Type I IFN drives a distinctive dendritic cell maturation phenotype that allows continued MHC-II synthesis and antigen processing (106.21)

Abstract

Abstract Microbial molecules or cytokines can stimulate dendritic cell (DC) maturation, which involves DC migration to lymph nodes and enhanced presentation of Ag to launch T cell responses. Toll-like receptor (TLR) agonists are the most studied inducers of DC maturation and promote a burst of Ag processing with enhanced expression of peptide-MHC-II complexes and co-stimulatory molecules. Subsequently, MHC-II localization is shifted from vacuolar compartments to the surface and synthesis is inhibited, thus decreasing Ag processing and limiting presentation to a cohort of Ags kinetically associated with the maturation signal. Type I interferon (IFN-I) also promotes DC maturation, but the phenotypic changes induced by IFN-I are poorly defined. Our studies show that treatment of DC with IFN-I also increases MHC-II Ag presentation, but, in contrast to TLR-induced maturation, allows for continued Ag processing. IFN-I treated DC expressed high levels of MHC-II at the surface as well as in vacuolar compartments, consistent with sustained Ag processing function. Expression of mRNA for MHC-II and CIITA was inhibited in DC treated with TLR agonists, but maintained in DC matured with IFN-I. Similar to TLR agonists, however, IFN-I induced changes in MARCH1 expression and MHC-II ubiquitination. Our findings suggest that IFN-I drives a distinctive DC maturation program that enhances Ag presentation to T cells without a shutdown of Ag processing, allowing continued sampling of Ags for presentation.