Document Detail


Fusion proteins for versatile antigen targeting to cell surface receptors reveal differential capacity to prime immune responses.
MedLine Citation:
PMID:  20483719     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Targeting of proteins to APCs is an attractive strategy for eliciting adaptive immune responses. However, the relationship between the choice of the targeted receptor and the quality and quantity of responses remains poorly understood. We describe a strategy for expression of Ags including hydrophobic proteins as soluble fusion proteins that are optimized for proteasome-dependent MHC class I-restricted cross-presentation and form stable complexes with a wide variety of targeting Abs. Upon s.c. immunization, these complexes were initially taken up by CD169+ lymph node subcapsular sinus macrophages. In the OVA model system, receptor-targeted antigenic complexes primed specific T and B cell responses in vitro and in vivo at least 100-fold more efficiently than Ag alone. Comparison of 10 targeting receptors allowed us to establish a ranking with respect to priming of CD8+ T cell responses and demonstrated striking differences with respect to the relative efficacy of CD8+ and CD4+ T cell subset and B cell priming. The described fusion proteins should help in developing optimized strategies for targeted delivery of protein Ags in the context of tolerization or vaccination.
Authors:
Roland Kratzer; Fran?ois-Xavier Mauvais; Anne Burgevin; Emilie Barilleau; Peter van Endert
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-05-14
Journal Detail:
Title:  Journal of immunology (Baltimore, Md. : 1950)     Volume:  184     ISSN:  1550-6606     ISO Abbreviation:  J. Immunol.     Publication Date:  2010 Jun 
Date Detail:
Created Date:  2010-06-07     Completed Date:  2010-06-18     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  2985117R     Medline TA:  J Immunol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  6855-64     Citation Subset:  AIM; IM    
Affiliation:
Institut National de la Sant? et de la Recherch? M?dicale, Unit? 1013, Paris, France.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antigen Presentation / immunology*
Antigens / immunology*
B-Lymphocytes / immunology
Blotting, Western
Cross-Priming / immunology*
Humans
Mice
Mice, Inbred C57BL
Recombinant Fusion Proteins / immunology*
T-Lymphocytes / immunology
Chemical
Reg. No./Substance:
0/Antigens; 0/Recombinant Fusion Proteins

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


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