T-细胞激活演示教学.ppt

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1、T细胞激活TCellActivationT细胞激活和增殖涉及的分子与信号信号转导过程T细胞功能性亚群的分化记忆T细胞超抗原T细胞抗原识别信号的转导pathwayApathwayBpathwayCPKCcalcineurinMAPkinasePIP2DAG+IP3Ras-GDPRas-GTPCa2+RafPLC-SosNF-ATOCTNF-BAP-1NF-ATOCTPKCGrb-2I-BNF-BNF-BNF-ATNF-AT-pc-Junc-FosAKTB7CD28PI3-KLATSLP-76ZAP-70Peptide-MHCTCRLckFynCD45C

2、D4PTPdomainsY505pITAMITAMYpYpNUCLEUSCELLMEMBRANEIL-2geneYpYpYpGSK3GadsNCK细胞骨架重排免疫突触PIPIP3TCRCD3ITAM受体交联成簇偶联PTK活化（Lck、Fyn）ITAM磷酸化（活化）招募胞浆PTK（ZAP-70）PTK磷酸化（活化）激活衔接蛋白PLC-PIP2DAG+IP3GEF（Sos）激活PKC活化钙调磷酸酶活化MAP激酶级联反应活化转录因子（NF-B、NFAT、AP-1）与特异性基因的启动子结合，启动基因转录转位CD3和CD4的胞内段连接有PTKCD3的胞内段具有ITAM结构Srcf

3、amily:Lck,Fyn,Lyn,BlkTyrosinekinaseSykfamily:ZAP-70,SykJakfamily:Jak1,Jak2,Jak3ProteinkinaseCskfamily:CskProteinkinaseC(PKC)Serine/threonineMAPkinase(MAP:mitogen-activationkinaseprotein)PI3kinase(PI:phosphatylinositide)TyrosinephosphataseCD45ProteinphosphataseSerine/threonineCalcineurin钙调磷

4、酸酶phosphataseProteinkinasesandproteinphosphatasesinT/Bactivation蛋白激酶蛋白磷酸酶蛋白酪氨酸激酶PTK蛋白酪氨酸磷酸酶PTP蛋白激酶Ｃ蛋白丝/苏氨酸激酶PITAM基序(免疫受体酪氨酸激活基序)immunoreceptortyrosinebasedactivationmotif以YxxL/V4个氨基酸残基为基本结构的序列存在于CD3、IgIg、FcRIII(CD16)、FcRI等活化性受体的胞内段（T、B、NK、肥大细胞）其酪氨酸被磷酸化后，可招募含有SH2结构域的一些游离胞浆分子，参与信号转导的级联反应

5、为T、B细胞转导抗原刺激信号所必需衔接蛋白：LAT（、SLP-76）招募Grb-2、Gads和PLC-磷脂酰肌醇途径Grb-2招募GEF（Sos）MAP激酶途径Gads招募NCK免疫突触形成鸟苷酸置换因子：guaninenucleotideexchangefactor，GEF小G蛋白：smallGTP-bindingproteinErk-andJnk-pathwaysinMAPkinase-relatedsignalingcascade?PakRafMekkMekLnkkErkJnkFosJunAP-1RasRac,cdc42TactivationBactivation/

6、StressGTPproteinMAPKKKKMAPKKKMAPKKMAPKTranscriptionfactorp38协同刺激信号的转导pathwayApathwayBpathwayCPKCcalcineurinMAPkinasePIP2DAG+IP3Ras-GDPRas-GTPCa2+RafPLC-SosNF-ATOCTNF-BAP-1NF-ATOCTPKCGrb-2I-BNF-BNF-BNF-ATNF-AT-pc-Junc-FosAKTB7CD28PI3-KLATSLP-76ZAP-70Peptide-MHCTCRLckFynCD45CD4PT

7、PdomainsY505pITAMITAMYpYpNUCLEUSCELLMEMBRANEIL-2geneYpYpYpGSK3GadsNCK细胞骨架重排免疫突触PIPIP3细胞因子受体启动的信号转导T细胞功能性亚群的分化CD4Th1CD4Th2CD4Th17CD8CTLTCR配体pMHCII类pMHCII类pMHCII类pMHCI类诱导因子IL-12、IFN-IL-4IL-23IL-2转录因子STAT4STAT6/GATA3STAT3/RORtSTAT1/T-bet表面效应分子CD40L、FasLCD40LFas