Document Detail


Dendritic cells sequester antigenic epitopes for prolonged periods in the absence of antigen-encoding genetic information.
MedLine Citation:
PMID:  23045695     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Studies with a number of viral systems have shown, on the basis of the ability of a host to prime naïve T cells, that viral antigens persist in the infected host well beyond complete clearance of the infection and even when viral antigen is undetectable by the most sensitive methods. This has led to a reasonable assumption that the antigen persists through persistence of antigen-encoding genetic information (DNA or RNA) that resides in the host at a subdetectable level. Here, we demonstrate that epitopes, or epitope precursors, of a model antigen (ovalbumin) persist in a host for prolonged periods (weeks), well beyond the time at which the intact antigen has disappeared, and in the complete absence of genetic information encoding it. Dendritic cells are shown to be the site of this epitope sequestration in vivo, as well as in cultures in vitro. For sequestration to occur, the uptaken antigen must be significantly large, that is, the epitope and its 18-mer precursor are not sequestered. Dendritic cells are shown to create an hsp90-dependent intracellular pool of epitopes or epitope precursors that continues to release epitopes for presentation on the major histocompatibility complex I molecules for prolonged periods. Demonstration of such long-term sequestration of antigenic epitopes inside dendritic cells presents new opportunities for stimulation of immune response against cancers and viruses.
Authors:
Changying Li; Matthew R Buckwalter; Sreyashi Basu; Manish Garg; Jiwu Chang; Pramod K Srivastava
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-10-08
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  109     ISSN:  1091-6490     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-10-24     Completed Date:  2013-01-07     Revised Date:  2013-07-11    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  17543-8     Citation Subset:  IM    
Affiliation:
Center for Immunotherapy of Cancer and Infectious Diseases, Department of Immunology, University of Connecticut School of Medicine, Farmington, CT 06030, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antigens / genetics,  immunology*
Dendritic Cells / immunology*
Epitopes / immunology*
HSP90 Heat-Shock Proteins / immunology
Mice
Mice, Inbred C57BL
Grant Support
ID/Acronym/Agency:
CA084479/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Antigens; 0/Epitopes; 0/HSP90 Heat-Shock Proteins
Comments/Corrections

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