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

Kuchtey J, Chefalo PJ, Gray RC, Ramachandra L, Harding CV
J Immunol. 2005 175 (4): 2244-51

PMID: 16081792 · DOI:10.4049/jimmunol.175.4.2244

Dendritic cells (DCs) internalize exogenous Ags and process them for cross-presentation by class I MHC (MHC-I) 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-alphabeta)-dependent mechanism. Myeloid DCs provided cross-presentation function in this system. Both TAP1 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-alphabeta-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-alphabeta-mediated increase in MHC-I synthesis.

MeSH Terms (21)

Adjuvants, Immunologic Animals ATP-Binding Cassette Transporters ATP Binding Cassette Transporter, Subfamily B, Member 2 Cells, Cultured CpG Islands Cross-Priming Dendritic Cells Half-Life Histocompatibility Antigens Class I Interferon-alpha Interferon-beta Mice Mice, Inbred C57BL Mice, Knockout Oligodeoxyribonucleotides Ovalbumin RNA, Messenger RNA Stability Signal Transduction Up-Regulation

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