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Provenzano, Maurizio and Bracci, Laura and Wyler, Stephen and Hudolin, Tvrtko and Sais, Giovanni and Gosert, Rainer and Zajac, Paul and Palu, Giorgio and Heberer, Michael and Hirsch, Hans H and Spagnoli, Giulio C (2006) 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. [Online journal papers]

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Abstract (english)

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-? 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.

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EPrint type:Online journal papers
Anno di Pubblicazione:2006
Key Words:human polyomavirus, oncogenic transformation
Settori scientifico-disciplinari MIUR:Area 06 - Scienze mediche > MED/06 Oncologia medica
Struttura di riferimento:Dipartimenti > pre 2012 Dipartimento di Istologia, Microbiologia e Biotecnologie Mediche
Codice ID:1253
Depositato il:09 Dec 2008
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