Document Detail


The murine B cell repertoire is severely selected against endogenous cellular prion protein.
MedLine Citation:
PMID:  16272297     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Abs to the prion protein (PrP) can protect against experimental prion infections, but efficient Ab responses are difficult to generate because PrP is expressed on many tissues and induces a strong tolerance. We previously showed that immunization of wild-type mice with PrP peptides and CpG oligodeoxynucleic acid overcomes tolerance and induces cellular and humoral responses to PrP. In this study, we compared Ab and T cell repertoires directed to PrP in wild-type and PrP knockout (Prnp o/o) C57BL/6 mice. Animals were immunized with mouse PrP-plasmid DNA or with 30-mer overlapping peptides either emulsified in CFA or CpG/IFA. In Prnp o/o mice, Abs raised by PrP-plasmid DNA immunization recognized only N-terminal PrP peptides; analyses of Ab responses after PrP peptide/CFA immunization allowed us to identify six distinct epitopes, five of which were also recognized by Abs raised by PrP peptides/CpG. By contrast, in wild-type mice, no Ab response was detected after PrP-plasmid DNA or peptide/CFA immunization. However, when using CpG, four C-terminal peptides induced Abs specific for distinct epitopes. Importantly, immune sera from Prnp o/o but not from wild-type mice bound cell surface PrP. Abs of IgG1 and IgG2b subclasses predominated in Prnp o/o mice while the strongest signals were for IgG2b in wild-type mice. Most anti-PrP Th cells were directed to a single epitope in both Prnp o/o and wild-type mice. We conclude that endogenous PrPC expression profoundly affects the Ab repertoire as B cells reactive for epitopes exposed on native PrPC are strongly tolerized. Implications for immunotherapy against prion diseases are discussed.
Authors:
Sylvie Grégoire; Anne Sophie Bergot; Cécile Féraudet; Claude Carnaud; Pierre Aucouturier; Martine Bruley Rosset
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of immunology (Baltimore, Md. : 1950)     Volume:  175     ISSN:  0022-1767     ISO Abbreviation:  J. Immunol.     Publication Date:  2005 Nov 
Date Detail:
Created Date:  2005-11-07     Completed Date:  2006-01-03     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  2985117R     Medline TA:  J Immunol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  6443-9     Citation Subset:  AIM; IM    
Affiliation:
Institut National de la Santé et de la Recherche Médicale Unité 712 and Université Pierre et Marie Curie, Hôpital Saint-Antoine, Paris, France.
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MeSH Terms
Descriptor/Qualifier:
Amino Acid Sequence
Animals
Autoantibodies / biosynthesis
B-Lymphocytes / immunology*
Epitope Mapping
Epitopes / genetics
Female
Immune Tolerance
Immunization
Immunoglobulin G / biosynthesis
Immunotherapy
Mice
Mice, Inbred C57BL
Mice, Knockout
Molecular Sequence Data
Prion Diseases / immunology,  therapy
Prions / genetics,  immunology*
T-Lymphocytes / immunology
Chemical
Reg. No./Substance:
0/Autoantibodies; 0/Epitopes; 0/Immunoglobulin G; 0/Prions

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