| The murine B cell repertoire is severely selected against endogenous cellular prion protein. | |
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MedLine Citation:
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PMID: 16272297 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Sylvie Grégoire; Anne Sophie Bergot; Cécile Féraudet; Claude Carnaud; Pierre Aucouturier; Martine Bruley Rosset |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Journal of immunology (Baltimore, Md. : 1950) Volume: 175 ISSN: 0022-1767 ISO Abbreviation: J. Immunol. Publication Date: 2005 Nov |
Date Detail:
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Created Date: 2005-11-07 Completed Date: 2006-01-03 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 2985117R Medline TA: J Immunol Country: United States |
Other Details:
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Languages: eng Pagination: 6443-9 Citation Subset: AIM; IM |
Affiliation:
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Institut National de la Santé et de la Recherche Médicale Unité 712 and Université Pierre et Marie Curie, Hôpital Saint-Antoine, Paris, France. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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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:
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0/Autoantibodies; 0/Epitopes; 0/Immunoglobulin G; 0/Prions |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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