Study on self recognition system of T lymphocytes and structural analysis of TCR : CD3 Complex

T淋巴细胞自我识别系统研究及TCR：CD3复合物结构分析

• 批准号: 63480163
• 负责人: ONOE Kazunori
• 金额: $ 4.1万
• 依托单位: Hokkaido University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1988
• 资助国家: 日本
• 起止时间: 1988 至 1989
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-63480163/
• 关键词: Bone marrow chimera; Thymocytes differentiation; Self recognition; Positive selection; Induction of self-tolerance; TCR; Negative selection; T細胞抗原レセプター

1) We found that development of signal transduction system of T cells as well as selection of T cell repertoire were controlled by thymic stroma.2) We analyzed differentiation process of thymocytes from allogeneic bone marrow chimera mice and found that the process was much more complex that had been thought.3) We identified strcmal cells that were essential in inducing self-tolerance. The most important cells were Ia^+ macrophages or dendritic cells in the thymic medulla.4) We found that acute GVHR occurred in the thymus. The GVHR eventually abrogated the induction system of self tolerance in the thymus.5) We identified precise location on H-2 class I molecules that was involved in positive selection of T cell repertoire.6) We identified precise location on H-2 class II molecules that was involved in self class II-restricted recognition of synthetic peptide antigens. The location was well-preserved among different H-2 class II molecules.

1)我们发现T细胞信号转导系统的发育和T细胞库的选择受胸腺基质的控制。2)我们分析了同种异体骨髓嵌合体小鼠胸腺细胞的分化过程，发现这个过程比我们想象的要复杂得多。3)我们发现了在诱导自我耐受中必不可少的基质细胞。胸腺髓质中最重要的细胞是Ia +巨噬细胞或树突状细胞。4)我们发现急性GVHR发生在胸腺。GVHR最终废除了胸腺的自我耐受诱导系统。5)我们确定了参与T细胞库阳性选择的H-2类I分子的精确位置。6)我们在H-2类分子上找到了参与合成肽抗原自我II类限制性识别的精确位置。在不同的H-2 II类分子中，位置保存得很好。

项目成果

Onoe,Kazunori: "Donor and recipient specific tolerance in cells from semi-allogeneic,H-2 subregion compatible or fully allogeneic bone marrow chimeras attributable to clonal deletion" Immunobiol.179. 172-189 (1989)

Onoe，Kazunori：“来自半同种异体、H-2 亚区相容或完全同种异体骨髓嵌合体的细胞中供体和受体特异性耐受可归因于克隆缺失”Immunobiol.179。

Kato,Kazuyuki: "Proceedings of International Symposium on Basic Mechanisms of Granulomatous Inflammation" Elsevier Science Publishers(in press),

加藤和之：“肉芽肿性炎症基本机制国际研讨会论文集”Elsevier Science Publishers（出版中），

Onoe,Kazunori: Acta Pathol.Jpn.38. 101-110 (1989)

Onoe，Kazunori：Acta Pathol.Jpn.38。

Fujita,Masaki: "A study on type II collagen induced arthritis in allogeneic bone marrow chimaera" Immunology. 66. 422-427 (1989)

Fujita，Masaki：“同种异体骨髓嵌合体中 II 型胶原诱导的关节炎的研究”免疫学。

小野江和則: "骨髄移植と網内系-骨髄キメラにおける寛容獲得と維持" 日本網内系誌. 29. 47-56 (1989)

Kazunori Onoe：“骨髓移植和网状内皮系统 - 骨髓嵌合体耐受性的获得和维持”日本网状内皮系统杂志 29. 47-56 (1989)。