Submitted October 8, 2008
Accepted November 2, 2008
Developmental regulation of MHC II expression and transport in human plasmacytoid-derived dendritic cells
Charlotte Sadaka, Marie-Annick Marloie-Provost, Vassili Soumelis, and Philippe Benaroch*
INSERM U653, Institut Curie, Paris, France
* Corresponding author; email: benaroch{at}curie.fr.
Plasmacytoid pre-dendritic cells (pDCs) play a key role in antiviral immunity through their capacity to produce large amounts of type I IFNs in response to Toll like receptor (TLR) triggering, and to differentiate into dendritic cells (DC). However their antigen processing and presentation pathways remain poorly characterized. In this study, we analyzed MHC II synthesis and transport in primary human pDCs. We show that stimulation of pDC with influenza virus leads to a sustained neosynthesis of MHC II molecules, which rapidly accumulate in antigen loading compartments organized around the MTOC. MHC II endocytosis as well as antigen internalization remain active during the entire process of pDC differentiation into DCs suggesting a capacity to constantly renew surface peptide-MHC II complexes. Formation of the intracellular pool of MHC II in activated pDC is NF-
B-dependent and associated with acquisition of a dendritic phenotype, but independent of the IRF7-type I IFN-dependent pathway, suggesting that innate and adaptive functions of pDCs are differentially regulated. Our data demonstrate that the regulation of MHC II expression and transport is drastically different in pDCs compared to conventional DCs, indicating distinct and potentially complementary immuno-regulatory functions.
