Abstract
In the course of viral infection, the immune system exploits only a fraction of the available CTL repertoire and focuses on a few of a myriad of potentially antigenic peptides. This phenomenon, known as immunodominance, depends on a number of factors, including antigen processing and transport, MHC binding, competition for antigen-presenting cells, availability of the CD8 T cell repertoire and other mechanisms that function largely by restricting the immune response. Here we elucidate a novel mechanism that increases the immunodominance of the epitope rather by enhancing the immune response. Using a peptide-specific MHC-restricted mAb and functional assays of CTL activation, we show that T cells with high avidity for the immunodominant, H-2D(d) restricted, P18-I10 epitope expand rapidly following immunization, and this expansion in turn determines the level of the P18-I10 epitope immunodominance. This proliferation has little dependence on the number of MHC-peptide complexes. Since most self-reactive T cells of high avidity are depleted in the thymus, the selection of immunodominant epitopes based on the expansion of high-avidity T cells in the periphery reduces the potential for autoimmunity.
Publication types
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Research Support, N.I.H., Intramural
MeSH terms
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Animals
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CD8-Positive T-Lymphocytes / cytology
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CD8-Positive T-Lymphocytes / immunology*
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CD8-Positive T-Lymphocytes / metabolism
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Cell Count
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Cell Line, Tumor
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Cell Proliferation
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Dendritic Cells / immunology
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Dendritic Cells / metabolism
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H-2 Antigens / immunology
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H-2 Antigens / metabolism
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HIV Envelope Protein gp120 / immunology
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HIV Envelope Protein gp120 / metabolism
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HIV Envelope Protein gp160 / genetics
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HIV Envelope Protein gp160 / immunology
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Histocompatibility Antigen H-2D
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Immunodominant Epitopes / immunology*
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Interferon-gamma / metabolism
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Lymphocyte Activation / immunology
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Major Histocompatibility Complex / genetics
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Major Histocompatibility Complex / immunology
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Mice
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Mice, Inbred BALB C
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Mice, Inbred DBA
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Mice, Inbred Strains
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Models, Immunological
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Peptide Fragments / immunology
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Peptide Fragments / metabolism
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Receptors, Antigen, T-Cell / immunology
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Spleen / cytology
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Spleen / immunology
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T-Lymphocytes, Cytotoxic / cytology
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T-Lymphocytes, Cytotoxic / immunology*
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T-Lymphocytes, Cytotoxic / metabolism
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Vaccination / methods
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Vaccinia virus / genetics
Substances
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H-2 Antigens
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HIV Envelope Protein gp120
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HIV Envelope Protein gp160
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Histocompatibility Antigen H-2D
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Immunodominant Epitopes
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P18-I10 peptide
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Peptide Fragments
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Receptors, Antigen, T-Cell
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Interferon-gamma