the tumorーbearing state." J.Leukocyte Biol.47. 149-157 (1990)
[Publications] Utsumi,K.,Takai,Y.,Tada,T.,Ohzeki,S.,Fujiwara,H.& Hamaoka,T.: "Enhanced production of interleukinー6 in tumorーbearing mice and determination of cells responsible for its augmented production." J.Immunol.145. 397-403 (1990)
[Publications] Kuroki,Mo.,Matsuo,Y.,Ohtani,T.,Minowada,J.,Kuroki,Ma.& Matsuoka,Y.: "A novel CEAーcrossーreacting antigen of molecular weight 140,000 expressed on human lymphoid cell lines." Molecular Immunology. 27. 689-696 (1990)
[Publications] Arakawa,F.,Kuroki,Mo.,Misumi,Y.,Oikawa,S.,Nakazato,H.& Matsuoka,Y.: "Characterization of a cDNA clone encoding a new species of the nonspecific crossーreacting antigen (NCA),a member of the CEA gene family." Biochem.Biophys.Res.Commun.166. 1063-1071 (1990)
[Publications] Nishimura,Y.,Iwanaga,T.,Inamitsu,T.,Yanagawa,Y.,Yasunami,M.,Kimura,A.,Hirokawa,K.& Sasazuki,T.: "Expression of human major histocompatibility complex,HLAーDQw6 genes alters the immune response in C57BL/6 mice." J.Immunol.145. 353-360 (1990)
[Publications] Suzuki,H.,Kurihara,Y.,Kanehisa,T.& Moriwaki,K.: "Variation in the distribution of silverーstaining nucleolar organizer regions on the chromosomes of the wild mouse,Mus musculus." Mol.Biol.Evol.7. 271-282 (1990)
[Publications] Torigoe,T.,Sato,N.,Cho,JーM.,Tsuboi,T.,Qi,W.,Kon,S.,Wada,Y.,Takahashi,N.& Kikuchi,K.: "Analisis of the expression of tumor rejection antigen of BALB3T3 cells transformed by the activated oncogenes by use of BRH19 monoclonal antibody." J.Immunol.(1991)
[Publications] Kim,D.W.,Uetsuki,T.,Kaziro,Y.,Yamaguchi,N.,& Sugano,S.: "Use of the human elongation factor 1 promoter as a versatile and efficient expression system." Gene.91. 217-223 (1990)
[Publications] Takemori,T.,Mizuguchi,J.,Miyazoe,I.,Kimoto,H.,Shigemoto,K.,Shirasawa,T.,Maruyama,N.& Taniguchi,M.: "Two types of μ chain complexes are expressed during the differentiation from preーB to mature B cells." EMBO J.9. 2493-2500 (1990)
[Publications] Ohno,H.,& Saito,T.: "CD3 ζ and η chains are produced by alternative splicing from a common gene." Int.Immunol.2. 1117-1119 (1990)
[Publications] Yokoyama,K.: "Transcriptional regulation of endogenous Myc protooncogene by antisense RNA.Prospects for antisense nucleic acid therapy of cancer and viral infection." Alan R.LISS, (1990)
[Publications] Yokoyama,K.: "Antisense RNA induces the nuclear transcription factor to repress the expression of endogeneous cーmyc.Antisense RNA and DNA." Alan R.LISS, (1990)

1990 Fiscal Year Annual Research Report

がん抗原の発現調節と免疫系による認識

Principal Investigator

谷口 克 千葉大学, 医学部, 教授 (80110310)

Research Products

[Publications] Harada,Y.,Sakatsume,M.& Taniguchi,M.: "Induction of antiーmelanoma cytotoxic and suppressor T cell in vitro by artifical antigen,FM3ーlactone,in mouse" Jpn,J.Cancer Res.81. 383-387 (1990)

[Publications] Tagawa,M.,Sakamoto,T.,Shigemoto,K.,Matsubara,H.,Tamura,Y.,Nakamura,I.,Okitsu,A.,Imai,K.& Taniguchi,M.: "Expression of novel DNAーbinding protein with zinc finger structure in various tumor cells." J.Biol.Chem.265. 20021-20026 (1990)

[Publications] Tada,T.,Sano,H.,Sato,S.,Shima,J.,Fujiwara,H.& Hamaoka,T.: "Immune dysfunction expressed selectively on L3T4^+ T cells in the tumorーbearing state." J.Leukocyte Biol.47. 149-157 (1990)

[Publications] Utsumi,K.,Takai,Y.,Tada,T.,Ohzeki,S.,Fujiwara,H.& Hamaoka,T.: "Enhanced production of interleukinー6 in tumorーbearing mice and determination of cells responsible for its augmented production." J.Immunol.145. 397-403 (1990)

[Publications] Kuroki,Mo.,Matsuo,Y.,Ohtani,T.,Minowada,J.,Kuroki,Ma.& Matsuoka,Y.: "A novel CEAーcrossーreacting antigen of molecular weight 140,000 expressed on human lymphoid cell lines." Molecular Immunology. 27. 689-696 (1990)

[Publications] Arakawa,F.,Kuroki,Mo.,Misumi,Y.,Oikawa,S.,Nakazato,H.& Matsuoka,Y.: "Characterization of a cDNA clone encoding a new species of the nonspecific crossーreacting antigen (NCA),a member of the CEA gene family." Biochem.Biophys.Res.Commun.166. 1063-1071 (1990)

[Publications] Nishimura,Y.,Iwanaga,T.,Inamitsu,T.,Yanagawa,Y.,Yasunami,M.,Kimura,A.,Hirokawa,K.& Sasazuki,T.: "Expression of human major histocompatibility complex,HLAーDQw6 genes alters the immune response in C57BL/6 mice." J.Immunol.145. 353-360 (1990)

[Publications] Suzuki,H.,Kurihara,Y.,Kanehisa,T.& Moriwaki,K.: "Variation in the distribution of silverーstaining nucleolar organizer regions on the chromosomes of the wild mouse,Mus musculus." Mol.Biol.Evol.7. 271-282 (1990)

[Publications] Torigoe,T.,Sato,N.,Cho,JーM.,Tsuboi,T.,Qi,W.,Kon,S.,Wada,Y.,Takahashi,N.& Kikuchi,K.: "Analisis of the expression of tumor rejection antigen of BALB3T3 cells transformed by the activated oncogenes by use of BRH19 monoclonal antibody." J.Immunol.(1991)

[Publications] Kim,D.W.,Uetsuki,T.,Kaziro,Y.,Yamaguchi,N.,& Sugano,S.: "Use of the human elongation factor 1 promoter as a versatile and efficient expression system." Gene.91. 217-223 (1990)

[Publications] Takemori,T.,Mizuguchi,J.,Miyazoe,I.,Kimoto,H.,Shigemoto,K.,Shirasawa,T.,Maruyama,N.& Taniguchi,M.: "Two types of μ chain complexes are expressed during the differentiation from preーB to mature B cells." EMBO J.9. 2493-2500 (1990)

[Publications] Ohno,H.,& Saito,T.: "CD3 ζ and η chains are produced by alternative splicing from a common gene." Int.Immunol.2. 1117-1119 (1990)

[Publications] Yokoyama,K.: "Transcriptional regulation of endogenous Myc protooncogene by antisense RNA.Prospects for antisense nucleic acid therapy of cancer and viral infection." Alan R.LISS, (1990)

[Publications] Yokoyama,K.: "Antisense RNA induces the nuclear transcription factor to repress the expression of endogeneous cーmyc.Antisense RNA and DNA." Alan R.LISS, (1990)

谷口克千葉大学, 医学部, 教授 (80110310)