1998 年度実績報告書

免疫識別と応答の多様性の分子機構

研究課題

研究課題/領域番号	08282104
研究機関	熊本大学
研究代表者	西村泰治熊本大学, 医学研究科教授 (10156119)
研究分担者	福井宣規九州大学, 生体防御医学研究所, 助手 (60243961) 稲葉カヨ京都大学, 理学部, 助教授 (00115792) 武田俊一京都大学, 医学研究科, 教授 (60188191) 吉開泰信名古屋大学, 医学部, 教授 (90158402) 笠原正典総合研究大学大学院, 先導科学研究科, 教授 (30241318)
キーワード	MHC / T細胞 / 抗原提示細胞 / 抗原ペプチド / 抗原提示 / T細胞活性化 / T細胞分化 / MHCの進化
研究概要	本研究は、抗原提示およびT細胞の抗原識別と多様な応答を解析し、免疫病の病因解析に供することを目的とする。今年度は以下の研究成果を得た。 1) ヒトCD4^+細胞のTCRアゴニストとアンタゴニストが誘導する細胞内Ca^<2+>応答に関わるシグナル伝達系は異なることを明らかにした。インバリアント鎖のCLIP部分を抗原ペプチドに置換した遺伝子を用いて、HLA-DR拘束性に抗原ペプチドを効率よくCD4^+細胞に提示するシステムを開発した(西村)。 2) 未熟な樹状細胞は、死細胞を貪食・分解してできた抗原ペプチドをMHCクラスII分子に結合して特異的T細胞に非常に効率よく提示することを示した(稲葉)。 3) MHCの染色体重複モデルに基づき、第3のVAV遺伝子をヒト第1染色体上のMHC領域と相同な領域に発見した。プロテアソーム・アクチベーターPA28複合体をコードするマウス遺伝子フェミリーを単離し、全構造を決定した(笠原)。 4) マウスのサルモネラ感染症で増加するNK1.1^+γδT細胞が自己MHCクラスIIをペプチド非依存性に認識し、N多様性を示す単一のVγ2/Vδ5を発現して胸腺で正の選択を受けることを明らかにした(吉開)。 5) 昨年度の研究で明らかにしたMHCクラスIおよびIIの両方に反応するT細胞クローンが、2種類のTCRα鎖を発現することに起因するか否か検討するために、H-2^b,TCRα鎖十/-,クラスII-/-マウスを作成した(武田)。 6) 単一のMHC・ペプチド複合体を発現するマウスが、末梢神経に自己免疫疾患を発症することを発見した。またTCRβ鎖を固定した同マウスのCD4^+8^-胸腺細胞に発現するTCRα鎖を解析し、正の選択における特異的TCR-ペプチド相互作用の関与を示した(福井)。

研究成果
(55件)

すべてその他

すべて文献書誌 (55件)

[文献書誌] Chen,Y-Z.: "Modulation of calacium response by altered peptide ligands in a human T cell clone." Eur.J.Immunol.28. 3929-3939 (1998)
[文献書誌] Fujita,H.: "Evidence that HLA class II-restricted human CD4^+ T-cells specific to p53 self peptides respond to p53 proteins of both wild and mutant forms." Eur.J.Immunol.28. 305-316 (1998)
[文献書誌] Yasukawa,M.: "CD4^+ cytotoxic T-cell clones specific for bcr-abl b3a2 fusion peptide augment colony fomation by chronic myelogenous leukemia cells in a b3a2-specific and HLA-DR-restricted manner." Blood. 92. 3355-3361 (1998)
[文献書誌] Ito,H.: "HLA-DP -associated susceptibility to optico spinal from of multiple sclerosis in the Japanese." Tissue Antigens. 52. 179-182 (1998)
[文献書誌] Ono,T.: "Molecular analysis of HLA class I(HLA-A and -B)and HLA class II(HLA-DRB1) genes in Japanese patients with multiple sclerosis(Western type and asian type)." Tissue Antigens. 52. 539-542 (1998)
[文献書誌] Oiso,M.: "Differential binding of peptides substituted at a putative C-terminal anchor residue to I-A^<7b56His57Ser> and I-A^<g7b56Pro57Asp>" Immunogenetics. 47. 411-414 (1998)
[文献書誌] Fujii,S.: "The CLIP-substituted invariant chain efficiently targets an antigenic peptide to HLA class II pathway in L cell." Human Immunol.59. 607-614 (1998)
[文献書誌] Tabata,H.: "Characterization of self-glutamic acid decarboxylase 65-reactive CD4^+ T cell clones established from Japanese patients with insulin dependent diabetes mellitus." Human Immunol.59. 549-560 (1998)
[文献書誌] Tanaka,Y.: "Efficient induction CD4^+ T cell lines reactive with a self-K-ras-derived peptide in vitro,using a mAb to CD29." Human Immunol.52. 179-182 (1998)
[文献書誌] Ohyama,H.: "Human T cell responses to 53-kDa outer membrane protein of Porphyromanas gingivalis in early-onset periodontitis patients." Human Immunol.59. 635-643 (1998)
[文献書誌] Zeki,K.: "Inducation of expression of MHC-class-II antigen on human thyroid carcinoma by wild-type p53." Int.J.Cancer. 75. 391-395 (1998)
[文献書誌] Hashimoto,H.: "HLA-DRB1 alleles and b2 glycoprotein I-dependent anticardiolipin antibodies in Japanese patients with systemic Jupus erythematosus." Clin.Exp.Rheumatol.16. 423-427 (1998)
[文献書誌] Sadanaga,Y.: "HLA class II association with Type I a;;ergy to house dust mite and Japanese cedar pollen in Japanese subjects." Allergology International. 47. 285-291 (1998)
[文献書誌] Nishimura,Y.: "(Review)Peptide-based molecular analyses of HLA class II -associated susceptibility to autoimmune dieases." Int.Rev.Immunol.(in press). (1999)
[文献書誌] Nishimura,Y.: "(Review)Modification of human T cell responses by altered peptide ligands:a new approach to antigen-specific modification" Internal Medicine. 37. 804-817 (1998)
[文献書誌] Nishimura,Y.: "(Review)Molecular analyses of HLA class II -associated susceptibility to subtypes of autoimmune diseases unique to Asians" Internatl.J.Cardiol.66(1). S93-S104 (1998)
[文献書誌] Inaba,K.: "Efficient presentation of phagocytosed cellular fragments on the MHC class II products of dendritic cells." J.Exp.Med.188(11). 2163-2173 (1998)
[文献書誌] steinman,R.M.: "Myeloid dendritic cells." J.Leukocyte Biol.in press. (1998)
[文献書誌] Kohda,K.: "characterization of the mouse PA28 activator complex gene family:Complete organizations of the three member genes and a physical map of the 〜150-kb region containing the α- and β-subunit genes." J.Immunol.160. 4923-4935 (1998)
[文献書誌] Tanaka,K.: "The MHC class I ligand generating system:Roles of immunoproteasomes and the interferon-g-inducible proteasome activator PA28." Immunol.Rev.163. 161-176 (1998)
[文献書誌] Suto.Y.: "Gene arrangement of the killer cell inhibitory receptor family on human chromosome 19q13.4 detected by fiber-FISH." Immunogenetics. 48. 235-241 (1998)
[文献書誌] Kasahara.M.: "What do the paralogous regions in the genome tell us about the origin of the adaptive immune system?" Immunol.Rev.166. 159-175 (1998)
[文献書誌] Kasahara,M.: "the chromosomal duplication model of the major histocompatibility compex." Immunol.Rev.(in press). (1998)
[文献書誌] Kasahara,M.: "Genome paralogy:A new perspective on the organization and origin of the major histocompatibility complex." Curr.Top.Microbiol.Immuno;.(in press). (1999)
[文献書誌] Kimura,Y.: "The regulatory role of heat shock protein 70-reactive CD4+T cells during rat listeriosis." Int.Immunol.10. 117-130 (1998)
[文献書誌] Sakai,T.: "Interleukin 15 activity in the intestinal mucosa of inflammatory bowel disease." Gastroenterology. 114. 1237-1243 (1998)
[文献書誌] Takano,M.: "Dibutyryl cyclic adenosine monophosphate protects mice against tumor necrosis factor-a-induced hepatocyte apoptosis accompanied by increased heat shock protein 70 expression." Cell Stress & Chaperones. 3. 109-117 (1998)
[文献書誌] Washizu,J.: "NF-kB binding site is essential for transcriptional activation of IL-15." Immunogenetics. 48. 1-7 (1998)
[文献書誌] Murosaki,S.: "Heat-killed Lactobacillus plantarum L-137 suppresses naturally fed antigen-specific IgE production by stimulation of IL-12 production in mice." J.Allergy Clin.Immunol.102. 57-64 (1998)
[文献書誌] Takano,M.: "A protective role of IL-15-dependent gd T cells in Escherichia coli infection in mice." Infect.Immun.66. 3270-3278 (1998)
[文献書誌] Takano,M.: "Prostaglandin E2 protects against liver injury after Escherichia coli infection but hampers the resolution of the infection in mice." J.Immunol.161. 3019-3025 (1998)
[文献書誌] Hirose,K.: "Interleukin-15 might be responsible early activation of intraepithelial lynphocytes after oral infection with Listeria monocytogenes in rats." Infect.Immun.66. 6577-5683 (1998)
[文献書誌] Yamada,K.: "Characterization of CD4+ CD8aa+ and CD4- CD8aa- intestinal intraepithelial lymphocytes in rats." Int.Immunol.11. 21-28 (1999)
[文献書誌] Nishimura,H.: "MHC class II-dependent NK1.1+gd T cells are induced in mice by Salmonella infection." J.Immunol.(in press). (1999)
[文献書誌] Mayumi,T.: "IL-15 is elevated in the patients of postoperative enterocllitis." Cytokine. (in press). (1999)
[文献書誌] Kimura,K.: "Immunogene therapy for murine fibrosarcoma using IL-15 gene with high translation efficiency." Eur.J.Immunol.(in press). (1999)
[文献書誌] Ishigami,M.: "The roles of intrahepatic Va 14+Nk1.1+T cells for liver injury induced by Salmonella infection." Hepatology. (in press). (1999)
[文献書誌] Ishigami,M.: "The roles of intrahepatic gd-Tcells for liver injury in mouse induced by Salmonella infection." Microbiol.Immunol.(in press). (1999)
[文献書誌] Hasegawa,T.: "Oral administration of hot water extracts of Chlorella vulgaris reduces IgE production against milk casein in mice." Int.J.Immunopharmacol.(in press). (1999)
[文献書誌] Murosaki,S.: "Immunopotentiating activity of nigerooligosaccharides for T helper 1-like immune response in mice." Biosci.Biotechnol.Biochem.(in press). (1999)
[文献書誌] Mitani,A.: "Interleukin-15 might be responsible for early activation of intestinal intraepithelial lymphocytes after oral infection with Listeria monocytogenes in mice." Immunolgy. (in press). (1999)
[文献書誌] Hirose,K.: "IL-15 might be responsibel for early protection by natural killer cells against infection with avirulent strain of Salmonella cholerasuis mice." J.Leuco.Biol.(in press). (1999)
[文献書誌] Shimokata,T.: "Bystander suppression of natirally fed antigen-specific IgE response by systemic asministration of unrelated antigen." J.Immunol.(in press). (1999)
[文献書誌] Sonoda,E.: "Rad51 deficient vertebrate cells accumulate chromosomal breaks prior to cell death." EMBOJ.17. 598-608 (1998)
[文献書誌] Takata,M.: "Homologous recombination and nonhomologous end joining pathways of DNA double-strand break repair have oberlapping roles in the maintenance of chromosomal integrity in vertebrate cells." EMBOJ.17. 5497-5508 (1998)
[文献書誌] Nishimura,H.: "MHC class II-dependent NK1.1= = cells are induced in mice by Salmonella infection." J.Immunol.(in press). (1999)
[文献書誌] Sano,t.: "Spontaneous clusterin of Thy-1 antigens on CD4+CD8+ thymocytes lacking TCR engagement by MHC/peptide complexes." Eur.J.Immunol.(in press). (1999)
[文献書誌] Gyotoku,T.: "An endogeneously processed self peptide and the corresponding exogenous peptide bound to the same MHC class II molecule could be distinct ligands for TCR with different kinetic stability." Eur.J.Immunol.(in press). (1999)
[文献書誌] Fukui,Y.: "Highly restricted T cell repertoire shaped by a sible MHC/peptide ligand in the presence of signal rearranged T cell receptor beta chain." J.Exp.Med.188. 897-907 (1999)
[文献書誌] Gapin,L.: "Quantitative analysis of the T-cell reperotire by a signal peptide/MHC complex." J.Exp.Med.187. 1871-1883 (1999)
[文献書誌] Takahashi,A.: "Development of peptide vaccines inducing production of neurtralizing antibodies against HIV-I viruses in HLA-DQ6 mice." Vaccine. 16. 1537-1543 (1999)
[文献書誌] 西村泰治: "「免疫遺伝学」医科遺伝学" 南山堂(印刷中),
[文献書誌] 西村泰治: "「MHCの構造と機能:抗原のプロセッシングとT細胞への抗原提示の機構」分子予防医学" 医学書院(印刷中),
[文献書誌] 西村泰治: "「抗原ペプチドのアナログを用いたヒトT細胞の抗原認識と活性化機構の解析」第21回阿蘇シンポジウム" 南山堂(印刷中),
[文献書誌] 入江厚: "「T細胞とMHCの相互作用」免疫しくみと疾患のすべて" 羊土社, 13 (1998)

1998 年度 実績報告書

免疫識別と応答の多様性の分子機構

研究代表者

西村 泰治 熊本大学, 医学研究科教授 (10156119)

研究成果

[文献書誌] Chen,Y-Z.: "Modulation of calacium response by altered peptide ligands in a human T cell clone." Eur.J.Immunol.28. 3929-3939 (1998)

[文献書誌] Fujita,H.: "Evidence that HLA class II-restricted human CD4^+ T-cells specific to p53 self peptides respond to p53 proteins of both wild and mutant forms." Eur.J.Immunol.28. 305-316 (1998)

[文献書誌] Yasukawa,M.: "CD4^+ cytotoxic T-cell clones specific for bcr-abl b3a2 fusion peptide augment colony fomation by chronic myelogenous leukemia cells in a b3a2-specific and HLA-DR-restricted manner." Blood. 92. 3355-3361 (1998)

[文献書誌] Ito,H.: "HLA-DP -associated susceptibility to optico spinal from of multiple sclerosis in the Japanese." Tissue Antigens. 52. 179-182 (1998)

[文献書誌] Ono,T.: "Molecular analysis of HLA class I(HLA-A and -B)and HLA class II(HLA-DRB1) genes in Japanese patients with multiple sclerosis(Western type and asian type)." Tissue Antigens. 52. 539-542 (1998)

[文献書誌] Oiso,M.: "Differential binding of peptides substituted at a putative C-terminal anchor residue to I-A^<7b56His57Ser> and I-A^<g7b56Pro57Asp>" Immunogenetics. 47. 411-414 (1998)

[文献書誌] Fujii,S.: "The CLIP-substituted invariant chain efficiently targets an antigenic peptide to HLA class II pathway in L cell." Human Immunol.59. 607-614 (1998)

[文献書誌] Tabata,H.: "Characterization of self-glutamic acid decarboxylase 65-reactive CD4^+ T cell clones established from Japanese patients with insulin dependent diabetes mellitus." Human Immunol.59. 549-560 (1998)

[文献書誌] Tanaka,Y.: "Efficient induction CD4^+ T cell lines reactive with a self-K-ras-derived peptide in vitro,using a mAb to CD29." Human Immunol.52. 179-182 (1998)

[文献書誌] Ohyama,H.: "Human T cell responses to 53-kDa outer membrane protein of Porphyromanas gingivalis in early-onset periodontitis patients." Human Immunol.59. 635-643 (1998)

[文献書誌] Zeki,K.: "Inducation of expression of MHC-class-II antigen on human thyroid carcinoma by wild-type p53." Int.J.Cancer. 75. 391-395 (1998)

[文献書誌] Hashimoto,H.: "HLA-DRB1 alleles and b2 glycoprotein I-dependent anticardiolipin antibodies in Japanese patients with systemic Jupus erythematosus." Clin.Exp.Rheumatol.16. 423-427 (1998)

[文献書誌] Sadanaga,Y.: "HLA class II association with Type I a;;ergy to house dust mite and Japanese cedar pollen in Japanese subjects." Allergology International. 47. 285-291 (1998)

[文献書誌] Nishimura,Y.: "(Review)Peptide-based molecular analyses of HLA class II -associated susceptibility to autoimmune dieases." Int.Rev.Immunol.(in press). (1999)

[文献書誌] Nishimura,Y.: "(Review)Modification of human T cell responses by altered peptide ligands:a new approach to antigen-specific modification" Internal Medicine. 37. 804-817 (1998)

[文献書誌] Nishimura,Y.: "(Review)Molecular analyses of HLA class II -associated susceptibility to subtypes of autoimmune diseases unique to Asians" Internatl.J.Cardiol.66(1). S93-S104 (1998)

[文献書誌] Inaba,K.: "Efficient presentation of phagocytosed cellular fragments on the MHC class II products of dendritic cells." J.Exp.Med.188(11). 2163-2173 (1998)

[文献書誌] steinman,R.M.: "Myeloid dendritic cells." J.Leukocyte Biol.in press. (1998)

[文献書誌] Kohda,K.: "characterization of the mouse PA28 activator complex gene family:Complete organizations of the three member genes and a physical map of the 〜150-kb region containing the α- and β-subunit genes." J.Immunol.160. 4923-4935 (1998)

[文献書誌] Tanaka,K.: "The MHC class I ligand generating system:Roles of immunoproteasomes and the interferon-g-inducible proteasome activator PA28." Immunol.Rev.163. 161-176 (1998)

[文献書誌] Suto.Y.: "Gene arrangement of the killer cell inhibitory receptor family on human chromosome 19q13.4 detected by fiber-FISH." Immunogenetics. 48. 235-241 (1998)

[文献書誌] Kasahara.M.: "What do the paralogous regions in the genome tell us about the origin of the adaptive immune system?" Immunol.Rev.166. 159-175 (1998)

[文献書誌] Kasahara,M.: "the chromosomal duplication model of the major histocompatibility compex." Immunol.Rev.(in press). (1998)

[文献書誌] Kasahara,M.: "Genome paralogy:A new perspective on the organization and origin of the major histocompatibility complex." Curr.Top.Microbiol.Immuno;.(in press). (1999)

[文献書誌] Kimura,Y.: "The regulatory role of heat shock protein 70-reactive CD4+T cells during rat listeriosis." Int.Immunol.10. 117-130 (1998)

[文献書誌] Sakai,T.: "Interleukin 15 activity in the intestinal mucosa of inflammatory bowel disease." Gastroenterology. 114. 1237-1243 (1998)

[文献書誌] Takano,M.: "Dibutyryl cyclic adenosine monophosphate protects mice against tumor necrosis factor-a-induced hepatocyte apoptosis accompanied by increased heat shock protein 70 expression." Cell Stress & Chaperones. 3. 109-117 (1998)

[文献書誌] Washizu,J.: "NF-kB binding site is essential for transcriptional activation of IL-15." Immunogenetics. 48. 1-7 (1998)

[文献書誌] Murosaki,S.: "Heat-killed Lactobacillus plantarum L-137 suppresses naturally fed antigen-specific IgE production by stimulation of IL-12 production in mice." J.Allergy Clin.Immunol.102. 57-64 (1998)

[文献書誌] Takano,M.: "A protective role of IL-15-dependent gd T cells in Escherichia coli infection in mice." Infect.Immun.66. 3270-3278 (1998)

[文献書誌] Takano,M.: "Prostaglandin E2 protects against liver injury after Escherichia coli infection but hampers the resolution of the infection in mice." J.Immunol.161. 3019-3025 (1998)

[文献書誌] Hirose,K.: "Interleukin-15 might be responsible early activation of intraepithelial lynphocytes after oral infection with Listeria monocytogenes in rats." Infect.Immun.66. 6577-5683 (1998)

[文献書誌] Yamada,K.: "Characterization of CD4+ CD8aa+ and CD4- CD8aa- intestinal intraepithelial lymphocytes in rats." Int.Immunol.11. 21-28 (1999)

[文献書誌] Nishimura,H.: "MHC class II-dependent NK1.1+gd T cells are induced in mice by Salmonella infection." J.Immunol.(in press). (1999)

[文献書誌] Mayumi,T.: "IL-15 is elevated in the patients of postoperative enterocllitis." Cytokine. (in press). (1999)

[文献書誌] Kimura,K.: "Immunogene therapy for murine fibrosarcoma using IL-15 gene with high translation efficiency." Eur.J.Immunol.(in press). (1999)

[文献書誌] Ishigami,M.: "The roles of intrahepatic Va 14+Nk1.1+T cells for liver injury induced by Salmonella infection." Hepatology. (in press). (1999)

[文献書誌] Ishigami,M.: "The roles of intrahepatic gd-Tcells for liver injury in mouse induced by Salmonella infection." Microbiol.Immunol.(in press). (1999)

[文献書誌] Hasegawa,T.: "Oral administration of hot water extracts of Chlorella vulgaris reduces IgE production against milk casein in mice." Int.J.Immunopharmacol.(in press). (1999)

[文献書誌] Murosaki,S.: "Immunopotentiating activity of nigerooligosaccharides for T helper 1-like immune response in mice." Biosci.Biotechnol.Biochem.(in press). (1999)

[文献書誌] Mitani,A.: "Interleukin-15 might be responsible for early activation of intestinal intraepithelial lymphocytes after oral infection with Listeria monocytogenes in mice." Immunolgy. (in press). (1999)

[文献書誌] Hirose,K.: "IL-15 might be responsibel for early protection by natural killer cells against infection with avirulent strain of Salmonella cholerasuis mice." J.Leuco.Biol.(in press). (1999)

[文献書誌] Shimokata,T.: "Bystander suppression of natirally fed antigen-specific IgE response by systemic asministration of unrelated antigen." J.Immunol.(in press). (1999)

[文献書誌] Sonoda,E.: "Rad51 deficient vertebrate cells accumulate chromosomal breaks prior to cell death." EMBOJ.17. 598-608 (1998)

[文献書誌] Takata,M.: "Homologous recombination and nonhomologous end joining pathways of DNA double-strand break repair have oberlapping roles in the maintenance of chromosomal integrity in vertebrate cells." EMBOJ.17. 5497-5508 (1998)

[文献書誌] Nishimura,H.: "MHC class II-dependent NK1.1= = cells are induced in mice by Salmonella infection." J.Immunol.(in press). (1999)

[文献書誌] Sano,t.: "Spontaneous clusterin of Thy-1 antigens on CD4+CD8+ thymocytes lacking TCR engagement by MHC/peptide complexes." Eur.J.Immunol.(in press). (1999)

[文献書誌] Gyotoku,T.: "An endogeneously processed self peptide and the corresponding exogenous peptide bound to the same MHC class II molecule could be distinct ligands for TCR with different kinetic stability." Eur.J.Immunol.(in press). (1999)

[文献書誌] Fukui,Y.: "Highly restricted T cell repertoire shaped by a sible MHC/peptide ligand in the presence of signal rearranged T cell receptor beta chain." J.Exp.Med.188. 897-907 (1999)

[文献書誌] Gapin,L.: "Quantitative analysis of the T-cell reperotire by a signal peptide/MHC complex." J.Exp.Med.187. 1871-1883 (1999)

[文献書誌] Takahashi,A.: "Development of peptide vaccines inducing production of neurtralizing antibodies against HIV-I viruses in HLA-DQ6 mice." Vaccine. 16. 1537-1543 (1999)

[文献書誌] 西村泰治: "「免疫遺伝学」医科遺伝学" 南山堂(印刷中),

[文献書誌] 西村泰治: "「MHCの構造と機能:抗原のプロセッシングとT細胞への抗原提示の機構」分子予防医学" 医学書院(印刷中),

[文献書誌] 西村泰治: "「抗原ペプチドのアナログを用いたヒトT細胞の抗原認識と活性化機構の解析」第21回阿蘇シンポジウム" 南山堂(印刷中),

[文献書誌] 入江厚: "「T細胞とMHCの相互作用」免疫 しくみと疾患のすべて" 羊土社, 13 (1998)

1998 年度実績報告書

西村泰治熊本大学, 医学研究科教授 (10156119)

[文献書誌] 入江厚: "「T細胞とMHCの相互作用」免疫しくみと疾患のすべて" 羊土社, 13 (1998)