Cited by 66Immunotherapy and Immune ResponsesImmune Response and InflammationT-cell and B-cell Immunology

Enhancement of Dendritic Cell Antigen Cross-Presentation by CpG DNA Involves Type I IFN and Stabilization of Class I MHC mRNA

Kuchtey, John, Chefalo, Peter J, Gray, Reginald C, Ramachandra, Lakshmi, Harding, Clifford V·2005·The Journal of Immunology

Abstract

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-αβ)-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°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-αβ-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-αβ-mediated increase in MHC-I synthesis.

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Crossref · 10.4049/jimmunol.175.4.2244

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Authors
Kuchtey, J., Chefalo, P. J., Gray, R. C., Ramachandra, L., & Harding, C. V.
Affiliations
Case Western Reserve University (US)
Venue
The Journal of Immunology
Published
2005-08
Volume
175
Issue
4
Pages
2244-2251
ISSN
  • 0022-1767 (ISSN-L)
  • 1550-6606
OpenAlex
W1631812628
Cited by
66
References
41
Citations by year
2025: 3 · 2024: 2 · 2023: 2 · 2022: 3 · 2021: 4 · 2020: 3 · 2019: 2 · 2018: 2 · 2017: 2 · 2015: 1 · 2014: 4 · 2013: 3 · 2012: 2
FWCI
2.60
Type
journal article
Language
en
Open access
closed
Locations
  • The Journal of Immunology (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Cancer Institute (P-30 CA43703, P30CA043703)
  • National Institute of Allergy and Infectious Diseases (R01AI034343, AI-34343, AI36219, AI47255, R01AI047255, AI055793, P30AI036219)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
  • Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
Keywords
dendritic cells, cross-presentation, CpG DNA, type I interferon, MHC class I, post-transcriptional regulation, TAP, myeloid dendritic cells, CD8+ T cells, Flt3L, bone marrow-derived dendritic cells
MeSH terms
ATP Binding Cassette Transporter, Subfamily B, Member 2, Adjuvants, Immunologic, Animals, Cells, Cultured, Dendritic Cells, Half-Life, Mice, Inbred C57BL, Oligodeoxyribonucleotides, Ovalbumin, RNA, Messenger, Histocompatibility Antigens Class I, Signal Transduction, Up-Regulation, Interferon-alpha, Interferon-beta, Mice, Knockout, ATP-Binding Cassette Transporters, CpG Islands, RNA Stability, Cross-Priming, Mice

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