《细胞进展TCRMH》PPT课件

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1、T细胞识别抗原的分子基础一、TCR及其共受体二、MHC分子及其与抗原肽的相互作用三、MHC多聚体及其应用T细胞对抗原的识别是特异性免疫应答发生的先决条件T细胞识别抗原的物质基础是其表面的TCRTCR识别的配体是与MHC分子结合的抗原肽TCR识别需要CD4/CD8分子作为共受体AntigenrecognitionbyTcellsrequirespeptideantigensandpresentingcellsthatexpressMHCmoleculesMHC分子提呈抗原肽供T细胞识别一、T细胞抗

2、原受体（TCR）结构基因及多样性形成的机制与抗原肽/MHC复合物的相互作用ThestructureoftheTcellreceptorStructureofTCRissimilartothatofFab图1Threesetsofkeyantigen-recognitionreceptorshavesimilaroverallanatomies图2Domainstructure:IggenesuperfamilyMonovalentNoalternativeconstantregionsNeversecre

3、tedHeterodimeric,chainsaredisuphide-bondedVeryshortintracytoplasmictailPositivelychargedaminoacidsintheTMregionAntigencombiningsitemadeofjuxtaposedVaandVbregions30,000identicalspecificityTcRpercellTheTcellantigenreceptor•TcRarehighlyvariableinanindividual•D

4、iversityfocusesonsmallchangesintheshapepresentedattheendoftheTcellreceptor(CDR).•ThemechanismsresponsibleforvariabilityarecloselyrelatedtothedevelopmentalstagesofTcells•Themechanismsofdiversitygenerationaresimilartothoseusedintheimmunoglobulingeneswithrespe

5、ctto:Geneorganisation,rearrangementandrandomjoiningerrorTcellantigenreceptordiversityGenerationofdiversityintheTcRCOMBINATORIALDIVERSITYMultiplegermlinesegmentsInthehumanTcRVariable(V)segments:~70,52Diversity(D)segments:0,2Joining(J)segments:61,13Then

6、eedtopairandchainstoformabindingsitedoublesthepotentialfordiversityJUNCTIONALDIVERSITYAdditionofnon-templateencoded(N)andpalindromic(P)nucleotidesatimprecisejointsmadebetweenV-D-JelementsSOMATICMUTATIONISNOTUSEDTOGENERATEDIVERSITYINTcRTcROrganisationofTc

7、RgenesL&Vx70-80CTcRD1Jb1x6C1D2Jb2x7C2TcRgenessegmentedintoV,(D),J&Celements(VARIABLE,DIVERSITY,JOINING&CONSTANT)CloselyresembleIggenes(a~IgLandb~IgH)ThisexampleshowsthemouseTcRlocusJx61L&Vx52TcRagenerearrangementbySOMATICRECOMBINATIONSplicedTcRmRNAGe

8、rmlineTcRVnJCV2V1RearrangedTcR1°transcriptRearrangementverysimilartotheIgLchainsRearrangedTcR1°transcriptSplicedTcRmRNAL&Vx52D1JC1D2JC2GermlineTcRTcRbgenerearrangementSOMATICRECOMBINATIO