title: 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.
abstract: Human polyomavirus BK (BKV) has been implicated in oncogenic transformation. Its ability to replicate is determined by the binding of its large tumor antigen (LTag) to products of tumor-suppressor genes regulating cell cycle, as specifically p53. We investigated CD8+ T immune responses to BKV LTag portions involved in p53 binding in HLA-A*0201+ BKV LTag experienced individuals. 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-gamma 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.
authors.affiliation: Institute of Surgical Research and Hospital Management, University Hospital Basel, Switzerland. mprovenzano@uhbs.ch
authors.forename: Maurizio
authors.initials: M
authors.lastname: Provenzano
authors.forename: Laura
authors.initials: L
authors.lastname: Bracci
authors.forename: Stephen
authors.initials: S
authors.lastname: Wyler
authors.forename: Tvrtko
authors.initials: T
authors.lastname: Hudolin
authors.forename: Giovanni
authors.initials: G
authors.lastname: Sais
authors.forename: Rainer
authors.initials: R
authors.lastname: Gosert
authors.forename: Paul
authors.initials: P
authors.lastname: Zajac
authors.forename: Giorgio
authors.initials: G
authors.lastname: Palu'
authors.forename: Michael
authors.initials: M
authors.lastname: Heberer
authors.forename: Hans H
authors.initials: HH
authors.lastname: Hirsch
authors.forename: Giulio C
authors.initials: GC
authors.lastname: Spagnoli