Differential Requirement for Cathepsin D for Processing of the Full Length and C-Terminal Fragment of the Malaria Antigen MSP1 英文参考文献.docVIP

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Differential Requirement for Cathepsin D for Processing of the Full Length and C-Terminal Fragment of the Malaria Antigen MSP1 英文参考文献.doc

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Differential Requirement for Cathepsin D for Processing of the Full Length and C-Terminal Fragment of the Malaria Antigen MSP1 英文参考文献

DifferentialRequirementforCathepsinDforProcessing oftheFullLengthandC-TerminalFragmentofthe MalariaAntigenMSP1 CalogeroTulone1.,Anne-MaritSponaas2.,Eun-AngRaiber3,AletheaB.Tabor3,JeanLanghorne2, BennyM.Chain1* 1DivisionofInfectionandImmunity,UniversityCollegeLondon,London,UnitedKingdom,2DivisionofParasitologyMRCNationalInstituteofMedicalResearch,London, UnitedKingdom,3DepartmentofChemistry,UniversityCollegeLondon,London,UnitedKingdom Abstract MerozoiteSurfaceProtein1isexpressedonthesurfaceofmalariamerozoitesandisimportantforinvasionofthemalaria parasiteintoerythrocytes.MSP1-specificCD4Tcellresponsesandantibodycanconferprotectiveimmunityinexperimental modelsofmalaria.InthisstudyweexplorethecontributionsofcathepsinsDandE,twoasparticproteinasespreviously implicatedinantigenprocessing,togeneratingMSP1CD4T-cellepitopesforpresentation.TheabsenceofcathepsinD,a lateendosome/lysosomalenzyme,isassociatedwithareducedpresentationofMSP1bothfollowinginvitroprocessingof theepitopeMSP1frominfectederythrocytesbybonemarrow-deriveddendriticcells,andfollowinginvivoprocessingby splenic CD11c+ dendriticcells.By contrast, processingandpresentationofthesolublerecombinant proteinfragment of MSP1isunaffectedbytheabsenceofcathepsinD,butisinhibitedwhenbothcathepsinDandEareabsent.Theroleof different proteinases in generating the CD4 T cell repertoire, therefore, depends on the context in which an antigen is introducedtotheimmunesystem. Citation:TuloneC,SponaasA-M,RaiberE-A,TaborAB,LanghorneJ,etal.(2011)DifferentialRequirementforCathepsinDforProcessingoftheFullLengthand C-TerminalFragmentoftheMalariaAntigenMSP1.PLoSONE6(10):e24886.doi:10.1371/journal.pone.0024886 Editor:NirbhayKumar,TulaneUniversity,UnitedStatesofAmerica ReceivedFebruary23,2011;AcceptedAugust23,2011;PublishedOctober28,2011 Copyright: ? 2011 Tulone et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricteduse,distribution,andreproductioninanymediu