1995 年度実績報告書

免疫制御の分子機構

研究課題

研究課題/領域番号	05272104
研究機関	九州大学
研究代表者	笹月健彦九州大学, 生体防御医学研究所, 教授 (50014121)
研究分担者	吉開泰信名古屋大学, 医学部, 教授 (90158402) 新井賢一東京大学, 医科学研究所, 教授 (00012782) 谷口克千葉大学, 医学部, 教授 (80110310) 猪子英俊東海大学, 医学部, 教授 (10101932) 片桐一旭川医科大学, 医学部, 教授 (10041823)
キーワード	HLA / 抗原ペプチド / TCR / プロセッシング / プロテアゾーム
研究概要	種々の抗原に対する個体の免疫応答あるいは非応答がどの様に制御されているかを、HLA/抗原ペプチド複合体のTCRによる認識とそれによりもたらされるサイトカインの発現を中心に免疫制御系を分子レベルで解明することを目的とし、以下に示す多くの研究成果が得られた。 1.免疫応答とHLAとの相関をDNAのレベルで詳細に解析することにより、多重遺伝子族であるHLAクラスI、クラスII分子による免疫制御機構を明らかにした。 2.アレルギー疾患の原因となる抗原のHLA結合ペプチドを同定し、また発症に重要な意味をもつIgE生産がカテプシンBの阻害により抑制されることを明らかにした。 3.自己免疫疾患感受性および非感受性HLA分子より、結合ペプチドを溶出し、そのモチーフの相違を明らかにした。 4.HLA領域にマップされる遺伝子によりコードされる単球系細胞特異的抗原に対する単クローン抗体を樹立した。 5.抗原ペプチドの生成に関与するプロテアソームおよびその関連遺伝子のクローニングに成功した。 6.Vα14TCRがNKT細胞の分化に必須であることを明らかにした。 7.γδ型T細胞の増殖およびGVH反応における新しい知見を得た。 8.サイトカイン遺伝子の発現に関与する転写因子の存在様式がTh1とTh2で異なること、およびIL-1がThoへの分化を制御していることを明らかにした。 9.Ts細胞による抗体産生抑制機構が未知の可溶性因子によることを示した。

研究成果
(20件)

すべてその他

すべて文献書誌 (20件)

[文献書誌] Mineta M.: "Contribution of HLA class I and class II alleles to the regulation of antibody production to hepatitis B surface antigen in humans" Int. Immunol.(in press).
[文献書誌] Hori T.: "Japanese cedar pollinosis and HLA-DP5" Tissue Antigens. (in press).
[文献書誌] Min W.: "Identification of an epitope for T cells correlated with antibody response to hepatitis B surface antigen in vaccinated humans" Hum. Immunol.(in press).
[文献書誌] Nishimura H.: "IL-15 is a novel growth factor for murine T cells induced by Salmonella infection" J. Immunol.(in press).
[文献書誌] Matsushita S.: "HLA-DQ-binding peptide motifs. I. Comparative binding analysis of type II collagen-derived peptides to DR and DQ molecules of rheumatoid arthritis-susceptible and non-susceptible haplotypes" Int. Immunol.(in press).
[文献書誌] DeMartino G. M.: "Identification, purification, and chracterization of a PA700-dependent actvator of the proteasome" J. Biol. Chem.(in press).
[文献書誌] Adachi Y.: "Positive selection of invariant V 14+ T cells by non-major histocompatibility complex-encoded class I-like molecules expressed on bone marrow-derived cells" Proc. Natl. Acad. Sci. USA. 92. 1200-1204 (1995)
[文献書誌] Masuda E. S.: "NFATx: a functional member of the NFAT family that is predominantly expressed in the thymus" Mol. Cell. Biol.15. 2697-2706 (1995)
[文献書誌] Watanabe S.: "Granulocyte-macrophage colony stimulation factor dependent replication of polyoma virus replicon in hematopoietic cells: Analyses of receptor signals for replication and transcription" J. Biol. Chem.270. 9615-9621 (1995)
[文献書誌] Sakai T.: "Host intestinal intraepithelial T lymphocytes present during acute graft-versus-host disease in mice may contribute to the development of enteropathy" Eur. J. Immunol.25. 87-91 (1995)
[文献書誌] Noguchi M.: "The MHC class I-like Zn-2-glycoprotein gene maps to mouse chromosome 5" Immunogenetics. 42. 72-74 (1995)
[文献書誌] Matsuoka S.: "A novel type of cell death of lymphocytes induced by a monoclonal antibody without participation of complement" J. Exp. Med.181. 2007-2015 (1995)
[文献書誌] Hisamatsu H.: "Newly identified pair of proteasomal subunits regulated reciprocally by interferon-" J. Exp. Med.(in press).
[文献書誌] Sudo T.: "Differences in MHC-class I self peptide repertoires among HLA-A2 subtypes" J. Immunol.155. 4749-4756 (1995)
[文献書誌] Futaki G.: "Naturally processed HLA-DR9/DR53(DRB1^*0901/DRB4^*0101)-bound peptides" Immunogenetics. 42. 299-301 (1995)
[文献書誌] Fukagawa T.: "A boundary of long-range G+C% mosaic domains in the human MHC locus: Pseudoautosomal boundary-like sequence exists near the boundary" Genomics. 25. 184-191 (1995)
[文献書誌] Altmann D. M.: "The T cell response of HLA-DR transgenic mice to myelin basic protein and other antigens in the presence and absence of human CD4" J. Exp. Med.181. 867-875 (1995)
[文献書誌] Sumida T.: "Selective reduction of T cells bearing invariant V 24J Q antigen receptor in patients with systemic sclerosis" J. Exp. Med.182. 1163-1168 (1995)
[文献書誌] Suzuki G.: "Impaired CD28-mediated costimulation in anergic T cells" Int. Immunol.7. 37-43 (1995)
[文献書誌] Matsunaga Y.: "Participation of cathepsin B in processing of antigen presentation to MHC class II" FEBS Lett.324. 325-330 (1993)

1995 年度 実績報告書

免疫制御の分子機構

研究代表者

笹月 健彦 九州大学, 生体防御医学研究所, 教授 (50014121)

研究成果

[文献書誌] Mineta M.: "Contribution of HLA class I and class II alleles to the regulation of antibody production to hepatitis B surface antigen in humans" Int. Immunol.(in press).

[文献書誌] Hori T.: "Japanese cedar pollinosis and HLA-DP5" Tissue Antigens. (in press).

[文献書誌] Min W.: "Identification of an epitope for T cells correlated with antibody response to hepatitis B surface antigen in vaccinated humans" Hum. Immunol.(in press).

[文献書誌] Nishimura H.: "IL-15 is a novel growth factor for murine T cells induced by Salmonella infection" J. Immunol.(in press).

[文献書誌] Matsushita S.: "HLA-DQ-binding peptide motifs. I. Comparative binding analysis of type II collagen-derived peptides to DR and DQ molecules of rheumatoid arthritis-susceptible and non-susceptible haplotypes" Int. Immunol.(in press).

[文献書誌] DeMartino G. M.: "Identification, purification, and chracterization of a PA700-dependent actvator of the proteasome" J. Biol. Chem.(in press).

[文献書誌] Adachi Y.: "Positive selection of invariant V 14+ T cells by non-major histocompatibility complex-encoded class I-like molecules expressed on bone marrow-derived cells" Proc. Natl. Acad. Sci. USA. 92. 1200-1204 (1995)

[文献書誌] Masuda E. S.: "NFATx: a functional member of the NFAT family that is predominantly expressed in the thymus" Mol. Cell. Biol.15. 2697-2706 (1995)

[文献書誌] Watanabe S.: "Granulocyte-macrophage colony stimulation factor dependent replication of polyoma virus replicon in hematopoietic cells: Analyses of receptor signals for replication and transcription" J. Biol. Chem.270. 9615-9621 (1995)

[文献書誌] Sakai T.: "Host intestinal intraepithelial T lymphocytes present during acute graft-versus-host disease in mice may contribute to the development of enteropathy" Eur. J. Immunol.25. 87-91 (1995)

[文献書誌] Noguchi M.: "The MHC class I-like Zn-2-glycoprotein gene maps to mouse chromosome 5" Immunogenetics. 42. 72-74 (1995)

[文献書誌] Matsuoka S.: "A novel type of cell death of lymphocytes induced by a monoclonal antibody without participation of complement" J. Exp. Med.181. 2007-2015 (1995)

[文献書誌] Hisamatsu H.: "Newly identified pair of proteasomal subunits regulated reciprocally by interferon-" J. Exp. Med.(in press).

[文献書誌] Sudo T.: "Differences in MHC-class I self peptide repertoires among HLA-A2 subtypes" J. Immunol.155. 4749-4756 (1995)

[文献書誌] Futaki G.: "Naturally processed HLA-DR9/DR53(DRB1^*0901/DRB4^*0101)-bound peptides" Immunogenetics. 42. 299-301 (1995)

[文献書誌] Fukagawa T.: "A boundary of long-range G+C% mosaic domains in the human MHC locus: Pseudoautosomal boundary-like sequence exists near the boundary" Genomics. 25. 184-191 (1995)

[文献書誌] Altmann D. M.: "The T cell response of HLA-DR transgenic mice to myelin basic protein and other antigens in the presence and absence of human CD4" J. Exp. Med.181. 867-875 (1995)

[文献書誌] Sumida T.: "Selective reduction of T cells bearing invariant V 24J Q antigen receptor in patients with systemic sclerosis" J. Exp. Med.182. 1163-1168 (1995)

[文献書誌] Suzuki G.: "Impaired CD28-mediated costimulation in anergic T cells" Int. Immunol.7. 37-43 (1995)

[文献書誌] Matsunaga Y.: "Participation of cathepsin B in processing of antigen presentation to MHC class II" FEBS Lett.324. 325-330 (1993)

1995 年度実績報告書

笹月健彦九州大学, 生体防御医学研究所, 教授 (50014121)

[文献書誌] Futaki G.: "Naturally processed HLA-DR9/DR53(DRB1^0901/DRB4^0101)-bound peptides" Immunogenetics. 42. 299-301 (1995)