HLA-A01-, -A03-, and -A024-binding nanomeric epitopes in polyomavirus BK large T antigen.
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.
Ramaswami
Bala
B
Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.
Popescu
Iulia
I
Macedo
Camila
C
Metes
Diana
D
Bueno
Marta
M
Zeevi
Adriana
A
Shapiro
Ron
R
Viscidi
Raphael
R
Randhawa
Parmjeet S
PS
D000328:Adult; D000957:Antigens, Viral, Tumor / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D001739:BK Virus / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity; D002478:Cells, Cultured; D003198:Computer Simulation; D018604:Epitope Mapping; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D005260:Female; D006084:Graft Rejection / Q000150:complications / Q000276:immunology* / Q000473:pathology / Q000821:virology; D015234:HLA-A Antigens / Q000378:metabolism*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D007577:JC Virus / Q000235:genetics / Q000276:immunology; D016030:Kidney Transplantation; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D027601:Polyomavirus Infections / Q000150:complications / Q000276:immunology* / Q000473:pathology / Q000821:virology; D011485:Protein Binding; D016415:Sequence Alignment; D013539:Simian virus 40 / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D014412:Tumor Virus Infections / Q000150:complications / Q000276:immunology* / Q000473:pathology / Q000821:virology
D000957:Antigens, Viral, Tumor; D018984:Epitopes, T-Lymphocyte; D015234:HLA-A Antigens; D010446:Peptide Fragments; D007371:Interferon-gamma