Antigen-antibody immune complexes empower dendritic cells to efficiently prime specific CD8+ CTL responses in vivo.
Dendritic cells (DCs) require a maturation signal to acquire efficient CTL-priming capacity. In vitro FcgammaR-mediated internalization of Ag-Ab immune complexes (ICs) can induce maturation of DCs. In this study, we show that IC-induced DC maturation in vitro enables DCs to prime peptide-specific CD8+ CTLs in vivo, independently of CD4+ Th cells. Importantly, OVA/anti-OVA IC-treated DCs not only primed CD8+ CTLs to an exogenously loaded peptide nonrelated to OVA, but also efficiently primed CTLs against the dominant CTL epitope derived from the OVA Ag present in the ICs. Our studies show that ICs fulfill a dual role in priming of CD8+ CTL responses to exogenous Ags: enhancement of Ag uptake by DCs and activation of DCs, resulting in "license to kill." These findings indicate that the presence of specific Abs can crucially affect the induction of cytotoxic cellular responses.
Schuurhuis
Danita H
DH
Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Albinusdreef 2, 2300 RC Leiden, The Netherlands.
Ioan-Facsinay
Andreea
A
Nagelkerken
Bas
B
van Schip
Jolien J
JJ
Sedlik
Christine
C
Melief
Cornelis J M
CJ
Verbeek
J Sjef
JS
Ossendorp
Ferry
F
D000818:Animals; D017951:Antigen Presentation; D000936:Antigen-Antibody Complex / Q000276:immunology*; D002454:Cell Differentiation; D002461:Cell Line, Transformed; D003601:Cytotoxicity Tests, Immunologic; D003713:Dendritic Cells / Q000276:immunology*; D004705:Endocytosis; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000502:physiology; D006825:Hybridomas; D051379:Mice; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D010047:Ovalbumin / Q000276:immunology / Q000378:metabolism; D010455:Peptides / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D000936:Antigen-Antibody Complex; D015395:Histocompatibility Antigens Class I; D010455:Peptides; D010047:Ovalbumin