Interplay of cellular and humoral immune responses against BK virus in kidney transplant recipients with polyomavirus nephropathy.

Details

Serval ID
serval:BIB_A58C836C8B00
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Interplay of cellular and humoral immune responses against BK virus in kidney transplant recipients with polyomavirus nephropathy.
Journal
Journal of Virology
Author(s)
Chen Y., Trofe J., Gordon J., Du Pasquier R.A., Roy-Chaudhury P., Kuroda M.J., Woodle E.S., Khalili K., Koralnik I.J.
ISSN
0022-538X[print], 0022-538X[linking]
Publication state
Published
Issued date
2006
Peer-reviewed
Oui
Volume
80
Number
7
Pages
3495-3505
Language
english
Notes
Publication types: Comparative Study ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
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.
Keywords
Adult, Aged, Antibody Formation/immunology, BK Virus/immunology, Capsid Proteins/genetics, Capsid Proteins/immunology, Epitopes, HLA-A Antigens/genetics, HLA-A Antigens/metabolism, Humans, Immunity, Cellular/immunology, In Situ Hybridization, Kidney Diseases/metabolism, Kidney Diseases/virology, Kidney Transplantation, Kinetics, Middle Aged, Polyomavirus/immunology, Polyomavirus Infections/immunology, T-Lymphocytes, Cytotoxic/immunology, Transplantation, Homologous, Viral Load
Pubmed
Web of science
Open Access
Yes
Create date
25/01/2008 14:56
Last modification date
20/08/2019 15:10
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