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.


OBJECTIVE
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.


METHODS
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 Tp579, which is identical to JCV Tp578, 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 Tp398- and Tp410-specific CD8+ T cells were detected in 3/13 (23%) and 1/13 (8%) healthy individuals only.


CONCLUSIONS
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.
Chen
Yiping
Y
Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
Trofe
Jennifer
J
Gordon
Jennifer
J
Autissier
Patrick
P
Woodle
E Steve
ES
Koralnik
Igor J
IJ
D000595:Amino Acid Sequence; D000957:Antigens, Viral, Tumor / Q000737:chemistry / Q000276:immunology*; D001739:BK Virus / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003429:Cross Reactions; D003601:Cytotoxicity Tests, Immunologic; D000939:Epitopes / Q000737:chemistry / Q000276:immunology; D015234:HLA-A Antigens / Q000737:chemistry / Q000378:metabolism; D015789:HLA-A2 Antigen; D006801:Humans; D007577:JC Virus / Q000276:immunology*; D007674:Kidney Diseases / Q000276:immunology / Q000821:virology; D016030:Kidney Transplantation; D007968:Leukoencephalopathy, Progressive Multifocal / Q000276:immunology / Q000821:virology; D008969:Molecular Sequence Data; D027601:Polyomavirus Infections / Q000276:immunology / Q000821:virology
D000957:Antigens, Viral, Tumor; D000939:Epitopes; D015234:HLA-A Antigens; C435939:HLA-A*02:01 antigen; D015789:HLA-A2 Antigen