Analysis of T cell activation by bacterial extoxins bearing MHC class II-binding activity

具有 MHC II 类结合活性的细菌外毒素对 T 细胞的激活分析

• 批准号: 02807047
• 负责人: UCHIYAMA Takehiko
• 金额: $ 1.02万
• 依托单位: Tokyo Women's Medical College
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1990
• 资助国家: 日本
• 起止时间: 1990 至 1991
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-02807047/
• 关键词: HUVEC; IFN-r; HLA class II; bacterial exotoxins; TSST-1; SEs; HUVEC; ILー2; ブドウ球菌外毒素; MHCクラスII抗原; T細胞受容体(Vβ); 外毒素反応性Tハイブリド-マ; T細胞活性化

Human umbilical vascular endothelial cells (HUVEC) stimulated with recombinant human IFN-r were inveatigated for expression of HLA class II molecules, toxic shock syndrome toxin-1 (TSST-1) and staphylococcal enterotoxin A(SEA)-binding activity and accessory cell (AC) activity in T cell activation by TSST-1, SEA and related exotoxins. HUVEC stimulated with recombinant human IFN-r ranging from 10 to 3000 U/ml for 72 h express HLA class II molecules. Intensity of the expression was dependent on the concentration of IFN-r. HUVEC stimulated with 1000 U/ml of IFN-r for 72 h exhibited ^<125>I-TSST-1 and SEA-binding that was blocked by the unlabeled coresponding toxins and mAb to DR/DP. The activity was not blocked by paraformaldehyde fixation. The IFN-r-stimulated HUVEC exhibited AC activity in IL-2 production in human peripheral T cells stimulated with the several bacterial exotoxins. The activity was blocked by mAb to DR/DP. In view of the facts that TSST-1 and SEs bind directly to HLA class II molecules and activate human T cells in association with HLA class II molecules on AC, it is likely that the acquisition of the above activities in the toxin-induced T cell activation is mediated by the expression of HLA class II molecules. It seems likely that vascular endothelial cells play an important role in the development of pathological changes in patients suffering an acute and systemic illness TSS.

研究用重组人 IFN-r 刺激的人脐血管内皮细胞 (HUVEC) 的 HLA II 类分子、中毒性休克综合征毒素 1 (TSST-1) 和葡萄球菌肠毒素 A (SEA) 的表达以及 TSST-1、SEA 和相关外毒素激活 T 细胞中的辅助细胞 (AC) 活性。用 10 至 3000 U/ml 的重组人 IFN-r 刺激 HUVEC 72 小时，表达 HLA II 类分子。表达的强度取决于IFN-r的浓度。用1000U/ml IFN-r刺激72小时的HUVEC表现出125 I-TSST-1和SEA结合，其被未标记的相应毒素和针对DR/DP的mAb阻断。多聚甲醛固定不会阻断该活性。在用几种细菌外毒素刺激的人外周T细胞中，IFN-r刺激的HUVEC在产生IL-2方面表现出AC活性。该活性被 DR/DP mAb 阻断。鉴于TSST-1和SE直接与HLA II类分子结合并与AC上的HLA II类分子联合激活人T细胞，毒素诱导的T细胞激活中上述活性的获得很可能是由HLA II类分子的表达介导的。血管内皮细胞似乎在患有急性全身性疾病 TSS 的患者的病理变化的发展中发挥着重要作用。

项目成果

内山 竹彦,今西 健一: "ス-パ-抗原特性を示すA群レンサ球菌発熱性外毒素群によるT細胞活性化と異常反応誘導の機序" Medical Immunology. 21. 461-473 (1991)

Takehiko Uchiyama、Kenichi Imanishi：“表现出超抗原特征的 A 组链球菌热原性外毒素诱导 T 细胞激活和异常反应的机制”医学免疫学 21. 461-473 (1991)。

Uchiyama,T.,Imanishi,K.,Araake,M.,Yan,XーJ.,Saito,S.,and Igarashi,H.: "Characterization of toxic shock syndrome toxinー1 binding structures expressed on human peripheral blood mononuclear cells.HLA class II molecules expressed on accessory cells bind the to

Uchiyama, T.、Imanishi, K.、Araake, M.、Yan, X-J.、Saito, S. 和 Igarashi, H.：“人外周血单核细胞上表达的中毒性休克综合征毒素 1 结合结构的表征。辅助细胞上表达的 HLA II 类分子与

Takehiko Uchiyama,Minako Araake,Xiao-Jie Yan,Yukimi Miyanaga,& Hideo Igarashi: "Involvement of HLA clers II molecules in acquisition of staphylococcal enterotoxin A-binding activity and accessory cell activity in activation of human T cell by relatel toxi

内山武彦、荒明美奈子、严晓杰、宫永幸美、

Takehiko Uchiyama, Xiao-Jie Yan, Kenichi Imanishi, Akira Kawachi, Minako Araake, Ryuichi Tachihara, Kunihiro Shinagawa, and Osami Kanagawa.: "Activation of murine T cells by staphylococcal enterotoxin E : Requirement of MHC class II molecules expressed on

Takehiko Uchiyama、Xiao-Jie Yan、Kenichi Imanishi、Akira Kawachi、Minako Araake、Ryuichi Tachihara、Kunihiro Shinagawa 和 Osami Kanakawa。：“葡萄球菌肠毒素 E 激活小鼠 T 细胞：对 MHC II 类分子表达的要求

Takehiko Uchiyama,Minako Araake,XiaoーJie Yan,Yukimi Miyanaga,& Hideo Igarashi: "Involvement of HLA class II molecules in acquisition of staphylococcal enterotoxin Aーbinding activity and accessory cell activity in activation of human T cells by related tox

Takehiko Uchiyama、Minako Araake、Xiao-Jie Yan、Yukimi Miyanaga 和 Hideo Igarashi：“HLA II 类分子参与获得葡萄球菌肠毒素 A 结合活性和相关毒素激活人类 T 细胞的辅助细胞活性