Adaptive Immunity against Leishmania Nucleoside Hydrolase Maps Its C-Terminal Domain as the Target of the CD4+ T Cell–Driven Protective Response 英文参考文献.docVIP

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Adaptive Immunity against Leishmania Nucleoside Hydrolase Maps Its C-Terminal Domain as the Target of the CD4+ T Cell–Driven Protective Response 英文参考文献.doc

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AdaptiveImmunityagainstLeishmaniaNucleosideHydrolaseMapsItsC-TerminalDomainastheTargetoftheCD4TCell–DrivenProtectiveResponse英文参考文献

AdaptiveImmunityagainstLeishmaniaNucleoside HydrolaseMapsItsC-TerminalDomainastheTargetof theCD4+TCell–DrivenProtectiveResponse DirleiNico1,CarlaClaser2¤,GulnaraP.Borja-Cabrera1,LuizR.Travassos3,MarcosPalatnik4,Ireneda SilvaSoares5,MauricioMartinsRodrigues2,ClarisaB.Palatnik-de-Sousa1* 1DepartamentodeMicrobiologiaGeral,InstitutodeMicrobiologiaProf.PaulodeGo′es,UniversidadeFederaldoRiodeJaneiro(UFRJ),RiodeJaneiro,Brazil,2Centro InterdisciplinardeTerapiaGe?nica,UniversidadeFederaldeSa?o Paulo(UNIFESP),Sa?o Paulo,Brazil,3UnidadedeOncologiaExperimental,UniversidadeFederaldeSa?o Paulo, Sa?o Paulo, Brazil, 4Hospital Universita′rio Clementino Fraga Filho-Faculdade de Medicina, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil, 5DepartamentodeAna′lises Cl?′nicaseToxicolo′gicas,UniversidadedeSa?o Paulo,Sa?o Paulo,Brazil Abstract Nucleosidehydrolases(NHs)showhomologyamongparasiteprotozoa,fungiandbacteria.Theyarevitalprotagonistsinthe establishmentofearlyinfectionand,therefore,areexcellentcandidatesforthepathogenrecognitionbyadaptiveimmune responses. Immune protection against NHs would prevent disease at the early infection of several pathogens. We have identifiedthedomainoftheNHofL.donovani(NH36)responsibleforitsimmunogenicityandprotectiveefficacyagainst murinevisceralleishmaniasis(VL).UsingrecombinantgeneratedpeptidescoveringthewholeNH36sequenceandsaponin we demonstrate that protection against L. chagasi is related to its C-terminal domain (amino-acids 199–314) and is mediatedmainlybyaCD4+TcelldrivenresponsewithalowercontributionofCD8+Tcells.Immunizationwiththispeptide exceedsin36.73612.33%theprotectiveresponseinducedbythecognateNH36protein.IncreasesinIgM,IgG2a,IgG1and IgG2b antibodies, CD4+ T cell proportions, IFN-c secretion, ratios of IFN-c/IL-10 producing CD4+ and CD8+ T cells and percentsofantibodybindinginhibitionbysyntheticpredictedepitopesweredetectedinF3vaccinatedmice.Theincreases in DTH and in ratios of TNFa/IL-10 CD4+ producing cells were h