Apoptotic Cells Deliver Processed Antigen to Dendritic Cells for Cross-Presentation.docVIP

o Openaccess,freelyavailableonline PL S BIOLOGY ApoptoticCellsDeliverProcessedAntigen toDendriticCellsforCross-Presentation Nathalie E.Blache`re1,Robert B.Darnell2,3,Matthew L.Albert1,4* 1Laboratoired’ImmunobiologiedesCellulesDendritiques,InstitutPasteur,Paris,France,2TheLaboratoryofMolecularNeuro-oncology,TheRockefellerUniversity,New York,NewYork,UnitedStatesofAmerica, 3HowardHughesMedicalInstitute,TheRockefellerUniversity,NewYork,NewYork,UnitedStatesofAmerica, 4InstitutNational delaSante′ etdelaRechercheMe′dicale(INSERM)AV0201,Paris,France Antigen derived from engulfed apoptotic cells can be cross-presented by dendritic cells (DCs) for the generation of major histocompatibility class I/peptide complexes. While the early events of recognition and internalization of the dyingcellhavebeencharacterized,theantigen-processingpathwayorpathwaysremainunknown.Weestablisheda mouse model assaying for the activation of polyclonal T cells reactive to antigen derived from apoptotic cells, and demonstrated two distinct pathways for the trafficking of exogenous epitopes. In the first, exogenous antigen is dependentontheDC’sexpressionofafunctionaltransporterassociatedwithantigenprocessing(TAP).Surprisingly, we found evidence that a second pathway exists in which transfer of processed antigen from the dying cell allows formation of major histocompatibility class I/peptide complexes in TAP-deficient DCs. In vivo data suggest that in situations ofstress (e.g.,viral infection), this latter pathwaymaybemore efficient, illustrating that dying cells may preselectimmunologicallyimportantantigenicdeterminants. Citation:Blache`reNE,DarnellRB,AlbertML(2005)Apoptoticcellsdeliverprocessedantigentodendriticcellsforcross-presentation.PLoSBiol3(6):e185. antigenboundtolatexbeads[16,17],derivedfrominternal- izedimmunecomplexes[18]orwholeprotein[19],doesnot Introduction Apoptosis is considered the primary means by which physiologic cell death occurs [1]. The fate of apoptotic mater