1998 Fiscal Year Annual Research Report

免疫寛容及び免疫非応答の分子機構

Research Project

Project/Area Number	08044302
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)	福井宣規九州大学, 生体防御医学研究所, 助教授 (60243961) MOMBURG Fran ドイツ癌研究所, 助手 VOGT Anne B. ドイツ癌研究所, 助手 KROPSHOFER H ドイツ癌研究所, 助手 HAMMERING Gu ドイツ癌研究所, 教授
Keywords	免疫寛容 / 単-MHC / ペプチド複合体 / トランスジェニックマウス / ノックアウトマウス / T細胞レパートリーの選択 / 安定性
Research Abstract	免疫系はその成熟過程で、自己反応性T細胞の除去および不活化を通して免疫寛容を誘導する。本研究は、MHC分子、抗原ペプチド、T細胞受容体の相互作用を分子レベルで解析することで、胸腺における免疫寛容獲得及び末梢における非応答の分子機構を解明することを目的とし、本年度は以下の知見を得た。 1. 新生児期の組織は、成体の組織と異なり、ナイーブT細胞を感作して、免疫寛容を誘導できることをMHCクラスIトランスジェニックマウスの皮膚移植を用いた系で証明した。 2. 単一MHC/ペプチド複合体を発現したトランスジェニック-ノックアウトマウスにおいて末梢神経系特異的に、CD4陽性TCRαβ陽性T細胞およびマクロファージの浸潤を主体とする自己免疫疾患が発症することを見いだし、その発症に胸腺でのT細胞レパートリーの選択が関与していることを示した。 3. 同一のMHCクラスIIと自己抗原ペプチドの組み合わせより安定性の異なる2種類の複合体が形成され、それぞれが相異なるTCRリガンドとなることを明らかにした。また、免疫寛容は安定な複合体に対してのみ誘導される可能性を示唆した。

Research Products

(12 results)

All Other

All Publications (12 results)

[Publications] Nishimura H.: "MHC class II-dependent Mk1.1 T.cells are induced in mice by Salmcnella infection." J.Immunol.(in press). (1999)
[Publications] Savoie CJ.: "The peptide binding moif of HLA-A0217." Immunogenetics. (in press). (1999)
[Publications] Alferink J.: "Control of neonatal tolerance to tissue anigens by peripheral T cell trafficking" Science. 282. 1338-1341 (1998)
[Publications] Kropshofer H.: "A role for KLA-DO as a co-chaperone of HLA-DM in peptide loading of MHC class II molecules." EMBO J.17. 2971-2981 (1998)
[Publications] Gyotoku T.: "An endogenously procesed self peptide and the corresponding exogenous peptide bound to the same MHC class II molecule could be distiact ligands for TCR with different-kinetic stability." Eur.J.Immunol.28. 4050-4061 (1998)
[Publications] Ono T.: "Molecular analysis of HLA class I(HLA-A and -B)and HLA HLA class II(HLA-DRB1)genes in Japanese patients with cultiple sclerosis(Westers type and istan type)." Tissue Antigens. 52. 539-542 (1998)
[Publications] Sasazuki T.: "Effect og matching of class I HLA alleles on clinicalout come after transplantation of hemaopoieic stem cells cells from an urrelated dohor." New Engl.J.Med.339. 1177-1185 (1998)
[Publications] Takahashi A.: "Development of peptide vaccines inducing production of neutralizing antibodeies against HIV-1 viruses in HLA-DQ6" Vaccine. 16. 1537-1543 (1998)
[Publications] Fukui Y.: "Highly restricted T cell repertoire shaped by a single major histocompatibility complex-peptide ligand in the resence of a single rearranged T cell receptos β chain." J.Exp.Med.188. 897-907 (1998)
[Publications] Gapin L.: "Quantitative analysis of the T-cell repertoire by a single peptide/MHC complex." J.Exp.Med.187. 1871-1883 (1998)
[Publications] Savoie CJ.: "MHC class I bound peptides of a colon carcinoma cell line,a Ki-ras gene-targeted progeny cell line and a B cell line." Cancer Letters.123. 193-197 (1998)
[Publications] Tana T.: "A HLA binding motif-aided peptide epitope library:A novel library design for the screening of HLA-DR4-restric antigenic peptiees recognized by CD4 T cells" J.Human Genet.43. 14-21 (1998)

1998 Fiscal Year Annual Research Report

免疫寛容及び免疫非応答の分子機構

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] Nishimura H.: "MHC class II-dependent Mk1.1 T.cells are induced in mice by Salmcnella infection." J.Immunol.(in press). (1999)

[Publications] Savoie CJ.: "The peptide binding moif of HLA-A0217." Immunogenetics. (in press). (1999)

[Publications] Alferink J.: "Control of neonatal tolerance to tissue anigens by peripheral T cell trafficking" Science. 282. 1338-1341 (1998)

[Publications] Kropshofer H.: "A role for KLA-DO as a co-chaperone of HLA-DM in peptide loading of MHC class II molecules." EMBO J.17. 2971-2981 (1998)

[Publications] Gyotoku T.: "An endogenously procesed self peptide and the corresponding exogenous peptide bound to the same MHC class II molecule could be distiact ligands for TCR with different-kinetic stability." Eur.J.Immunol.28. 4050-4061 (1998)

[Publications] Ono T.: "Molecular analysis of HLA class I(HLA-A and -B)and HLA HLA class II(HLA-DRB1)genes in Japanese patients with cultiple sclerosis(Westers type and istan type)." Tissue Antigens. 52. 539-542 (1998)

[Publications] Sasazuki T.: "Effect og matching of class I HLA alleles on clinicalout come after transplantation of hemaopoieic stem cells cells from an urrelated dohor." New Engl.J.Med.339. 1177-1185 (1998)

[Publications] Takahashi A.: "Development of peptide vaccines inducing production of neutralizing antibodeies against HIV-1 viruses in HLA-DQ6" Vaccine. 16. 1537-1543 (1998)

[Publications] Fukui Y.: "Highly restricted T cell repertoire shaped by a single major histocompatibility complex-peptide ligand in the resence of a single rearranged T cell receptos β chain." J.Exp.Med.188. 897-907 (1998)

[Publications] Gapin L.: "Quantitative analysis of the T-cell repertoire by a single peptide/MHC complex." J.Exp.Med.187. 1871-1883 (1998)

[Publications] Savoie CJ.: "MHC class I bound peptides of a colon carcinoma cell line,a Ki-ras gene-targeted progeny cell line and a B cell line." Cancer Letters.123. 193-197 (1998)

[Publications] Tana T.: "A HLA binding motif-aided peptide epitope library:A novel library design for the screening of HLA-DR4-restric antigenic peptiees recognized by CD4 T cells" J.Human Genet.43. 14-21 (1998)

笹月健彦九州大学, 生体防御医学研究所, 教授 (50014121)