Interplay of cellular and humoral immune responses against BK virus in kidney transplant recipients with polyomavirus nephropathy.
Reactivation of the polyomavirus BK (BKV) causes polyomavirus nephropathy (PVN) in kidney transplant (KTx) recipients and may lead to loss of the renal allograft. We have identified two HLA-A*0201-restricted nine-amino-acid cytotoxic T lymphocyte (CTL) epitopes of the BKV major capsid protein VP1, VP1(p44), and VP1(p108). Using tetramer staining assays, we showed that these epitopes were recognized by CTLs in 8 of 10 (VP1(p44)) and 5 of 10 (VP1(p108)) HLA-A*0201+ healthy individuals, while both epitopes elicited a CTL response in 10 of 10 KTx recipients with biopsy-proven PVN, although at variable levels. After in vitro stimulation with the respective peptides, CTLs directed against VP1(p44) were more abundant than against VP1(p108) in most healthy individuals, while the converse was true in KTx recipients with PVN, suggesting a shift in epitope immunodominance in the setting of active BKV infection. A strong CTL response in KTx recipients with PVN appeared to be associated with decreased BK viral load in blood and urine and low anti-BKV antibody titers, while a low or undetectable CTL response correlated with viral persistence and high anti-BKV antibody titers. These results suggest that this cellular immune response is present in most BKV-seropositive healthy individuals and plays an important role in the containment of BKV in KTx recipients with PVN. Interestingly, the BKV CTL epitopes bear striking homology with the recently described CTL epitopes of the other human polyomavirus JC (JCV), JCV VP1(p36) and VP1(p100). A high degree of epitope cross-recognition was present between BKV and corresponding JCV-specific CTLs, which indicates that the same population of cells is functionally effective against these two closely related viruses.
Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
Yiping
Y
Chen
Jennifer
J
Trofe
Jennifer
J
Gordon
Renaud A
RA
Du Pasquier
Prabir
P
Roy-Chaudhury
Marcelo J
MJ
Kuroda
E Steve
ES
Woodle
Kamel
K
Khalili
Igor J
IJ
Koralnik
D000328:Adult; D000368:Aged; D000917:Antibody Formation / Q000276:immunology*; D001739:BK Virus / Q000276:immunology*; D036022:Capsid Proteins / Q000235:genetics / Q000276:immunology; D000939:Epitopes; D015234:HLA-A Antigens / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology*; D017403:In Situ Hybridization; D007674:Kidney Diseases / Q000378:metabolism / Q000821:virology*; D016030:Kidney Transplantation; D007700:Kinetics; D008875:Middle Aged; D011120:Polyomavirus / Q000276:immunology*; D027601:Polyomavirus Infections / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014184:Transplantation, Homologous; D019562:Viral Load
D036022:Capsid Proteins; D000939:Epitopes; D015234:HLA-A Antigens