1994 Fiscal Year Annual Research Report

免疫制御の分子機構

Research Project

Project/Area Number	05272104
Research Institution	Kyushu University
Principal Investigator	笹月健彦九州大学, 生体防御医学研究所, 教授 (50014121)
Co-Investigator(Kenkyū-buntansha)	吉開泰信名古屋大学, 医学部, 教授 (90158402) 新井賢一東京大学, 医科研, 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)
Keywords	HLA / トランスジェニックマウス / γδ型T細胞 / アポトーシス / プロテオゾーム / プロセッシング / 免疫制御
Research Abstract	種々の抗原に対する固体の免疫応答あるいは非応答がどのように制御されているかをHLAを軸にした免疫制御系の理解をもとに解明することを目的とし多くの研究成果がえられた。以下に主なるものを列挙する。 1)HLA-B51,-B52、-DR4に結合するペプチドのモチーフを明らかにした。 2)SH基を有する薬剤メルカゾール投与により、インシュリンのS-S基が還元されることにより、プロセッシングが修飾され、HLA-DRB1*0406に支配されるHLA-DR4分子の結合モチーフを有するペプチドがインシュリンから切り出され、自己免疫応答が起こることが明らかになった。 3)2系統のHLA-DRαトランスジェニックマウス(Tg)を用いた実験により、CD4+CD8-細胞の正の選択に関与するMHC分子は、TEC上のMHCクラス11分子であることが明らかになった。 4)γδ型T細胞は、TCRを介したシグナルと同時にLFA-1を介したシグナルが入ることでアポトーシスに陥ること、GvHに際し腸病変を支配することを明らかにした。 5)内在性ペプチドプロセッシングに重要な役割を演じるプロテオゾームの新しいサブユニット、MLPX/MLPY、を発見し、cDNAをクローニングした。

Research Products

(20 results)

All Other

All Publications (20 results)

[Publications] Dong RP: "Characterization of T cell epitopes restricted by HLA-DP9 in streptococcal M12 protein." J.Immunol.(in press).
[Publications] Atsuta N.: "Diversity of Vγ gene segments rearranged to Jγ4 gene segment in mice." J.Immunol.(in press).
[Publications] Suzuki T.: "The regulatory role of γδ T cells in uterine interaepithelial lymphocytes in maternal anti-fetal immune response" J.Immunol.(in press).
[Publications] Adachi Y.: "Positive selection of invariant Vα14_+ T cells by non-major histocompatibility complex-encoded class-I molecules expressed on bone marrow-derived cells." Proc.Natl.Acad.Sci.USA. (in press).
[Publications] Masuda ES.: "A functional member of the NFAT family that is redominantly expressed in the Thymus." Mol.Cell.Biol.(in press).
[Publications] Tsuruta L.: "CAMP inhibits expression of the IL-2 gene throught the NF-AT sequence and transfection of NF-AT cDNAs abrogates the sensitivity of PL-4 cells to cAMP." J.Immunol.(in press).
[Publications] Wan XL.: "HLA-A and DRB4 genes in controlling the susceptibility to Hashimoto's Thyroiditis." Hum.Immunol.(in press).
[Publications] Rae SM.Yeung: "Human CD4-major histocompatibility complex class II (DQW6) transgenic mice in an endogenous CD4/CD8-deficient background:Reconstitution of phenotype and human restricted function." J.Exp.Med.180. 1911-1920 (1994)
[Publications] Yamamoto K.: "Functional interaction between human histocompatibility leukocyte antigen(HLA) class II and mouse CD4 molecule in antigen recognition by T cells in HLA-DR and DQ cransgenic mice." J.Exp.Med.180. 165-171 (1994)
[Publications] Ishihara M.: "Molecular genetic studies of HLA class II alleles in sarcoidosios." Tissue Antigens. 43. 238-241 (1994)
[Publications] Ogawa K.: "A novel HLA-DPB1 allele,DPB1*3601(DPB1*KT)." Tissue Antigens. 44. 134-136 (1994)
[Publications] Kaneshige T.: "Serological and nucleotide sequencing analysis of a novel DR52-associated DRB1 allele with the DR'NJ25' specificity,designated DRB1*1307." Hum.Immunol.41. 151-160 (1994)
[Publications] Kinouchi R.: "Peptide motifs of HLA-DR4/DR53(DRB1*04051DRB4*0101) molecules." Immunogenetics. 40. 376-378 (1994)
[Publications] Salter-Cid L.: "Hsp70 genes are linked to the Xenopus major histocompatibility complex." Immunogenetics. 39. 1-7 (1994)
[Publications] Kato S.: "Isolation of the Xenopus complement factor B complementary DNA and linkage of the gene to the frog MHC." J.Immunol.153. 4546-4554 (1994)
[Publications] Akiyama K.: "cDNA cloning and interferon-γdown-regulation of proteasomal subunits X and Y." Science. 265. 1231-1234 (1994)
[Publications] Fujinami K.: "Purfication and characterization of the 26S proteasome from spinach leaves." J.Biol.Chem.269. 25905-25910 (1994)
[Publications] Tamura T.: "Isolation and characterization of α-type HC3 and β-type HC5 subunit genes of human proteasomes." J.Mol.Biol.244. 117-124 (1994)
[Publications] Matsushita S.: "Allele specificity of structural requirement for peptides bound to HLA-DRB1*0405 and DRB1*0406 complexes:Implication for the HLA-associated susceptibility to methimazole-induced insulin autoimmune syndrome." J.Exp.Med.180. 873-883 (1994)
[Publications] Matsushita S.: "Identification of a T cell membrane protein possible involved in IL-4-induced B cell immunoglobulin class switching to IgE." Cell.Immunol.153. 378-391 (1994)

1994 Fiscal Year Annual Research Report

免疫制御の分子機構

Principal Investigator

笹月健彦九州大学, 生体防御医学研究所, 教授 (50014121)

Research Products

[Publications] Dong RP: "Characterization of T cell epitopes restricted by HLA-DP9 in streptococcal M12 protein." J.Immunol.(in press).

[Publications] Atsuta N.: "Diversity of Vγ gene segments rearranged to Jγ4 gene segment in mice." J.Immunol.(in press).

[Publications] Suzuki T.: "The regulatory role of γδ T cells in uterine interaepithelial lymphocytes in maternal anti-fetal immune response" J.Immunol.(in press).

[Publications] Adachi Y.: "Positive selection of invariant Vα14_+ T cells by non-major histocompatibility complex-encoded class-I molecules expressed on bone marrow-derived cells." Proc.Natl.Acad.Sci.USA. (in press).

[Publications] Masuda ES.: "A functional member of the NFAT family that is redominantly expressed in the Thymus." Mol.Cell.Biol.(in press).

[Publications] Tsuruta L.: "CAMP inhibits expression of the IL-2 gene throught the NF-AT sequence and transfection of NF-AT cDNAs abrogates the sensitivity of PL-4 cells to cAMP." J.Immunol.(in press).

[Publications] Wan XL.: "HLA-A and DRB4 genes in controlling the susceptibility to Hashimoto's Thyroiditis." Hum.Immunol.(in press).

[Publications] Rae SM.Yeung: "Human CD4-major histocompatibility complex class II (DQW6) transgenic mice in an endogenous CD4/CD8-deficient background:Reconstitution of phenotype and human restricted function." J.Exp.Med.180. 1911-1920 (1994)

[Publications] Yamamoto K.: "Functional interaction between human histocompatibility leukocyte antigen(HLA) class II and mouse CD4 molecule in antigen recognition by T cells in HLA-DR and DQ cransgenic mice." J.Exp.Med.180. 165-171 (1994)

[Publications] Ishihara M.: "Molecular genetic studies of HLA class II alleles in sarcoidosios." Tissue Antigens. 43. 238-241 (1994)

[Publications] Ogawa K.: "A novel HLA-DPB1 allele,DPB13601(DPB1KT)." Tissue Antigens. 44. 134-136 (1994)

[Publications] Kaneshige T.: "Serological and nucleotide sequencing analysis of a novel DR52-associated DRB1 allele with the DR'NJ25' specificity,designated DRB1*1307." Hum.Immunol.41. 151-160 (1994)

[Publications] Kinouchi R.: "Peptide motifs of HLA-DR4/DR53(DRB104051DRB40101) molecules." Immunogenetics. 40. 376-378 (1994)

[Publications] Salter-Cid L.: "Hsp70 genes are linked to the Xenopus major histocompatibility complex." Immunogenetics. 39. 1-7 (1994)

[Publications] Kato S.: "Isolation of the Xenopus complement factor B complementary DNA and linkage of the gene to the frog MHC." J.Immunol.153. 4546-4554 (1994)

[Publications] Akiyama K.: "cDNA cloning and interferon-γdown-regulation of proteasomal subunits X and Y." Science. 265. 1231-1234 (1994)

[Publications] Fujinami K.: "Purfication and characterization of the 26S proteasome from spinach leaves." J.Biol.Chem.269. 25905-25910 (1994)

[Publications] Tamura T.: "Isolation and characterization of α-type HC3 and β-type HC5 subunit genes of human proteasomes." J.Mol.Biol.244. 117-124 (1994)

[Publications] Matsushita S.: "Allele specificity of structural requirement for peptides bound to HLA-DRB10405 and DRB10406 complexes:Implication for the HLA-associated susceptibility to methimazole-induced insulin autoimmune syndrome." J.Exp.Med.180. 873-883 (1994)

[Publications] Matsushita S.: "Identification of a T cell membrane protein possible involved in IL-4-induced B cell immunoglobulin class switching to IgE." Cell.Immunol.153. 378-391 (1994)

1994 Fiscal Year Annual Research Report

免疫制御の分子機構

Principal Investigator

笹月 健彦 九州大学, 生体防御医学研究所, 教授 (50014121)

Research Products

[Publications] Dong RP: "Characterization of T cell epitopes restricted by HLA-DP9 in streptococcal M12 protein." J.Immunol.(in press).

[Publications] Atsuta N.: "Diversity of Vγ gene segments rearranged to Jγ4 gene segment in mice." J.Immunol.(in press).

[Publications] Suzuki T.: "The regulatory role of γδ T cells in uterine interaepithelial lymphocytes in maternal anti-fetal immune response" J.Immunol.(in press).

[Publications] Adachi Y.: "Positive selection of invariant Vα14_+ T cells by non-major histocompatibility complex-encoded class-I molecules expressed on bone marrow-derived cells." Proc.Natl.Acad.Sci.USA. (in press).

[Publications] Masuda ES.: "A functional member of the NFAT family that is redominantly expressed in the Thymus." Mol.Cell.Biol.(in press).

[Publications] Tsuruta L.: "CAMP inhibits expression of the IL-2 gene throught the NF-AT sequence and transfection of NF-AT cDNAs abrogates the sensitivity of PL-4 cells to cAMP." J.Immunol.(in press).

[Publications] Wan XL.: "HLA-A and DRB4 genes in controlling the susceptibility to Hashimoto's Thyroiditis." Hum.Immunol.(in press).

[Publications] Rae SM.Yeung: "Human CD4-major histocompatibility complex class II (DQW6) transgenic mice in an endogenous CD4/CD8-deficient background:Reconstitution of phenotype and human restricted function." J.Exp.Med.180. 1911-1920 (1994)

[Publications] Yamamoto K.: "Functional interaction between human histocompatibility leukocyte antigen(HLA) class II and mouse CD4 molecule in antigen recognition by T cells in HLA-DR and DQ cransgenic mice." J.Exp.Med.180. 165-171 (1994)

[Publications] Ishihara M.: "Molecular genetic studies of HLA class II alleles in sarcoidosios." Tissue Antigens. 43. 238-241 (1994)

[Publications] Ogawa K.: "A novel HLA-DPB1 allele,DPB1*3601(DPB1*KT)." Tissue Antigens. 44. 134-136 (1994)

[Publications] Kaneshige T.: "Serological and nucleotide sequencing analysis of a novel DR52-associated DRB1 allele with the DR'NJ25' specificity,designated DRB1*1307." Hum.Immunol.41. 151-160 (1994)

[Publications] Kinouchi R.: "Peptide motifs of HLA-DR4/DR53(DRB1*04051DRB4*0101) molecules." Immunogenetics. 40. 376-378 (1994)

[Publications] Salter-Cid L.: "Hsp70 genes are linked to the Xenopus major histocompatibility complex." Immunogenetics. 39. 1-7 (1994)

[Publications] Kato S.: "Isolation of the Xenopus complement factor B complementary DNA and linkage of the gene to the frog MHC." J.Immunol.153. 4546-4554 (1994)

[Publications] Akiyama K.: "cDNA cloning and interferon-γdown-regulation of proteasomal subunits X and Y." Science. 265. 1231-1234 (1994)

[Publications] Fujinami K.: "Purfication and characterization of the 26S proteasome from spinach leaves." J.Biol.Chem.269. 25905-25910 (1994)

[Publications] Tamura T.: "Isolation and characterization of α-type HC3 and β-type HC5 subunit genes of human proteasomes." J.Mol.Biol.244. 117-124 (1994)

[Publications] Matsushita S.: "Allele specificity of structural requirement for peptides bound to HLA-DRB1*0405 and DRB1*0406 complexes:Implication for the HLA-associated susceptibility to methimazole-induced insulin autoimmune syndrome." J.Exp.Med.180. 873-883 (1994)

[Publications] Matsushita S.: "Identification of a T cell membrane protein possible involved in IL-4-induced B cell immunoglobulin class switching to IgE." Cell.Immunol.153. 378-391 (1994)

笹月健彦九州大学, 生体防御医学研究所, 教授 (50014121)

[Publications] Ogawa K.: "A novel HLA-DPB1 allele,DPB13601(DPB1KT)." Tissue Antigens. 44. 134-136 (1994)

[Publications] Kinouchi R.: "Peptide motifs of HLA-DR4/DR53(DRB104051DRB40101) molecules." Immunogenetics. 40. 376-378 (1994)

[Publications] Matsushita S.: "Allele specificity of structural requirement for peptides bound to HLA-DRB10405 and DRB10406 complexes:Implication for the HLA-associated susceptibility to methimazole-induced insulin autoimmune syndrome." J.Exp.Med.180. 873-883 (1994)