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.

本文研究了混合淋巴细胞培养物（MLC）体外诱导的细胞毒性T淋巴细胞（CTL）的特异性。我们使用了独特的培养系统，即将来自应答小鼠的骨髓（BM）细胞作为辅助细胞加入到培养物中，该培养物含有应答淋巴结细胞和同种异体刺激脾细胞。本研究从去DEC-205+细胞的脾细胞中制备了两种不同的刺激性树突状细胞（DC）群，（Mac-1+细胞富集;MDC）或Mac-1+细胞耗竭（DEC-205+细胞富集;在allo-MLC中，MDC诱导的CTL对同种异体主要组织相容性抗原复合物（MHC）和同种异体X染色体连锁基因产物具有双重特异性，XLGP）。在用刀豆素A诱导的多克隆CTL中，用自体脾细胞而不是同种脾细胞作为刺激细胞。MDC刺激物诱导的CTL具有双重特异性，如多克隆的allo-MHC和刺激物自身的XLGP。因此，我们认为，除了MHC外，XLGP也具有诱导外周CTL等免疫应答的调节功能，在两种DC亚群中，MDC可以激活免疫应答，而LDC则可以抑制免疫应答。