1997 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, 助手 (60243961) 上川路信博九州大学, 生体防御医学研究所, 助教授 (90224659) VOGT Anne B. ドイツ癌研究所, 助手 KROPSHOFER H ドイツ癌研究所, 助手 HAMMERLING G ドイツ癌研究所, 教授
Keywords	主要組織適合抗原 / T細胞受容体 / 抗原ペプチド / プロセシング / HLA-DM / HLA-DO / 免疫制御 / 胸腺内T細胞の選択
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、その機構を分子レベルで解明することを目的とし、以下の知見を得た。 1.HLA-DM分子がMHCクラスII分子の細胞内輸送過程で、その凝集を阻止するシャペロン機能を有し、またoff-rateの速い抗原ペプチドを選択的にとり除く校正機能を有することを明らかにした。さらに、HLA-DOがDM分子のこれらの作用を増強する知見を得た。 2.単一MHC/ペプチド複合体により選択されたT細胞上のTCRα鎖を、再構成したTCRβ導入遺伝子の存在下で詳細に検討することにより、正の選択においても特異的TCR-ペプチド相互作用が関与しており、ペプチドの構造そのものがT細胞レパートリーに正に選択を介して影響し得ることを明らかした。 3.HLAトランスジェニックマウスを用いて、HLA分子に拘束されたマウスT細胞の機能をin vitro及びin vivoで解析することで、異種間の免疫応答が弱いのはMHCの構造上の違いに起因するのではなく、むしろ他の接着分子等の種差によることが示唆された。

Research Products

(10 results)

All Other

All Publications (10 results)

[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. (in press).
[Publications] Tana T.: "A HLA binding motif-aided peptide epitope library : A novel library design for the screening of HLA-DR4-restricted antigenic peptides recogmized by CD4+ T cells." J.Human Genet.(in press).
[Publications] Vergelli M.: "Modifications of peptide antigens with superagonist activity suggest multiple stimulatory ligands for autoreactiye T cells." J.Immunol.(in press).
[Publications] Fukui Y.: "Differential requirement of MHC class II molecules expressed on haematopoietic cells for positive selection of CD4+ thymocytos in TCRab and TCRb transgcnic mice." Int.Immunol.vol.9. 1385-1391 (1997)
[Publications] Ishimoto T.: "In Vitro and In Vivo evidence for high frequency of I-Ab-reactive CD4+ T cells in HLA-DQ or HLA-DRA transgenic mice lacking endogenous MHC class I and/or class II expression." J.Immunol.vol.159. 3717-3722 (1997)
[Publications] Fukui Y.: "Positive and negative CD4+ thymocyte selection by a single MHC class II/peptide ligand affected by its expression level in the thymus." Immunity. vol.6. 401-410 (1997)
[Publications] Takeshita T.: "Identification of HLA-DO6-derived peptide recognized by mouse MHC class I H-2Db-restricted CD8+ T cells in HLA-DO6 transgcnic mice." Jpn.J.Human Genet.vol.42. 225-232 (1997)
[Publications] Vergelli M.: "HLA-DR restricted presentation of purified myelin basic protein is independent of intracellular processing." Eur.J.Immunol.vol.27. 941-951 (1997)
[Publications] Kropshofer H.: "How HLA-DM edits the MHC II peptide repertoires : Survival of the fittest?" Immunology Today. vol.18. 77-82 (1997)
[Publications] Kropshofer H.: "HLA-DM acts as a molecular chaperone and rescues empty HLA-DR molecules at lysosomal pH." Immunity. vol.6. 293-302 (1997)

1997 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] 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. (in press).

[Publications] Tana T.: "A HLA binding motif-aided peptide epitope library : A novel library design for the screening of HLA-DR4-restricted antigenic peptides recogmized by CD4+ T cells." J.Human Genet.(in press).

[Publications] Vergelli M.: "Modifications of peptide antigens with superagonist activity suggest multiple stimulatory ligands for autoreactiye T cells." J.Immunol.(in press).

[Publications] Fukui Y.: "Differential requirement of MHC class II molecules expressed on haematopoietic cells for positive selection of CD4+ thymocytos in TCRab and TCRb transgcnic mice." Int.Immunol.vol.9. 1385-1391 (1997)

[Publications] Ishimoto T.: "In Vitro and In Vivo evidence for high frequency of I-Ab-reactive CD4+ T cells in HLA-DQ or HLA-DRA transgenic mice lacking endogenous MHC class I and/or class II expression." J.Immunol.vol.159. 3717-3722 (1997)

[Publications] Fukui Y.: "Positive and negative CD4+ thymocyte selection by a single MHC class II/peptide ligand affected by its expression level in the thymus." Immunity. vol.6. 401-410 (1997)

[Publications] Takeshita T.: "Identification of HLA-DO6-derived peptide recognized by mouse MHC class I H-2Db-restricted CD8+ T cells in HLA-DO6 transgcnic mice." Jpn.J.Human Genet.vol.42. 225-232 (1997)

[Publications] Vergelli M.: "HLA-DR restricted presentation of purified myelin basic protein is independent of intracellular processing." Eur.J.Immunol.vol.27. 941-951 (1997)

[Publications] Kropshofer H.: "How HLA-DM edits the MHC II peptide repertoires : Survival of the fittest?" Immunology Today. vol.18. 77-82 (1997)

[Publications] Kropshofer H.: "HLA-DM acts as a molecular chaperone and rescues empty HLA-DR molecules at lysosomal pH." Immunity. vol.6. 293-302 (1997)

笹月健彦九州大学, 生体防御医学研究所, 教授 (50014121)