Abstract
Peptide loading of MHC class I molecules involves multiple cofactors including tapasin. We showed previously in vitro that tapasin edits the peptide repertoire by favoring the binding of peptides with slow dissociation rates. Here, using tapasin-deficient mice and a DNA vaccine that primes directly, we confirm that tapasin establishes hierarchical responses in vivo according to peptide-MHC stability. In contrast, this hierarchy is lost when the peptides are cross-presented via an alternative DNA vaccine. By regulating transgene expression, we found that the dominant response modifier was antigen persistence. Our findings reveal strategies for activating T cells against low-affinity peptides, of potential importance for patients with repertoires narrowed by deletional tolerance.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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CD8-Positive T-Lymphocytes / immunology*
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CD8-Positive T-Lymphocytes / metabolism*
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Cross-Priming / immunology
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Egg Proteins / immunology
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Egg Proteins / pharmacokinetics*
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Histocompatibility Antigens Class I / immunology
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Histocompatibility Antigens Class I / metabolism*
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Humans
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Immunodominant Epitopes / immunology
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Immunodominant Epitopes / metabolism*
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Membrane Transport Proteins / deficiency
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Membrane Transport Proteins / genetics
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Membrane Transport Proteins / pharmacokinetics
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Membrane Transport Proteins / physiology*
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Ovalbumin / immunology
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Ovalbumin / pharmacokinetics*
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Peptide Fragments
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Signal Transduction / immunology
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Vaccines, DNA / administration & dosage
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Vaccines, DNA / immunology
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Vaccines, DNA / pharmacokinetics
Substances
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Egg Proteins
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Histocompatibility Antigens Class I
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Immunodominant Epitopes
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Membrane Transport Proteins
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OVA-8
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Peptide Fragments
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Vaccines, DNA
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tapasin
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Ovalbumin