1998 Fiscal Year Annual Research Report

自己免疫疾患と関連した自己抗原ペプチド・HLAクラスII分子複合体の解析

Research Project

Project/Area Number	09470097
Research Institution	Kumamoto University
Principal Investigator	西村泰治熊本大学, 医学研究科, 教授 (10156119)
Co-Investigator(Kenkyū-buntansha)	千住覚熊本大学, 医学研究科, 助手 (50274709) 松下祥熊本大学, 医学研究科, 助教授 (50167649)
Keywords	自己免疫疾患 / 多発性硬化症 / 抗リン脂質抗体症候群 / 全身性エリテマトーデス / 自己抗原 / 自己反応性T細胞 / HLAクラスII分子
Research Abstract	自己免疫疾患の中には、疾患感受性が特定のHLAクラスII対立遺伝子と相関するものがある。本研究は、このような自己免疫疾患の患者において、病因と関連する自己反応性T細胞が認識するHLAクラスII・ペプチド複合体を同定することにより、HLAによる疾患感受性の決定機序を解明することを目的とする。日本人の多発性硬化症(MS)患者を病巣が視神経と脊髄に限られるアジア型MSと、中枢神経系にもある西洋型MSとに大別した場合、西洋型MSは、白人同様にHLA-DRB1^+1501と相関を示すが、アジア型MSはアジア人に特有のDP5(DPA1^0202-DPBP1^0501)と相関することを明らかにした。さらにアジア型MS患者の末梢血中に、3種類のミエリン蛋白(MBP,PLP,MOG)由来のペプチドに反応するT細胞の存在を確認し、これらのT細胞が識別する拘束HLAクラスII分子を同定中である。抗リン脂質抗体症候群(APS)では、リン脂質と結合して構造を変化させたβ2-GPIに対する自己抗体の産生が病因として重視されている。我々は抗β2-GPI抗体陽性のSLE患者群ではHLA-DR9陽性者の頻度が抗体陰性患者群に比べて有意に増加していることを明らかにした。そこで抗β2-GPI抗体陽性のAPSまたはSLE患者からβ2-GPIペプチド反応性CD4^+T細胞株を樹立したところ、18名中の4名の患者からβ2-GPIp154-174あるいはp244-264ペプチド反応性Tho細胞株が得られた。拘束分子はHLA-DRあるいはDPであったが、DR9のものはなかった。以上より、現時点では自己免疫疾患と相関を示すHLAクラスII分子が自己抗原ペプチドを自己反応性T細胞に提示しやすいという仮説を支持する観察は得られておらず、今後さらに症例を増やして検討する予定である。

Research Products

(20 results)

All Other

All Publications (20 results)

[Publications] Chen,Y-Z.: "Modulation of calcium response by altered peptide ligands in a human T cell clone." Eur.J.Immunol.28. 3929-3939 (1998)
[Publications] 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)
[Publications] Yasukawa,M.: "CD4^+ cytotoxic T-cell clones specific for bcr-ab1 b3a2 fusion peptide augment colony formation by chronic myelogenous leukemia cells in a b3a2-specific and HLA-DR-restricted manner." Blood. 92. 3355-3361 (1998)
[Publications] Ito,H.: "HLA-DP -associated susceptibility to optico-spinal from of multiple sclerosis in the Japanese" Tissue Antigens. 52. 179-182 (1998)
[Publications] 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)
[Publications] Oiso,M.: "Differential binding of peptides subtituted at a putative C-terminal anchor residue to I-A^<g7b56His57Ser> and I-A^<g7b56Pro57Asp>." Immunogenetics. 47. 411-414 (1998)
[Publications] Fujii,S.: "The CLIP-substituted invariant chain efficiently targets an antigenic peptide to HLA classII pathway in L cell." Human Immunol.59. 607-614 (1998)
[Publications] Tabata,H.: "Characterization of self-glutamic acid decaboxylase 65-reactive CD4^+ T cell clones established from Japanese patients with insulin dependent diabetes mellitus." Human Immunol.59. 549-560 (1998)
[Publications] Tanaka,Y.: "Efficient induction of human 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)
[Publications] Ohyama,H.: "Human T cell responses to 53-kDa outer membrane protein of Porphyromonas gingivalis in early-onset periodontitis patients." Human Immunol.59. 635-643 (1998)
[Publications] Zeki,K.: "Induction of expression of MHC-class-II antigen on human thyroid carcinoma by wild-type p53." Int.J.Cancer. 75. 391-395 (1998)
[Publications] Hashimiti,H.: "HLA-DRB1 alleles and b2 glycoprotein I-dependent anticardiolipin antibodies in Japanese patients with systemic lupus erythematosus." Clin.Exp.Rheumatol.16. 423-427 (1998)
[Publications] Sadanaga,Y.: "HLA class II association with Type I allergy to house dust mite and Japanese cedar pollen in Japanese subjects." Allergology International. 47. 285-291 (1998)
[Publications] Nishimura,Y.: "(Review)Peptide-based molecular analyses of HLA class II -associated susceptibility to autoimmune diseases." Int.Rev.Immunol.(in press). (1999)
[Publications] 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)
[Publications] Nishimura,Y.: "(Review)Molecular analyses of HLA class II -associated susceptibility to subtypes of autoimmune diseases unique to Asians" Internal.J.Cardiol.66(1). S93-S104 (1998)
[Publications] 西村泰治: "「免疫遺伝学」医科遺伝学" 南山堂(印刷中),
[Publications] 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),
[Publications] 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),
[Publications] 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 Fiscal Year Annual Research Report

自己免疫疾患と関連した自己抗原ペプチド・HLAクラスII分子複合体の解析

Principal Investigator

西村 泰治 熊本大学, 医学研究科, 教授 (10156119)

Research Products

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

[Publications] 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)

[Publications] Yasukawa,M.: "CD4^+ cytotoxic T-cell clones specific for bcr-ab1 b3a2 fusion peptide augment colony formation by chronic myelogenous leukemia cells in a b3a2-specific and HLA-DR-restricted manner." Blood. 92. 3355-3361 (1998)

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

[Publications] 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)

[Publications] Oiso,M.: "Differential binding of peptides subtituted at a putative C-terminal anchor residue to I-A^<g7b56His57Ser> and I-A^<g7b56Pro57Asp>." Immunogenetics. 47. 411-414 (1998)

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

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

[Publications] Tanaka,Y.: "Efficient induction of human 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)

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

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

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

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

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

[Publications] 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)

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

[Publications] 西村泰治: "「免疫遺伝学」医科遺伝学" 南山堂(印刷中),

[Publications] 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),

[Publications] 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),

[Publications] 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)

西村泰治熊本大学, 医学研究科, 教授 (10156119)

[Publications] 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)