TLR agonists downregulate H2-O in CD8α- dendritic cells Journal Article
| Authors: | Porter, G. W.; Yi, W.; Denzin, L. K. |
| Article Title: | TLR agonists downregulate H2-O in CD8α- dendritic cells |
| Abstract: | Peptide loading of MHC class II (MHCII) molecules is catalyzed by the nonclassical MHCII-related molecule H2-M. H2-O, another MHCII-like molecule, associates with H2-M and modulates H2-M function. The MHCII presentation pathway is tightly regulated in dendritic cells (DCs), yet how the key modulators of MHCII presentation, H2-M and H2-O, are affected in different DC subsets in response to maturation is unknown. In this study, we show that H2-O is markedly downregulated in vivo in mouse CD8α- DCs in response to a broad array of TLR agonists. In contrast, CD8α+ DCs only modestly downregulated H2-O in response to TLR agonists. H2-M levels were slightly downmodulated in both CD8α- and CD8α+ DCs. As a consequence, H2-M/H2-O ratios significantly increased for CD8α - but not for CD8α+ DCs. The TLR-mediated downregulation was DC specific, as B cells did not show significant H2-O and H2-M downregulation. TLR4 signaling was required to mediate DC H2-O downregulation in response to LPS. Finally, our studies showed that the mechanism of H2-O downregulation was likely due to direct protein degradation of H2-O as well as downregulation of H2-O mRNA levels. The differential H2-O and H2-M modulation after DC maturation supports the proposed roles of CD8α- DCs in initiating CD4-restricted immune responses by optimal MHCII presentation and of CD8α+ DCs in promoting immune tolerance via presentation of low levels of MHCII-peptide. Copyright © 2011 by The American Association of Immunologists, Inc. |
| Keywords: | signal transduction; controlled study; protein expression; unclassified drug; nonhuman; protein function; animal cell; mouse; cell maturation; dendritic cell; protein degradation; cell differentiation; b lymphocyte; toll like receptor 4; immunological tolerance; antigen presentation; cellular immunity; enzyme regulation; major histocompatibility antigen class 2; hla dm antigen; hla do antigen; toll like receptor agonist; cd8alpha antigen; h2 m antigen; h2 o antigen |
| Journal Title: | Journal of Immunology |
| Volume: | 187 |
| Issue: | 8 |
| ISSN: | 0022-1767 |
| Publisher: | The American Association of Immunologists, Inc |
| Date Published: | 2011-10-15 |
| Start Page: | 4151 |
| End Page: | 4160 |
| Language: | English |
| DOI: | 10.4049/jimmunol.1003137 |
| PROVIDER: | scopus |
| PMCID: | PMC3186832 |
| PUBMED: | 21918198 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 9 December 2011" - "CODEN: JOIMA" - "Source: Scopus" |
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