Characterization of highly frequent epitope-specific CD45RA+/CCR7+/- T lymphocyte responses against p53-binding domains of the human polyomavirus BK large tumor antigen in HLA-A*0201+ BKV-seropositive donors

Peptides selected from either p53-binding region (LTag351–450 and LTag533–626) by current algorithms and capacity to bind HLA-A*0201 molecule were used to stimulate CD8+ T responses, as assessed by IFN-γ gene expression ex vivo and detected by cytotoxicity assays following in vitro culture.We observed epitope-specific immune responses in all HLA-A*0201+ BKV LTag experienced individuals tested. At least one epitope, LTag579–587; LLLIWFRPV, was naturally processed in non professional antigen presenting cells and induced cytotoxic responses with CTL precursor frequencies in the order of 1/20'000. Antigen specific CD8+ T cells were only detectable in the CD45RA+ subset, in both CCR7+ and CCR7- subpopulations.These data indicate that widespread cellular immune responses against epitopes within BKV LTag-p53 binding regions exist and question their roles in immunosurveillance against tumors possibly associated with BKV infection.Human polyomavirus BK (BKV) is a DNA virus belonging to the Polyomaviridae family that also includes human polyomavirus JC (JCV), and Simian virus 40 (SV40) (International Committee on the Taxonomy of Viruses (ICVD))[1]. The virus is ubiquitous in the human population, establishing latent infections in the kidney and the urogenital tract[2]. Spontaneous reactivation and low-level replication with shedding into urines is observed in 5–20% of healthy individuals[3]. Serological evidence indicates that nearly 90% of individuals are infected by early childhood, although a decrease in this rate during the human lifespan may be due to viral seroconversion (70–80%) [4,5]. Usually, polyomaviruses cause persistent subclinical infections in humans and BKV infection rarely leads to clinical manifestations. However, when the immune system is compromised, as following transplantation, HIV infection, chemotherapy or pharmacologic immunosuppression, rate and level of BKV replication increase and may lead to organ diseases[6]. The polyomavirus genome consists of t