Abstract
To study the induction of anti-"self" CD8+ T-cell reactivity against the tumor antigen gp100, we used a mouse transgenic for a chimeric HLA-A*0201/H-2 Kb molecule (A2/Kb). We immunized the mice with a recombinant vaccinia virus encoding a form of gp100 that had been modified at position 210 (from a threonine to a methionine) to increase epitope binding to the restricting class I molecule. Immunogens containing the "anchor-fixed" modification elicited anti-self CD8+ T cells specific for the wild-type gp100(209-217) peptide pulsed onto target cells. More important, these cells specifically recognized the naturally presented epitope on the surface of an A2/Kb-expressing murine melanoma, B16. These data indicate that anchor-fixing epitopes could enhance the function of recombinant virus-based immunogens.
MeSH terms
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Animals
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Antigen Presentation / genetics
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Antigen Presentation / immunology
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Autoimmunity / genetics
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Autoimmunity / immunology*
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CD8-Positive T-Lymphocytes / immunology*
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Cancer Vaccines / genetics
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Cancer Vaccines / immunology*
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Epitopes / immunology
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HLA-A Antigens / genetics
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HLA-A Antigens / immunology*
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Immunity, Cellular
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Melanoma, Experimental / immunology*
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Membrane Glycoproteins / genetics
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Membrane Glycoproteins / immunology*
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Mice
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Mice, Transgenic
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Neoplasm Proteins / genetics
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Neoplasm Proteins / immunology*
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Peptide Fragments / genetics
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Peptide Fragments / immunology*
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Transfection*
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Vaccinia virus / genetics
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Vaccinia virus / immunology
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gp100 Melanoma Antigen
Substances
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Cancer Vaccines
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Epitopes
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HLA-A Antigens
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Membrane Glycoproteins
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Neoplasm Proteins
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Peptide Fragments
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Pmel protein, mouse
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gp100 Melanoma Antigen