T细胞活化的分子机制 2014硕士

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1、T细胞活化机制何睿ruihe@fudan.edu.cn免疫学系上海医学院复旦大学BasedonthehistoryofantigenencounterandthestageofTcellactivation.NaïveTcellsMatureTcellsthathavenotpreviouslyencounteredantigen;Preferentialmigrationtosecondarylymphoidorgans(lymphnodes),wheretheyrecognizeantigenEffectorTcellsActiva

2、tedTcellscapableofperformingthefunctionsrequiredtoeliminateforeignantigensPreferentialmigrationtositesofinfectionorinflammationShort-livedMemoryTcellsLong-lived,functionallysilentcells;MountrapidsecondaryimmuneresponsestothesameantigenexposureHeterogenous(centralandeffe

3、ctor)外周淋巴器官内抗原识别应答诱导T细胞扩增和分化分化的细胞进入循环效应T细胞和其他白细在外周效应T细胞胞迁移到感染部位遭遇抗原效应T细胞活化T细胞的效应功能ActivationofTcellschangestheexpressionofseveralcell-surfacemolecules.FunctionalresponsesofTcellsSecretionofcytokinesProliferationDifferentiationintoeffectorTcellsDifferentiationintomemoryTce

4、llsSecretionofcytokinesOneoftheearliestdetectableresponsesofTcellstoantigenrecognitionPrinciplecytokine:IL-2DistinctsetsofcytokinessecretedbyeffectorTcellsClonalexpansionofTcellsAntigen-presentingcellsarerequiredforTcellactivationTheinitiationofTcellresponsestospecificanti

5、genrequiresSpecificantigenrecognitionbytheTcells;StableadhesionoftheTcellstotheAPCs;TransductionofactivatingsignalstotheTcells.EachoftheseeventsismediatedbydistinctsetsofmoleculesontheTcells.TcellreceptorsandaccessorymoleculesTcellreceptor(TCR)ThedefinitiveTcelllineagemark

6、erRecognitionofMHC-associatedpeptideantigenDualspecificity•MHCrestriction•AntigenspecificityNosignal-transducingfunctionsTCRcomplexComposedofTCRandCD3proteinCD3invariantprotein,identicalinallTcellsregardlessofspecificityresponsibleforsignaling,butnotantigenrecognitionImmu

7、noreceptortyrosine-basedactivationmotif（ITAM)•Containstwocopiesofaconservedsequence:tyrosine-X-X-leucine/isoleucine•ImportantforsignaltransductioninTcellsAntigenrecognitionandsignalingfunctionsofTcells•Antigenrecognition•SignalingfunctionsCo-receptorsAcategoryofmembraneprotei

8、nsthatenhanceTCRsignalingthroughsimultaneousbindingoftheMHCmolecules