T细胞及其介导的细胞免疫应答 何睿 ruihe@fudan.edu.cn 免疫学系 上海医学院 复旦大学
T细胞及其介导的细胞免疫应答 何睿 ruihe@fudan.edu.cn 免疫学系 上海医学院 复旦大学
APCs deliver three kinds of signals to naiveT cells APC MHC B7.1 cytokines cass‖l B72 IL-6 L-12 TGF TCR IL-4 CD4 T cell Activation Survival Differentiation
工细胞活化信号传导途径 APC 0044 CD4/CD8 CD3 Lipid raft LAT T cell 70 Adapter proteins nitiation of TCR-mediated ⊙ ⊙ sIgnals SLP-76 P PLCy GTP/GDP activation exchange on Has and Rac Biochemical intermediates Increased cytosolic Ca Diacylglycerol( DAG)RasGTP, Rac.G Distal signaling enzymes Calcineurin PKC AP kinases Transcription factors NFAT AP-1 Abbas et al: Cellular and Molecular Immunology, Updated 6th Edition
T细胞活化信号传导途径
cos (Inducible co-stimulator) 口配体为 ICOSL 口表达于活化的T细胞 口调节活化T细胞产生细胞因子,促进T细胞增殖
ICOS (Inducible co-stimulator) ❑ 配体为ICOSL ❑ 表达于活化的T细胞 ❑ 调节活化T细胞产生细胞因子，促进T细胞增殖
CTLA-4 负性调节T细胞应答 日识别APC表达的B7分子,结合B7的亲和力显著高于 CD28 口表达于活化T细胞 口产生抑制性信号,下调或终止T细胞活化 ITIM(免疫受体酪氨酸抑制基序)
CTLA-4 ❑ 识别APC表达的B7分子，结合B7的亲和力显著高于 CD28 ❑ 表达于活化T细胞 ❑ 产生抑制性信号，下调或终止T细胞活化 ITIM（免疫受体酪氨酸抑制基序） 负性调节T细胞应答
CTLA4的免疫抑制作用机制 A Activation Inhibition by CTLA-4: competition for B7 MHC B7 tMe tMMN 竞争性结合B7 Peptide CD28 TCR CTLA-4 T cell Nucleus Activation Inhibition by CTLA-4 signaling block 抑制T细胞活化信号传导 CD28 CTLA-4 T cell Nucleus Abbas et al: Cellular and Molecular Immunology, Updated 6th Edition
CTLA-4的免疫抑制作用机制 竞争性结合B7 抑制T细胞活化信号传导
PD-1(Programmed death-1 口配体为PD-L1和PD2 口表达于活化的T细胞及其他细胞类型 抑制免疫应答,参与外周免疫耐受的形成
PD-1(Programmed death-1) ❑ 配体为PD-L1和PD-L2 ❑ 表达于活化的T细胞及其他细胞类型 ❑ 抑制免疫应答，参与外周免疫耐受的形成
CD40配体(CD40L) 口TNF超家族成员 冂表达于活化T细胞 口配体为APC表达的CD40 口促进APC活化,增强B7分子的表达,从而 间接扩大T细胞的活化
CD40配体 (CD40L) TNF超家族成员 表达于活化 T 细胞 配体为APC表达的CD40 促进APC活化，增强B7分子的表达，从而 间接扩大T细胞的活化
The B7-CD28 families of costimulators and inhibitory receptors Expression DCs DCs macrophages. i macropl macron macrophages. B cells B cells, othe lymphoid and. lymphoid and Name B7-1 B7-2 ICOS-L PD-L1 B7-H3 B7-H4 CD80) cD86) gands on APCs and other cells Receptors on T cells ITIM motit用uuwn 0 ITSM motif I Tyr.X.X-Met Name CD28 CTLA-4 IcOS PD-1 Expression T cells T cells T cells T cells, B cells constitutive inducible inducible Myleoid cells inducible Maior Costimulation Costimulation Negative regulation Negative function of naive T cells: of effector of T cells ulation ces pulsatory. of T cells T cells
The B7-CD28 families of costimulators and inhibitory receptors
抗原活化初始T细胞和效应T细胞 Lymph node Site of infection Dendritic Naive T cell mphocyte B7 CD28 0000 Effector. T cells CD40L Activated B cells CD40 Naive B cell Activation of effector T cells at site of infection Activation of naive T cells in lymph node, eradication of development of effector cells microbe Abbas et al: Cellular and Molecular Immunology, Updated 6th Edition
抗原活化初始T细胞和效应T细胞