Document Detail


Differential MyD88/IRAK4 requirements for cross-priming and tumor rejection induced by heat shock protein 70-model antigen fusion protein.
MedLine Citation:
PMID:  22320267     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Priming of CD8(+) T cells requires two signals, one produced by T-cell receptor recognition of antigen, and a second that is often provided by the innate immune response. In this context, antigens non-covalently or covalently associated with heat shock proteins (HSP) are internalized and processed in antigen-presenting cells (APC) to be presented by MHC I molecules to CD8(+) T cells, thus, signal 1 has been well characterized in this pathway of cross-presentation. Signal 2 is not fully understood, although there are reports that Toll-like receptors (TLRs) interact with HSP and activate APC. The ability of HSP to activate APC through TLRs is, however, controversial because of the possibility of endotoxin contamination. Using a variety of TLR KO mice, we present evidence that TLRs (TLR2, 3, 4, 7, and 9) and their adaptor molecules MyD88 and IRAK4 are dispensable in cross-priming by a mycobacterial HSP70-antigen (ovalbumin as a model antigen) fusion protein; in contrast, MyD88/IRAK4, but not TLRs, are required for tumor rejection induced by the same reagent. Our results indicate that HSP-mediated cross-priming uses a second signal produced by mechanisms other than TLR cascades. We hypothesize that efficient cross-priming by HSP70 alone is insufficient for tumor rejection and that MyD88/IRAK4-dependent inflammatory stimulation, which might contribute to maintenance of the initially primed effector cells, is required to eradicate tumor burden.
Authors:
Shusaku Mizukami; Chiaki Kajiwara; Masato Tanaka; Tsuneyasu Kaisho; Heiichiro Udono
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-03-14
Journal Detail:
Title:  Cancer science     Volume:  103     ISSN:  1349-7006     ISO Abbreviation:  Cancer Sci.     Publication Date:  2012 May 
Date Detail:
Created Date:  2012-04-25     Completed Date:  2012-06-18     Revised Date:  2012-06-27    
Medline Journal Info:
Nlm Unique ID:  101168776     Medline TA:  Cancer Sci     Country:  England    
Other Details:
Languages:  eng     Pagination:  851-9     Citation Subset:  IM    
Copyright Information:
© 2012 Japanese Cancer Association.
Affiliation:
Department of Immunology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antigen-Presenting Cells / immunology
CD8-Positive T-Lymphocytes / immunology
Cross-Priming / immunology
HSP70 Heat-Shock Proteins / immunology*
Interleukin-1 Receptor-Associated Kinases / physiology*
Mice
Mice, Inbred C57BL
Mice, Knockout
Myeloid Differentiation Factor 88 / physiology*
Neoplasms / immunology*
Ovalbumin / immunology*
Recombinant Proteins / immunology
Toll-Like Receptors / immunology
Chemical
Reg. No./Substance:
0/HSP70 Heat-Shock Proteins; 0/Myd88 protein, mouse; 0/Myeloid Differentiation Factor 88; 0/Recombinant Proteins; 0/Toll-Like Receptors; 9006-59-1/Ovalbumin; EC 2.7.11.1/Interleukin-1 Receptor-Associated Kinases; EC 2.7.11.1/Irak4 protein, mouse

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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