抗 原 加 工 提 呈Antigen Processing and Presentation PPT课件

抗原加工提呈（AntigenProcessingandPresentation）张勇TcellsdonotrecognizenativeantigensAntigensmustbeprocessedinordertoberecognizedbyTcellsTcellresponseNoTcellresponseNoTcellresponseNoTcellresponseNoTcellresponseAgprocessingandpresentationSinceallcellsexpressingeitherclassIorclassIIMHCmoleculescanpresentpeptidestoTcells,strictlyspeakingtheyallcouldbedesignatedasAntigenPresentingCells(APC).However,………………..Targetcells:CellsthatdisplaypeptidesassociatedwithclassIMHCmoleculestoCD8+Tccellsarereferredtoastargetcells.Professionalantigenpresentingcells(APC):CellsthatdisplaypeptidesassociatedwithclassIIMHCmoleculestoCD4+ThcellsarecalledAPC.APCs:highlyspecializedcellsUptakeandprocessantigensExpressco-stimulatorymolecules(B7)ExpressclassIIMHCmoleculesPresentantigenicpeptidetoCD4+T-cellthemainAPCsare:dendriticcells,macrophagesandBcells.The3typesofAPCsConstitutivelyexpressahighlevelofMHCIIandtheco-stimulatoryprotein,B7.themosteffectiveAPCConstitutivelyexpressclassIIMHCbutmustbeactivatedtoproduceB7.mustbeactivatedbytheprocessofphagocytosisbeforeexpressingclassIIMHCandB7.1.dendriticcell(DC)discoveredin1973Tissue–residentDCsurfacereceptorsrecognizemicrobesImmatureDC(iDC)migratetolocallymphnodesWithinlymphnodesDCpresentantigenstoTcellsinMHCmoleculesmatureDC(mDC)iDCmDCLowlevelsofclassIIMHCandB7StronglyinternalizeantigensbuthavenopresentationabilityhighlevelsofclassIIMHCandB7Stronglypresentantigensbutcan’tuptakeantigensmonocyte：bloodmacrophage：tissue2.macrophage(M) receptors mannosereceptor LPSreceptor CRandFcRspecializedtointernalizeparticleantigensMHCandco-stimulatorymoleculesclassⅡMHC：inducibleexpressedafterphagocytosisB7：inducibleexpressedafterphagocytosis BCR(smIg):takeupsolubleantigensefficintly ConstitutivelyexpressclassⅡMHC InducibleexpressionofB73.BlymphocyteThepropertiesofvariousAPCsantigenprocessingproteinantigenisdegradedintopeptideantigenpresentationassociationofpeptidewithMHCandtransportationofMHC-peptidecomplextothecellmembraneAntigenprocessingandpresentationendogenousantigens：proteinsthataresynthesizedwithinthecytoplasmofthecell.Examples:viralproteins,tumorantigensexogenousantigens：antigensoriginateoutsidethecell.Examples:bacteriaproteinsProcessingandPresentationofEndogenousAntigens(MHCclassIpathway)DegradationintheproteasomeThecomponentsoftheproteasomeincludeMECL-1,LMP2,LMP7LMP2&7encodedintheMHCProteasomecleavesproteinsafterhydrophobicandreleasespeptidesintothecytoplasmCytoplasmiccellularproteins,includingnon-selfproteinsaredegradedcontinuouslybyamulticatalyticproteaseof28subunitsENDOPLASMICRETICULUMCYTOSOLPeptideantigensproducedinthecytoplasmarephysicallyseparatedfromnewlyformedMHCclassITransportersassociatedwithantigenprocessing(TAP1&2)Transporterhaspreferencefor>8aminoacidpeptideswithhydrophobicCtermini.CalnexinbindstonascentclassIchainuntil2-mbindsB2-mbindsandstabilisesfloppyMHCTapasin,calreticulin,TAP1&2formacomplexwiththefloppyMHCCytoplasmicpeptidesareloadedontotheMHCmoleculeandthestructurebecomescompactMaturationandloadingofMHCclassIFateofMHCclassIThepresentationofClassIMHC/peptidebyatargetcelltoaCD8+TccellresultsintheproliferationandsubsequentdifferentiationofaTcintoakiller/effectorcell.TheTccanthenparticipateinTARGETCELLKILLING.Targetcell“kissofdead”ProcessingandPresentationofExogenousAntigens(MHCclassIIpathway)YPinocytosisPhagocytosisMembraneIgreceptormediateduptakeUptakeofexogenousantigensComplementreceptormediatedphagocytosisFcreceptormediatedphagocytosisUptakemechanismsdirectantigenintointracellularvesiclesforexogenousantigenprocessingProteasesproduce15~30aminoacidslongpeptidesfromantigensExogenouspathwayProteinantigensInendosomeCathepsinB,DandLproteasesareactivatedbythedecreaseinpHNeedtopreventnewlysynthesised,unfoldedselfproteinsfrombindingtoimmatureMHCInvariantchainstabilisesMHCclassIIbynon-covalentlybindingtotheimmatureMHCclassIImoleculeandforminganonomericcomplexIntheendoplasmicreticulumMHCclassIImaturationandinvariantchainClassIIassociatedinvariantchainpeptide(CLIP)(Ii)3complexesdirectedtowardsendosomesbyinvariantchainCathepsinLdegradesInvariantchainCLIPblocksgrooveinMHCmoleculeMHCClassIIcontainingvesiclesfusewithantigencontainingvesiclesRemovalofCLIP?Howcanthepeptidestablybindtoafloppybindingsite?CompetitionbetweenlargenumberofpeptidesHLA-DMcatalysestheremovalofCLIPMIICcompartmentHLA-DMReplacesCLIPwithapeptideantigenusingacatalyticmechanismMIICcompartmentsortspeptide-MHCcomplexesforsurfaceexpressionorlysosomaldegradationSurfaceexpressionofMHCclassII-peptidecomplexesTheresultofClassIIMHC/peptidebyanAPCtoaCD4+Thcellis:ACTIVATIONandPROLIFERATIONoftheThcellandthen“help”otherimmuno-cellstoactivate.Separateantigen-presentingpathwaysareutilizedforendogenous(green)andexogenous(red)antigens.ThemodeofantigenentryintocellsandthesiteofantigenprocessingdeterminewhetherantigenicpeptidesassociatewithclassIMHCmoleculesintheroughendoplasmicreticulumorwithclassIImoleculesinendocyticcompartments.内源性和外源性抗原加工途径特点比较 特点 内源性抗原加工途径 外源性抗原加工途径 提呈抗原肽的MHC分子 I类分子 II类分子 应答的T细胞 CD8+T细胞 CD4+T细胞 抗原来源 内源性 外源性 抗原肽产生部位 胞内蛋白酶体 内体、溶酶体 MHC荷肽部位 内质网腔 CIIV或MIIC 伴随蛋白 钙联素，TAP，tapasin 钙联素，Ii链 提呈细胞 所有有核细胞 专职APC本章 要求 对教师党员的评价套管和固井爆破片与爆破装置仓库管理基本要求三甲医院都需要复审吗 ：1.掌握APC的概念、种类及生物学功能。2.掌握内源性和外源性抗原加工提呈的过程。3.掌握下列常用名词：抗原加工提呈、APC、内源性抗原、外源性抗原