Mathematical, Computational and Experimental T Cell Immunology PDF
Preview Mathematical, Computational and Experimental T Cell Immunology
Carmen Molina-París Grant Lythe Editors Mathematical, Computational and Experimental T Cell Immunology Mathematical, Computational and Experimental T Cell Immunology Carmen Molina-París (cid:129) Grant Lythe Editors Mathematical, Computational and Experimental T Cell Immunology Editors CarmenMolina-París GrantLythe DepartmentofAppliedMathematics, DepartmentofAppliedMathematics, SchoolofMathematics SchoolofMathematics UniversityofLeeds UniversityofLeeds Leeds,UK Leeds,UK ISBN978-3-030-57203-7 ISBN978-3-030-57204-4 (eBook) https://doi.org/10.1007/978-3-030-57204-4 ©SpringerNatureSwitzerlandAG2021 Thisworkissubjecttocopyright.AllrightsarereservedbythePublisher,whetherthewholeorpartof thematerialisconcerned,specificallytherightsoftranslation,reprinting,reuseofillustrations,recitation, broadcasting,reproductiononmicrofilmsorinanyotherphysicalway,andtransmissionorinformation storageandretrieval,electronicadaptation,computersoftware,orbysimilarordissimilarmethodology nowknownorhereafterdeveloped. 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ThisSpringerimprintispublishedbytheregisteredcompanySpringerNatureSwitzerlandAG Theregisteredcompanyaddressis:Gewerbestrasse11,6330Cham,Switzerland toFederico-icoandSofía-pía, maytheyalwaysbegood,happyandfree. + StimulationofnaiveCD4 TcellswithPMAandIonomycin. + NaiveCD4 TcellsfromaBALB/cmousewereisolatedandapproximately50,000 cells were seeded in a U-bottomed 96 well plate. The cells were activated with 10ng/mLofPhorbol12-myristate13-acetateand0.1μMIonomycin.Thispicture wastaken36hourspost-activation. vii Contents 1 CytokineReceptorSignalingandCD4/CD8LineageChoice duringTCellDevelopmentintheThymus.............................. 1 MeganA.LuckeyandJungHyunPark 2 AnAgent-BasedModelofTHelperCellFateDecisionsinthe Thymus ...................................................................... 21 Sahamoddin Khailaie, Philippe A. Robert, and Michael Meyer-Hermann 3 ModellingNaiveTCellHomeostasis..................................... 45 BenedictSeddon,SanketRane,andAndrewJ.Yates 4 Mechanistic Models of CD4 T Cell Homeostasis and ReconstitutioninHealthandDisease .................................... 65 JoannaLewisandJosephF.Standing 5 ModelingtheDynamicsofCD4+TCellsinHIV-1Infection ......... 81 RuyM.Ribeiro 6 Modelling the Response to Interleukin-7 Therapy in HIV-InfectedPatients...................................................... 95 RodolpheThiébaut,LauraVillain,ChloéPasin, andDanielCommenges 7 ModelingImmunopathologyDuringPersistentViralInfections...... 109 VeronikaI.Zarnitsyna,PhilipL.F.Johnson,JosephN.Blattman, andRustomAntia 8 DelayedDifferentiationMakesManyModelsCompatiblewith + DataforCD8 TCellDifferentiation.................................... 121 AridamanPanditandRobJ.deBoer 9 Inferring Differentiation Order in Adaptive Immune ResponsesfromPopulation-LevelData.................................. 133 AlexanderS.Miles,PhilipD.Hodgkin,andKenR.Duffy ix x Contents 10 Experimental and Mathematical Approaches to Quantify RecirculationKineticsofLymphocytes .................................. 151 VitalyV.GanusovandMichioTomura 11 ThePublicFaceandPrivateLivesofTCellReceptorRepertoires... 171 PradyotDashandPaulG.Thomas 12 PopulationDynamicsofImmuneRepertoires........................... 203 JonathanDesponds,AndreasMayer,ThierryMora, andAleksandraM.Walczak 13 MathematicalModellingofTCellActivation........................... 223 NicolaC.TrendelandOmerDushek 14 Agent-BasedModelofHeterogeneousT-CellActivationinVitro..... 241 Shamik Majumdar, Carmen Molina-París, Dipankar Nandi, and GrantLythe 15 CTLA-4-MediatedLigandTrans-Endocytosis: AStochasticModel......................................................... 257 LuisdelaHiguera,MartínLópez-García,GrantLythe, andCarmenMolina-París 16 Automated Gating and Dimension Reduction of High-DimensionalCytometryData....................................... 281 SharonX.Lee,GeoffreyJ.McLachlan,andSaumyadiptaPyne Index............................................................................... 295 Chapter 1 Cytokine Receptor Signaling and CD4/CD8 Lineage Choice during T Cell Development in the Thymus MeganA.LuckeyandJungHyunPark 1.1 Introduction TcellimmunityiscontrolledbytwomajorsubsetsofTcellsthatcanbeidentified bytheirdistinctexpressionofthecoreceptormoleculesCD4andCD8.Tcellsthat expresstheCD4coreceptorrecognizepeptideantigensinthecontextofMHCclass IImoleculesandprovidehelperfunctions.TcellsthatexpresstheCD8coreceptor, in contrast, react with peptide antigens in the context of MHC class I and exhibit cytolytic activities [50, 82]. Notably, there is a remarkable correlation between coreceptor expression and T cell function, such that CD4 coreceptor expression marks helper lineage T cells, whereas CD8 coreceptor expression is associated withcytolyticactivity.TheassociationbetweencoreceptorphenotypeandTeffector functionisthoughttobeimposedduringTcelldevelopmentinthethymus,where immature thymocytes that express both CD4 and CD8 coreceptor molecules, i.e., + + CD4 CD8 double-positive (DP) cells, make lineage decision into either CD4 single-positive (CD4SP) or CD8 single-positive (CD8SP) T cells [8, 28, 88]. The process of CD4 versus CD8 cell fate decision has fascinated immunologists for a long time. However, deciphering the molecular basis of this process turned out to be a daunting task. A major obstacle is the multiplicity of events that occur at the sametimewhenCD4versusCD8lineagecommitmentismade.Mostprominently, CD4/CD8lineagechoicecoincideswiththeTcellreceptor(TCR)-inducedpositive selection, which upregulates TCR expression. However, positive selection also induces changes in coreceptor expression, so that the exact cellular phenotype at lineagedecisionhadremainedobscureandconfusing[88]. M.A.Luckey·J.H.Park((cid:2)) ExperimentalImmunologyBranch,CenterforCancerResearch,NationalCancerInstitute, NationalInstitutesofHealth,Bethesda,MD,USA e-mail:[email protected] ©SpringerNatureSwitzerlandAG2021 1 C.Molina-París,G.Lythe(eds.),Mathematical,ComputationalandExperimentalTCell Immunology,https://doi.org/10.1007/978-3-030-57204-4_1 2 M.A.LuckeyandJ.H.Park Because TCR specificity imposes MHC restriction that is further matched with the appropriate CD4 or CD8 coreceptor expression, classically, CD4/CD8 lineage choice has been considered a developmental event that is primarily controlled by TCRsignaling[5,28,36,113].However,TCRsignalingalonecannotsatisfactorily explain the entire process of CD4 versus CD8 lineage commitment. In fact, it became evident thatcellfatedecisioninthethymus requiresadditional regulatory pathways,workinginconcertwithTCRsignalingtodeterminethelineagechoice. Aseriesofexperimentalresultsfollowedbyfurthergeneticevidencerevealedthis requirementtobethesignalingbyintra-thymiccytokines.Thus,cytokinesignaling activity specifies CD4/CD8 lineage fate during positive selection and further imposes T cell function and promotes maturation of post-selection thymocytes [10, 67, 74, 117]. In this article, we aimed to review our current understanding of CD4/CD8lineagechoiceduringTcelldevelopmentandtohighlightrecentfindings ontheroleofcytokinereceptorsignalinginthisprocess. 1.2 TCellDevelopmentandCD4/CD8LineageChoice inthe Thymus Because both CD4SP and CD8SP cells originate from DP thymocytes, early attempts to explain CD4 versus CD8 lineage choice were proposed around the ideathatlineagedecisionwasmadebyselectivelyextinguishingtheexpressionof one or the other coreceptor [23, 103]. The molecular identity of the signals that would instruct the termination of either CD4 versus CD8 coreceptor expression, however,remaineddisputed.Differenthypothesesandtheirvariationsofstochastic orinstructionalmechanismswereputforwardtoexplaintheprogressionofDPinto SPcells[4,5,7,28,103].BecauseforcedexpressionofanMHCclassI(MHC-I) restrictedTCRresultsinthegenerationofCD8Tcells,butMHCclassII(MHC-II)- restricted TCR transgenes produce CD4 T cells, evidently, lineage fate is encoded inthespecificityoftheTCR.However,itwasnotknownhowthisinformationwas extracted by the immune system and then translated into lineage specification. An attractivemodelthathasbeenfavoredforalongtimeproposedthatMHC-I-versus MHC-II-restricted TCRs differ in their signaling strength, such that strong TCR signalsterminateCD8expressionanddriveCD4lineagechoice,whereasweakTCR signals terminate CD4 expression and impose CD8 lineage fate [5, 28, 36, 103]. WithregardtothemolecularbasisofdistinctTCRsignalingstrength,itwasnoted thatCD4coreceptors,whichpreferentiallyassociatewithMHC-II-restrictedTCR, bindssignificantlylargeramountsofthetyrosinekinaseLckthanCD8coreceptors, which associates with MHC-I-specific TCR [97, 99, 100]. Thus, the “strength-of- signal”modelpositsthatCD4/CD8lineagechoiceismadeattheDPstage,where quantitativedifferencesinTCRsignalsinstructtheexpressionofanMHC-matched coreceptorthatassociateswiththesignal-transducingTCR[5,36,37,56,108].
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