Abstract
Polyomavirus BK (BKV) infections are increasingly recognized. The development of immune-monitoring strategies against BKV requires definition of antigenic epitopes. Bioinformatic algorithms were used to identify 60 BKV large T-antigen (LT-Ag) peptides predicted to bind HLA class I alleles. In vitro peptide binding was used to select a subset of 19 peptides for interferon (IFN)-gamma ELISPOT assays in 13 healthy subjects and 12 kidney transplant recipients. Four A01-, nine A03-, and five A24-binding immunogenic peptides were identified in 1 to 3 (14-67%) tested subjects in each group. BKV epitope sequences were identical to homologous JC virus sequences for 3 of 19 peptides and homologous SV40 sequences for 5 of 19 peptides. Homology modeling localized these epitopes to the helicase, origin of DNA binding, or J domains, respectively. In conclusion, we have identified multiple 9-mer BKV LT-Ag-derived immunogenic epitopes that bind HLA-A01, -A03, or -A24 molecules. Sequence alignments indicate that two epitopes, FLICKGVNK and RYWLFKGPI, are common to BKV, JC virus, and SV40 virus.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Adult
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Antigens, Viral, Tumor / genetics
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Antigens, Viral, Tumor / immunology
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Antigens, Viral, Tumor / metabolism*
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BK Virus / genetics
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BK Virus / immunology*
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BK Virus / pathogenicity
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Cells, Cultured
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Computer Simulation
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Epitope Mapping
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Epitopes, T-Lymphocyte / genetics
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Epitopes, T-Lymphocyte / immunology
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Epitopes, T-Lymphocyte / metabolism*
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Female
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Graft Rejection / complications
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Graft Rejection / immunology*
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Graft Rejection / pathology
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Graft Rejection / virology
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HLA-A Antigens / metabolism*
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Humans
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Interferon-gamma / metabolism
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JC Virus / genetics
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JC Virus / immunology
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Kidney Transplantation
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Lymphocyte Activation
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Male
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Middle Aged
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Peptide Fragments / genetics
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Peptide Fragments / immunology
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Peptide Fragments / metabolism*
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Polyomavirus Infections / complications
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Polyomavirus Infections / immunology*
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Polyomavirus Infections / pathology
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Polyomavirus Infections / virology
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Protein Binding
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Sequence Alignment
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Simian virus 40 / genetics
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Simian virus 40 / immunology
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T-Lymphocytes / immunology
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T-Lymphocytes / metabolism
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T-Lymphocytes / pathology
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Tumor Virus Infections / complications
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Tumor Virus Infections / immunology*
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Tumor Virus Infections / pathology
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Tumor Virus Infections / virology
Substances
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Antigens, Viral, Tumor
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Epitopes, T-Lymphocyte
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HLA-A Antigens
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Peptide Fragments
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Interferon-gamma