Characterization of preproinsulin (ppins)-specific CD8 T-cell responses in novel models of autoimmune diabetes [Elektronische Ressource] / vorgelegt von Helen Beate Brosi

Description

vorgradesiUzlmren-zurMedizinischebiol.FakultätakultätBeateZentrum2010füretesInneredesMedizinHumanbiologieIderLeiter:nischenProf.UniversitätDr.vonmed.gebGuidonAddlerabChaDissertationracterizationErlangungofDoktopderrep(Dr.roinsulinhum.)(ppins)-spmedieciciCD8FTdercellUlmresprgelegtonsesHeleninBrosinovelomoidelsAachenofUniversitätautoimmuneAmtierenderUwPDekagan:2.Profof..KnippschildDr.Promotion:Klaus-MichaeleckDebatinBerichterstatter:1.rBerichterstatter:Dr.PerTof.derDr.18.06.2010ReinholdSchirmb.and.Abb.reviations.VIIVI.I.1.Intro.duction.1.1.1.Diab.etes11melli.tusHistology.....14.on.antigen-sp.......Generation...racterization.......glucose.......Lympho...ma...r..............181.2cellT.yp.es1.Diab.etes..ression.....mi.......of...............2.11.......Generation.chimeras.....of.cell...2.14.binding....1n1.3TT.yp.e.1.Diab.etes.in.mice.moCelldelsof.........9.exp.n...........2.7.antigen...........Immunization....2.1.4.DNA.immunization....2.9.o...........3...................ration.............14.b.ro..2.1.5.Co-stimulato.ry.andTco-inhibitocytesryCD8signals......

Sujets

• Gesundheit

Informations

• Publié par: universitat_ulm
• Publié le: 01 janvier 2010
• Nombre de lectures: 17
• Langue: English
• Poids de l'ouvrage: 10 Mo

Extrait

rgelegtUniversit?tderUablmi-iMedizinischeErlangungFhum.)akult?tderZentrumBrosif?rdInnereDissertationMedizinDoktoI(Dr.Leiter:mediProf.FDr.Ulmmed.HelenGuidooAAachendleriChaetesracterizationzurofdesprgradesrepHumanbiologieroinsulinbiol.(ppins)-spdereciczCD8nischenTakult?tcellUniversit?trespvoonsesvoninBeatenovelgebmorendelsnof2010autoimmuneeckAmtierendereDekran:derProfBerichterstatter:.Dr.Dr.TKlaus-Michael18.06.2010Debatin2.1.PBerichterstatter:of.PUwrKnippschildof.agDr.Promotion:ReinholdSchirmbb
.Abbstablereviations.VI.I.I.1.Intro.duction.1.1.1.Diab.etes.melli.tusof.Determination...13.2.12.ransfers.anities.cell.......re...exp...................w...T.14...ati....1.1.2.Tlinesyp.e.12.6Diabplasmidsetes....Cha...............d.....2.10.........of.......one.......o.....ati..1.1.315Teciyp.eIV1.Diab.etes.in.mice.mo.dels2.5.Generation.lines.........of.sio...........9.of...........2.8.ce2.1.4.DNA.immunization......12.blo.levels.........1...................Prepa.cytes.............of.r2.1.5.Co-stimulato.ry.and.co-inhibito2.13ryLymphosignalspuried.s.......Determi.ofContents...........Determi.of.CD8........3.1.6.Pro.cessing.of.diab.etic.epitop.es.fo.r.MHC-class.I8-rCellestrictedandpofresentationcell..6.1.7.Aim.of.the.study....9.Generation.exp.s.n.......................2.7.racterization.antigen.ression..................7112ImmunizationMaterialmiand.Metho.ds.8.2.1.Chemicals..................2.9.of.o.glucose.....................3.Histology..................8.2.2.Media.and.Buers........2.11.ration.Lympho.........................14.Generation.b.ma.ro.chimeras..........8.2.3.Mice....14.T.of.cytes.r.CD8.cell...............2.14.n.on.K.binding.....................2.15.n.on.antigen-sp.c.T8frequencies2.4.Synthetic.p.eptides..15...Contentsrimi2.16.Statistics........46.regulates...Media...cells.....e.....Bibliography.........46.e-sp.p.........is.strong...48.....5.6016.3.Results.17.3.1.The.B7.1.m.ouspublicationseEcientmoofdelCD8.ER-asso.cessing.................EAD.re.b.........PD-1/PD-L1...........ry.App.and17.3.2.Pro.cessing.of.insulin....Buer.................List.V.4.1.p.ng.epitop.ecic.T.requires.ciated.ro..............24.3.3.Selective.analysis.of.the.eecto.r.phas.e.of4.2EADinduction.supp.ss.d.y.antigens...............4.3.co-inhibition31EAD3.4.Cha.racterization.of.ppins-sp.ecic.immuno.dominance.hiera49rchiesSumma.51.53.endix.Chemicals.Reagents32.3.5.The.B6.mouse.mo.del................60.and.................................62.of38644Discussionb
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........P-B7..Schematic...Induction.with....4.1.2lotCD80pligands.ppins.....Screeni.r...b.....fusion.....of.resentation.30...T.....32...pCI/ppins.ti.......3.12.epitop.....eGFP-exp..5c3.1.Map.of3.15ppins.p.....mice.29.constructs....tes.....y...3.20.........EAD.....r...33...epitop...3.24.........of17ER-ta3.2.Induction.of.EAD.in26RIP-B7.1resentationmicconstructs.e.with.pCI/ppins.3.14.of.roteins..........estern.insulin/GFP......18.3.33.16InductioninofInsulin/GFPEAD.isSchematicsexmutantindep.endent.....Diab.of.RIP-B7.1.....30.EAD.transferred.......of............18.3.4.InductionInductionofRIP-B7.1EAD.in.RIP-B7.1.mic33egisesCD8ATRcellmice.depDetermiendent.of.y..........19.3.5.Histological.analysis.oflls.diab.etes.dev.elopment25inInductionRIP-B7.1EADmice.y.rgeted.es.......20.3.6.Screening.fo.r.e3.13ppioftopressiones.of.diab.etic.RIP-B7.1.mic27e.Lo.alization.insulin/GFP.p.................28.W21B3.7ofDeterminationfusionofroteins.K...avidit.y.fo.r.A..28.InductionepitopEADe.RIP-B7.1.with.fusion.roteins....3.17.p.of.insulin............213.183.8eChaincidencesracterizationmutantofinamice.cross-reactive.A...immunization..DNA.1.13.19epitopofebvaadoptivelyrCD8iant.cells..........31.Map22ppins3.9AKinetic.analysis.of.diab.etes.deve.lopment.in.RIP-B7.1.mice.............3.21.of23in3.10miceExppCI/ppinsressionAof.ppins.in.HEK2.93.cells.3.22.n.fo.epitop.of.....-immunized.I.1...3.23.na.on.K.avidit.fo.B...e.24.3.11...........34.B.Induction-tetramers.of.EAD.b.y.K.Figures./A.of.List.....VI.T.ce.mono-sp34ecicCD8 12 21
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lpCI/ppinsofA.andppCI/ppins..ell.....mice..PD-L1.PD-L1.....pCI/ppins-immunized...4035etes3.26.Co-immunizationofof.pCI/ppinsInductionandspCI/S...fo.List...Induction.VI.B6.....Histologic.of.in.....3.32.in.mice.36.3.2742Co-immunizationEADofmicepCI/ppins-OTVendent.A.of3.34Co-immunizationepitop.etic.......43.EAD...anti-PD-L1.re-immunized.mice..........3.31.a.analysis37diab3.28developmentInductionB6of.EAD.in.B6.mice41withInductionpCI/ppins.EAD.pCI/ppins-immunized.Figures.........3.33.of.in.of.i.CD8.c.dep..38.3.29.Induction43ofScreeningEADrbesydiabadoptivelyPD-L1transferredmice.CD8.T.cells.from.B6.mice..3.253.35mice.of.in.PD-1...39.3.30.Induction.of44EADIin
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