Impaired BK virus (BKV)-specific immunity is a key risk factor of polyomavirus-associated nephropathy. We hypothesized that
BKV agnoprotein might constitute an important immune target, as it is highly expressed after
infection in vitro. We demonstrate abundant expression of
BKV agnoprotein in vivo by immunostaining of kidney transplant (KT) biopsy specimens. Antibody responses to the recombinant affinity-purified
BKV agnoprotein, large
tumor (LT), and VP1
antigens in 146 sera from 38 KT patients and in 19 sera from 16 healthy donors (HD) were compared by
enzyme immunoassay. In HD, low titers of anti-agnoprotein
immunoglobulin G (
IgG) were found in 15% of sera, compared to 41% for anti-LT
antigen and 63% for anti-VP1. No anti-BKV
IgM was detectable. In KT patients, anti-agnoprotein
IgG and
IgM were found in 8% and 3.6% of sera, compared to 63% and 18% for anti-LT
IgG and
IgM and 80% and 41% for anti-VP1
IgG and
IgM, respectively. Anti-LT
antigen and anti-VP1, but not anti-agnoprotein, activities increased during and after BKV
viremia in KT patients. To investigate specific cellular immune responses, we compared levels of
gamma interferon production in peripheral blood mononuclear cells (PBMC) of 10 HD and 30 KT patients by
enzyme-linked immunospot assay. In HD, the median numbers of
gamma interferon spot-forming units per million PBMC for the agnoprotein, LT
antigen, and VP1
peptides were 1, 23, and 25, respectively, whereas the responses in KT patients were 2, 24, and 99, respectively. We conclude that
BKV agnoprotein, though abundantly expressed in vivo, is poorly recognized immunologically.