The antigen recognition mechanism by dual receptors of cytotoxic T lymphocytes

细胞毒性T淋巴细胞双受体的抗原识别机制

• 批准号: 14570283
• 负责人: TANABE Masao
• 金额: $ 2.24万
• 依托单位: University of the Ryukyus
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14570283/
• 关键词: cytotoxic T lymphocytes; bone marrow cells; X-chromosome linked gene product; dendritic cell; dual-recognition; immunological tolerance; dual抗原認識; 樹状細胞(DC); 自己寛容

We studied the specificity of cytotoxic T lymphocytes(CTLs) which were induced in mixed lymphocyte cultures(MLC) in vitro. We used the unique culture system that bone marrow(BM) cells from responder mice as accessory cells were added to the cultures, which contained both responder lymph node cells and allogeneic stimulator spleen cells. In this report, two different stimulatory dendritic cell(DC) populations were prepared from spleen cells, such as DEC-205+ cell depleted(Mac-1+ cell enriched;MDC) or Mac-1+ cell depleted(DEC-205+ cell enriched;LDC) spleen cells.In allo-MLC, the CTL induced by the stimulation of MDC had the dual specificity for both allo major histocompatibility antigen complex(MHC) and allo X-chromosome linked gene products(XLGP) of stimulator cells. On the other hand, the CTL induced by the stimulation of LDC had the specificity for allo MHC alone.In polyclonal CTL induction by concanayalin A, autologous, not allogeneic, spleen cells were used as stimulator cells. The CTL induced by MDC-stimuli had the dual specificity, such as polyclonal allo-MHC and stimulator-self-XLGP. On the contrary, when LDC-stimuli was used, the CTL having the dual specificity were specifically suppressed.In conclusion, we suggested that not only MHC but also XLGP had the regulatory function of immune response, such as CTL induction in periphery, and among two DC subpopulations MDC could activate the immune response, the other hand, LDC could suppress that.

我们研究了体外混合淋巴细胞培养（MLC）诱导的细胞毒性T淋巴细胞（ctl）的特异性。我们采用独特的培养系统，将应答小鼠骨髓细胞作为辅助细胞加入到含有应答淋巴结细胞和同种异体刺激脾细胞的培养物中。在本报告中，从脾脏细胞制备了两种不同的刺激树突状细胞（DC）群体，如DEC-205+细胞耗尽（Mac-1+细胞富集；MDC）或Mac-1+细胞耗尽（DEC-205+细胞富集；LDC）脾脏细胞。在同种异体mlc中，MDC刺激诱导的CTL对刺激细胞的同种异体主要组织相容性抗原复合体（MHC）和同种异体x染色体连锁基因产物（XLGP）具有双重特异性。另一方面，LDC刺激诱导的CTL对同种异体MHC具有特异性。在康纳达灵A诱导多克隆CTL的实验中，脾细胞被用作刺激细胞，而不是异体细胞。mdc刺激诱导的CTL具有多克隆alloo - mhc和刺激物-自我xlgp双重特异性。相反，当使用ldc刺激时，具有双重特异性的CTL被特异性抑制。综上所述，除了MHC外，XLGP还具有外周细胞CTL诱导等免疫反应的调节功能，在两个DC亚群中，MDC可以激活免疫反应，而LDC则可以抑制免疫反应。