Facilitated antigen uptake and timed exposure to TLR ligands dictate the antigen‐presenting potential of plasmacytoid DCs

Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society

关键词: dentritic cells;    antigen processing;    influenza;    OVA;   

DOI  :  10.1189/jlb.0610342

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

Subsetsofantigen‐presentingcDCshaveadifferentialcapacitytopresentexogenousandendogenousproteinantigenstoCD4+and/orCD8+Tlymphocytes,dependingonexpressionofantigen‐uptakereceptors,processingmachinery,andmicrobialinstruction.pDCsarealsocapableofantigenpresentation,buttheconditionsunderwhichtheydothishavenotbeensystematicallyaddressed.HighlypurifiedcDCsandpDCswereexposedtoexogenous,solubleOVApeptideorwholeprotein.Alternatively,theyweremadetoexpresscytoplasmicorendosomalOVAbyretroviraltransductionorbyinfectionwithinfluenzaviruscontainingOVAepitopes.LikecDCs,pDCsexpressedtheMHCIprocessingmachineryandcouldpresentendogenousorcross‐presentexogenousOVAtoCD8+Tcells,providedtheyhadbeenstimulatedbyCpGmotifTLR9ligandsorbyinfluenza.UnlikecDCs,thecross‐primingactivityofpDCswasenhanced,notdecreased,bysimultaneousTLRstimulation.ProcessingandpresentationofexogenousOVAtoCD4+TcellsrequiredTLR9ligationpriortoantigenencounterandadditionofOVA‐specificIgs.Thesestimuliup‐regulatedcriticalMHCIIprocessingmachineryandenhancedroutingtoacidicendosomalorganellesinaFcγRII‐dependentmanner.EndogenousantigenwasnotpresentedtoCD4+TcellswhenexpressedinthecytoplasmofpDCsbyretrovirusorcontainedininfluenza,unlessanIi‐chain‐derivedendosomalroutingsignalwaspresent.Thus,timingofTLRligationandfacilitatedantigenuptakedictatethepotentialofpDCstopresentendogenousorexogenousantigenbyinfluencingendosomaltrafficandantigen‐processingmachinery...

【 授权许可】

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