Enhancement of dendritic cell antigen cross-presentation by CpG DNA involves type IIFN and stabilization of class I MHC mRNA

Dendritic cells (DCs) internalize exogenous Ags and process them for cross-presentation by class I MHC (MHC-1) to CD8(+) T cells. This processing can occur by transporter for Ag presentation (TAP)-dependent or TAP-independent mechanisms. We observed that CpG DNA enhanced cross-presentation of Ags by Flt-3L-cultured bone marrow-derived murine DCs by a type I IFN (IFN-alpha beta)-dependent mechanism. Myeloid DCs provided cross-presentation function in this system. Both TAPI knockout and wild-type DCs showed enhanced cross-presentation when treated with CpG DNA at 26 degrees C, demonstrating that TAP is not essential to this regulatory mechanism, although TAP is an important determinant of MHC-I expression. Enhancement of cross-processing by CpG DNA did not involve increased Ag uptake or proteolysis but did correlate with IFN-alpha beta-dependent increases in expression of MHC-I mRNA and protein. Increased MHC-I mRNA levels resulted in part from stabilization of MHC-I mRNA, a novel posttranscriptional mechanism for regulation of MHC-I expression. Thus, a major mechanism by which CpG oligodeoxynucleotide increase cross presentation by DCs appears to be an IFN-alpha beta-mediated increase in MHC-I synthesis.