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rdf:type |
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lifeskim:mentions |
umls-concept:C0003451,
umls-concept:C0035647,
umls-concept:C0039194,
umls-concept:C0042210,
umls-concept:C0079600,
umls-concept:C0085358,
umls-concept:C0205263,
umls-concept:C0221102,
umls-concept:C1332717,
umls-concept:C1413244,
umls-concept:C1706438,
umls-concept:C2698600
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pubmed:issue |
1
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pubmed:dateCreated |
2009-6-22
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pubmed:abstractText |
Immunodominance limits the TCR diversity of specific antiviral CD8 T cell responses elicited by vaccination or infection. To prime multispecific T cell responses, we constructed DNA vaccines that coexpress chimeric, multidomain Ags (with CD8 T cell-defined epitopes of the hepatitis B virus (HBV) surface (S), core (C), and polymerase (Pol) proteins and/or the OVA Ag as stress protein-capturing fusion proteins. Priming of mono- or multispecific, HLA-A*0201- or K(b)-restricted CD8 T cell responses by these DNA vaccines differed. K(b)/OVA(257-264)- and K(b)/S(190-197)-specific CD8 T cell responses did not allow priming of a K(b)/C(93-100)-specific CD8 T cell response in mice immunized with multidomain vaccines. Tolerance to the S- Ag in transgenic Alb/HBs mice (that express large amounts of transgene-encoded S- Ag in the liver) facilitated priming of subdominant, K(b)/C(93-100)-specific CD8 T cell immunity by multidomain Ags. The "weak" (i.e., easily suppressed) K(b)/C(93-100)-specific CD8 T cell response was efficiently elicited by a HBV core Ag-encoding vector in 1.4HBV-S(mut) tg mice (that harbor a replicating HBV genome that produces HBV surface, core, and precore Ag in the liver). K(b)/C(93-100)-specific CD8 T cells accumulated in the liver of vaccinated 1.4HBV-S(mut) transgenic mice where they suppressed HBV replication. Subdominant epitopes in vaccines can hence prime specific CD8 T cell immunity in a tolerogenic milieu that delivers specific antiviral effects to HBV-expressing hepatocytes.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
AIM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, Polyomavirus Transforming,
http://linkedlifedata.com/resource/pubmed/chemical/Epitopes, T-Lymphocyte,
http://linkedlifedata.com/resource/pubmed/chemical/H-2 Antigens,
http://linkedlifedata.com/resource/pubmed/chemical/H-2Kb protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/HSP70 Heat-Shock Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Hepatitis B Core Antigens,
http://linkedlifedata.com/resource/pubmed/chemical/Hepatitis B Vaccines,
http://linkedlifedata.com/resource/pubmed/chemical/Hepatitis B e Antigens,
http://linkedlifedata.com/resource/pubmed/chemical/Immunodominant Epitopes,
http://linkedlifedata.com/resource/pubmed/chemical/Vaccines, DNA
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
1550-6606
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:day |
1
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pubmed:volume |
183
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
370-80
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pubmed:meshHeading |
pubmed-meshheading:19542448-Animals,
pubmed-meshheading:19542448-Antigens, Polyomavirus Transforming,
pubmed-meshheading:19542448-CD8-Positive T-Lymphocytes,
pubmed-meshheading:19542448-Cell Line,
pubmed-meshheading:19542448-Epitopes, T-Lymphocyte,
pubmed-meshheading:19542448-Female,
pubmed-meshheading:19542448-H-2 Antigens,
pubmed-meshheading:19542448-HSP70 Heat-Shock Proteins,
pubmed-meshheading:19542448-Hepatitis B Core Antigens,
pubmed-meshheading:19542448-Hepatitis B Vaccines,
pubmed-meshheading:19542448-Hepatitis B e Antigens,
pubmed-meshheading:19542448-Hepatitis B virus,
pubmed-meshheading:19542448-Humans,
pubmed-meshheading:19542448-Immunodominant Epitopes,
pubmed-meshheading:19542448-Liver Diseases,
pubmed-meshheading:19542448-Lymphocyte Activation,
pubmed-meshheading:19542448-Male,
pubmed-meshheading:19542448-Mice,
pubmed-meshheading:19542448-Mice, Inbred C57BL,
pubmed-meshheading:19542448-Mice, Transgenic,
pubmed-meshheading:19542448-Protein Binding,
pubmed-meshheading:19542448-Protein Structure, Tertiary,
pubmed-meshheading:19542448-Vaccines, DNA,
pubmed-meshheading:19542448-Virus Replication
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pubmed:year |
2009
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pubmed:articleTitle |
Elimination of immunodominant epitopes from multispecific DNA-based vaccines allows induction of CD8 T cells that have a striking antiviral potential.
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pubmed:affiliation |
Department of Internal Medicine I, University of Ulm, Germany.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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