BKV and JCV large T antigen-specific CD8⁺ T cell response in HLA A*0201⁺ kidney transplant recipients with polyomavirus nephropathy and patients with progressive multifocal leukoencephalopathy

Background: BK virus (BKV), which causes polyomavirus-associated nephropathy (PVN) in kidney transplant recipients (KTx), has 75% homology with JC virus (JCV), the etiologic agent of progressive multifocal leukoencephalopathy (PML). The large T-antigen (T-ag) is the main regulatory protein of polyomaviruses that is expressed early in the viral cycle. Objectives: To characterize epitopes of BKV and JCV T-ag recognized by CD8⁺ T-cells and explore the role of these cells in containing polyomavirus infection. Study design: We tested peripheral blood mononuclear cells of HLA A*0201⁺ BKV- and JCV-seropositive individuals, including patients with active BKV or JCV infection and healthy control subjects in a cross-sectional study. Results: CD8⁺ T-cells that recognized the nonamer BKV T_p579, which is identical to JCV T_p578, were detected by tetramer staining in 10/13 (77%) healthy individuals, 3/10 (30%) KTx/PVN, and 4/9 (44%) patients with PML and/or HIV-infection. Conversely, BKV T_p398- and T_p410-specific CD8⁺ T cells were detected in 3/13 (23%) and 1/13 (8%) healthy individuals only. Conclusion: These data suggest that, as it is the case for the VP1 protein, the same population of CD8⁺ T-cells may recognize epitopes located on the BKV and JCV T protein. The overall cellular immune response against polyomavirus T-ag, however, is lower than against the VP1 protein and is more frequently detected in healthy individuals than in patients with active BKV or JCV infection.