7共刺激分子及其调节网络的研究进展和思考张学光ppt.ppt

共刺激分子及其调节网络的研究进展和思考 苏州大学生物技术研究所 张学光 免疫系统的自我感知和反馈调节 SLAM signaling lymphocyte activation molecule 共刺激分子的本质取决于两个因素 同一配体由于与其结合的特异性受体不同，可产生协同刺激或协同抑制作用 1.Signal transduction through ligands reverse signaling through motifs in cytoplasma. Watts confirmed that the PTK（CK I）motif exists in the N-terminal of memberane TNF 、4-1BBL、CD30L、CD40L, which could regulate the influx of calcium, even the downstream molecules remain unknown. 3.Reverse signaling through another receptor 1）CD40L transduces signal by CD28i 2）4-1BBL transduces signal through TLR 3 Transmembrane co-signal complex What is immunological synapse 正性共信号分子CD28/B7-1/2、ICOS/GL50、4-1BB/4-1BBL、OX40/OX40L等和负性共信号分子CTLA-4/B7-1（B7-2）、PD-1/PD-L1（PD-L2）、BTLA/HVEM等的受体/配体在T细胞活化过程中呈现调节性共表达，并形成的脂质为基础的信号分子复合体—免疫突触，使信号有效和有序的整合，对效应T细胞在外周免疫应答中实现自我调节，从而使机体能够有效地启动特异性免疫应答、维持该应答的精确与平衡并适时终止之具有重要的调控作用。 4-1BBL transduces signal through TLR 小 结 共刺激分子构成调节网络，参与免疫应答的启发，抗原信息传递，免疫应答类型及效应； 共刺激分子在免疫细胞表达呈多样化，与其调节功能相关，一系列共刺激分子可以形成免疫突触形式，达到整个信号更加精确调节； 协同信号以膜型分子和可溶性分子两种形式存在，以及通过双向信号传递，构成调节网络，参与免疫应答的启动，抗原信息传递，免疫应答类型及效应，以及适时中止。 Relative cell Number 4-1BB 4-1BBL Pre-DC 3d DC 5d DC AP-DC CD40-24h-DC CD40-48h-DC Pre-DC 3d DC 5d DC AP-DC CD40-24h-DC CD40-48h-DC Log Fluroescence intensity 4-1BB、4-1BBL 41BBL/41BB信号在固有免疫和适应性免疫中的调节作用 Figure Synergy with CD40 in the induction of CD8 T cell proliferation and differentiation is a property of multiple TLR agonists. Combined TLR and CD40 Triggering Induces Potent CD8+ T Cell Expansion with Variable Dependence on Type I IFN J.EXP.MED 2004, 199: 775-784 FIGURE： Ligands for TLR9 and TLR7/8 inhibit B7h down-regulation and shedding on B cells. For flow cytometric histograms, B7h staining with treatment shaded and without treatment heavy dashed line are shown with background staining levels light dashed line . ICOS-Induced B7h Shedding on B Cells Is Inhibited by TLR7/8 and TLR9 The Journal of Immunology, 2006, 177: 2356–2364. TLR4–4-1BBL complex appeared on macrophage between 2 h and 12 h