Detection of CD8+ T Cells Sensitized to BK Virus Large T Antigen in Healthy Volunteers and Kidney Transplant Recipients

Abstract

BK virus (BKV) infections after renal transplantation are increasingly recognized. Development of immune monitoring strategies against BKV requires definition of antigenic epitopes. Hence, T cells from HLA-A02-positive healthy subjects and kidney transplant recipients were stimulated by BKV lysate pulsed on mature autologous dendritic cells and screened against four different T antigen peptides or against BKV lysate. IFN-γ production was measured by ELISPOT assays. The peptide BKV362–371 (MLTERFNHIL) was naturally processed and recognized by five of six healthy subjects (39 ± 11 IFN-γ spots/100,000 cells) and five of seven kidney transplant recipients (21 ± 12 IFN-γ spots). Less frequent and weaker CD8⁺ T-cell responses were detected against three other peptides. Thus, BKV large T antigen is a target for CD8⁺ T-cell immunity. T-antigen-specific T-cytotoxic cells circulate in healthy blood donors, implying that transient expression of T antigen presumably occurs at sites of viral latency and helps maintain a constant pool of circulating CD8⁺ T memory cells.