Analysis of adaptive expression of a T cell self-recognizing structure in radiation bone marrow chimeras.

放射骨髓嵌合体中 T 细胞自我识别结构的适应性表达分析。

• 批准号: 61480155
• 负责人: ASANO Yoshihiro
• 金额: $ 4.16万
• 依托单位: University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1986
• 资助国家: 日本
• 起止时间: 1986 至 1988
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-61480155/
• 关键词: Major histocompatibility complex (MHC); I-J; T cell receptor (TcR); Ca^<++>; Influx; 主要組織適合遺伝子複合体(MHC); I-J; T細胞抗原レセプター; サプレッサーT細胞; ヘルパーT細胞; T細胞クロン; MHC拘束; 放射線照射骨髄キメラ; T細胞認識

Monoclonal antibodies (mAb) against I-region-controlled epitopes expressed exclusively on mature functional T cells but not on B cells and macrophages (anti-Iat and anti-I-J) were found to inhibit class II MHC-restricted cell interactions in the immunological circuit. The present study was undertaken to analyze a mechanism of expression of Iat and I-J epitopes on T cells and to study a functional role of these molecules in immune regulation. Four essential findings were obtained: first, Iat/I-J epitopes undergo systematic alterations according to the environmental MHC in radiation bone marrow chimeras. Secondary, the I-J epitope is not an idiotypic determinant of T cell antigen-receptor (TcR) but is on a distinct molecule from TcR. Third, we have been able to identify the I-J molecule of cloned T cells by the specific immunoprecipitation. The I-J molecule detected is a 90K dimeric molecule composed of 45K glycopeptide subunits distinct from TcR or CD28. Finally, the cross-linking of I-J molecules with specific mAb resulted in the inhibition of Ca_<++> influx induced via the specific stimulation by antigen and MHC. These results indicated that I-J (probably Iat as well) is a T cell surface molecule that transduces a signal to regulate the hydrolysis of intracellular messengers of T cell activation induced via the TcR/T3 complex.

在免疫回路中，抗I区控制表位的单抗(抗Iat和抗I-J)仅在成熟功能T细胞上表达，而不在B细胞和巨噬细胞上表达。本研究旨在分析Iat和I-J表位在T细胞上的表达机制，并研究这些分子在免疫调节中的功能作用。主要研究结果如下：第一，在辐射骨髓嵌合体中，Iat/I-J表位随着环境MHC的变化而发生系统的改变。其次，I-J表位不是T细胞抗原受体(TCR)的独特型决定簇，而是位于与TCR不同的分子上。第三，我们已经能够通过特异性免疫沉淀鉴定克隆的T细胞的I-J分子。检测到的I-J分子是一个90K的二聚体分子，由45K糖肽亚基组成，不同于TCR或CD28。最后，I-J分子与特异性mAb的交联会抑制抗原和MHC诱导的钙内流。这些结果表明，I-J(可能也是Iat)是一种T细胞表面分子，它传递信号来调节TCR/T3复合体诱导的T细胞激活的细胞内信使的水解性。

项目成果

Koyasu,Shigeo: J.Biol.Chem.262. 4689-4695 (1987)

Koyasu，Shigeo：J.Biol.Chem.262。

Tada, Tomio: Idiotypes. Academic Press (New York), 249-262 (1986)

多田富雄：独特型。

Tada, Tomio: Progress in Immunology V. Academic Press (New York), 341-347 (1987)

Tada, Tomio：免疫学进展 V. 学术出版社（纽约），341-347 (1987)

浅野喜博: 感染・炎症・免疫. 18. 263-275 (1988)

Yoshihiro Asano：感染、炎症和免疫 18. 263-275 (1988)。

浅野喜博: "現代免疫学" 医学書院, 57-67 (1988)

浅野义弘：《现代免疫学》医学书院，57-67（1988）