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TLR Agonists Downregulate H2-O in CD8{alpha}- Dendritic Cells.
MedLine Citation:
PMID:  21918198     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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.
Authors:
Gavin W Porter; Woelsung Yi; Lisa K Denzin
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-9-14
Journal Detail:
Title:  Journal of immunology (Baltimore, Md. : 1950)     Volume:  -     ISSN:  1550-6606     ISO Abbreviation:  -     Publication Date:  2011 Sep 
Date Detail:
Created Date:  2011-9-15     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  2985117R     Medline TA:  J Immunol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Immunology Program, Sloan-Kettering Institute, Memorial Sloan-Kettering Cancer Center, New York, NY 10065;
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