A Conserved Multi-Gene Family Induces Cross-Reactive Antibodies Effective in Defense against Plasmodium falciparum 英文参考文献.docVIP
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A Conserved Multi-Gene Family Induces Cross-Reactive Antibodies Effective in Defense against Plasmodium falciparum 英文参考文献
AConservedMulti-GeneFamilyInducesCross-Reactive
AntibodiesEffectiveinDefenseagainstPlasmodium
falciparum
Subhash Singh1¤*, Soe Soe1, Simon Weisman1, John W. Barnwell2, Jean Louis Pe′rignon1 , Pierre
Druilhe1*
1Bio-medicalParasitologyUnit,InstitutPasteur,Paris,France,2MalariaBranch,DivisionofParasiticDiseases,CentersforDiseaseControlandPrevention,Atlanta,Georgia,
UnitedStatesofAmerica
Abstract
Background: Two related merozoite surface proteins, MSP3 and MSP6, have previously been identified as targets of
antibody-dependentcellularinhibition(ADCI),aprotectivemechanismagainstPlasmodiumfalciparummalaria.BothMSP3
and MSP6 share a common characteristic small N-terminal signature amino-acid stretch (NLRNA/G), a feature similar to
MSP3-likeorthologsidentifiedinotherhumanandprimatemalariaparasites.
Methods/Results: Thissignature amino-acid sequence led tothe identification ofeight ORFs contiguously located on P.
falciparumchromosome10.Oursubsequentinvestigationsontheirexpression,localization,sequenceconservation,epitope
sharing,immunogenicityandthefunctionalroleofantibodiesindefensearereportedhere.SixmembersofP.falciparum
MSP3-multigenefamilysharesimilarsequenceorganizationwithintheirC-terminalregions,aresimultaneouslyexpressedas
merozoitesurfaceproteinsandarehighlyconservedamongparasiteisolates.Eachoftheseproteinsisatargetofnaturally
occurringantibodieseffectiveatparasitekillinginADCIassays.Moreover,bothnaturallyoccurringantibodiesandthose
generatedbyimmunizationdisplaycross-reactivitywithothermembersofthefamilyandexhibitvariedbindingavidities.
Conclusions/Significance: The unusual characteristics of the MSP3 multi-gene family lead us to hypothesize that the
simultaneous expression of targets eliciting cross-reactive antibody responses capable of controlling parasite densities
couldrepresentanimmuneprocessselectedthroughevolutiontomaintainhomeostasisbetweenP.falciparumandhuman
hosts;aprocessthatallowsthecontinuoustransmissionoftheparasitewithoutkillingthehost.Ourobservat
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