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Open Access 01-06-2006 | Research

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

Authors: Maurizio Provenzano, Laura Bracci, Stephen Wyler, Tvrtko Hudolin, Giovanni Sais, Rainer Gosert, Paul Zajac, Giorgio Palu', Michael Heberer, Hans H Hirsch, Giulio C Spagnoli

Published in: Journal of Translational Medicine | Issue 1/2006

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 (LTag_351–450 and LTag_533–626) 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, LTag_579–587; 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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The Universal Virus Database of the International Committee on Taxonomy of Viruses [ http://phene.cpmc.columbia.edu ].

Hirsch HH, Steiger J: Polyomavirus BK. Lancet Infect Dis. 2003, 3 (10): 611-623. 10.1016/S1473-3099(03)00770-9.CrossRefPubMed

Hirsch HH: BK virus: opportunity makes a pathogen. Clin Infect Dis. 2005, 41 (3): 354-360. 10.1086/431488.CrossRefPubMed

Butel JS, Lednicky JA: Cell and molecular biology of simian virus 40: implications for human infections and disease. J Natl Cancer Inst. 1999, 91 (2): 119-134. 10.1093/jnci/91.2.119.CrossRefPubMed

Shah KV, Galloway DA, Knowles WA, Viscidi RP: Simian virus 40 (SV40) and human cancer: a review of the serological data. Rev Med Virol. 2004, 14 (4): 231-239. 10.1002/rmv.432.CrossRefPubMed

Hirsch HH, Knowles W, Dickenmann M, Passweg J, Klimkait T, Mihatsch MJ, Steiger J: Prospective study of polyomavirus type BK replication and nephropathy in renal-transplant recipients. N Engl J Med. 2002, 347 (7): 488-496. 10.1056/NEJMoa020439.CrossRefPubMed

Fanning E, Knippers R: Structure and function of simian virus 40 large tumor antigen. Annu Rev Biochem. 1992, 61: 55-85. 10.1146/annurev.bi.61.070192.000415.CrossRefPubMed

Pipas JM, Levine AJ: Role of T antigen interactions with p53 in tumorigenesis. Semin Cancer Biol. 2001, 11 (1): 23-30. 10.1006/scbi.2000.0343.CrossRefPubMed

Imperiale MJ: The human polyomaviruses, BKV and JCV: molecular pathogenesis of acute disease and potential role in cancer. Virology. 2000, 267 (1): 1-7. 10.1006/viro.1999.0092.CrossRefPubMed

10.

Casini B, Borgese L, Del Nonno F, Galati G, Izzo L, Caputo M, Perrone Donnorso R, Castelli M, Risuleo G, Visca P: Presence and incidence of DNA sequences of human polyomaviruses BKV and JCV in colorectal tumor tissues. Anticancer Res. 2005, 25 (2A): 1079-1085.PubMed

11.

Enam S, Del Valle L, Lara C, Gan DD, Ortiz-Hidalgo C, Palazzo JP, Khalili K: Association of human polyomavirus JCV with colon cancer: evidence for interaction of viral T-antigen and beta-catenin. Cancer Res. 2002, 62 (23): 7093-7101.PubMed

12.

Del Valle L, Delbue S, Gordon J, Enam S, Croul S, Ferrante P, Khalili K: Expression of JC virus T-antigen in a patient with MS and glioblastoma multiforme. Neurology. 2002, 58 (6): 895-900.CrossRefPubMed

13.

Tognon M, Casalone R, Martini F, De Mattei M, Granata P, Minelli E, Arcuri C, Collini P, Bocchini V: Large T antigen coding sequences of two DNA tumor viruses, BK and SV40, and nonrandom chromosome changes in two glioblastoma cell lines. Cancer Genet Cytogenet. 1996, 90 (1): 17-23. 10.1016/0165-4608(96)00067-2.CrossRefPubMed

14.

Carbone M, Rizzo P, Grimley PM, Procopio A, Mew DJ, Shridhar V, de Bartolomeis A, Esposito V, Giuliano MT, Steinberg SM, Levine AS, Giordano A, Pass HI: Simian virus-40 large-T antigen binds p53 in human mesotheliomas. Nat Med. 1997, 3 (8): 908-912. 10.1038/nm0897-908.CrossRefPubMed

15.

Das D, Shah RB, Imperiale MJ: Detection and expression of human BK virus sequences in neoplastic prostate tissues. Oncogene. 2004, 23 (42): 7031-7046. 10.1038/sj.onc.1207920.CrossRefPubMed

16.

Engels EA, Rollison DE, Hartge P, Baris D, Cerhan JR, Severson RK, Cozen W, Davis S, Biggar RJ, Goedert JJ, Viscidi RP: Antibodies to JC and BK viruses among persons with non-Hodgkin lymphoma. Int J Cancer. 2005, 117 (6): 1013-1019. 10.1002/ijc.21277.CrossRefPubMed

17.

Rollison DE, Engels EA, Halsey NA, Shah KV, Viscidi RP, Helzlsouer KJ: Prediagnostic circulating antibodies to JC and BK human polyomaviruses and risk of non-Hodgkin lymphoma. Cancer Epidemiol Biomarkers Prev. 2006, 15 (3): 543-550. 10.1158/1055-9965.EPI-05-0728.CrossRefPubMed

18.

Imperiale MJ: Oncogenic transformation by the human polyomaviruses. Oncogene. 2001, 20 (54): 7917-7923. 10.1038/sj.onc.1204916.CrossRefPubMed

19.

Tognon M, Corallini A, Martini F, Negrini M, Barbanti-Brodano G: Oncogenic transformation by BK virus and association with human tumors. Oncogene. 2003, 22 (33): 5192-5200. 10.1038/sj.onc.1206550.CrossRefPubMed

20.

Otahal P, Hutchinson SC, Mylin LM, Tevethia MJ, Tevethia SS, Schell TD: Inefficient cross-presentation limits the CD8+ T cell response to a subdominant tumor antigen epitope. J Immunol. 2005, 175 (2): 700-712.CrossRefPubMed

21.

ExPASy Proteomics Server [ http://www.expasy.org ].

22.

NCBI protein-protein BLAST [ www.ncbi.nih.gov/BLAST/Blast.cgi ].

23.

HLA Peptide Binding Predictions [ http://bimas.cit.nih.gov/molbio/hla_bind/ ].

24.

A database of MHC ligands and peptide motifs [ http://www.syfpeithi.de/ ].

25.

Provenzano M, Mocellin S, Marincola FM, Stroncek DF: The Use of Algorithms with a Novel Score Standardization Method for the Selection of Candidate Immunogenic HLA-Specific Peptides Led to the Identification of New Immunogenic HLA-A*0201 Cytomegalovirus Epitopes. ASH Annual Meeting Abstracts. 2004, 104 (11): 2862-

26.

Drexler I, Staib C, Kastenmuller W, Stevanovic S, Schmidt B, Lemonnier FA, Rammensee HG, Busch DH, Bernhard H, Erfle V, Sutter G: Identification of vaccinia virus epitope-specific HLA-A*0201-restricted T cells and comparative analysis of smallpox vaccines. Proc Natl Acad Sci U S A. 2003, 100 (1): 217-222. 10.1073/pnas.262668999.PubMedCentralCrossRefPubMed

27.

Blanchet JS, Valmori D, Dufau I, Ayyoub M, Nguyen C, Guillaume P, Monsarrat B, Cerottini JC, Romero P, Gairin JE: A new generation of Melan-A/MART-1 peptides that fulfill both increased immunogenicity and high resistance to biodegradation: implication for molecular anti-melanoma immunotherapy. J Immunol. 2001, 167 (10): 5852-5861.CrossRefPubMed

28.

Provenzano M, Lim JB, Mocellin S, Monsurro V, Bettinotti M, Marincola FM, Stroncek DF: The matrix protein pp65(341-350): a peptide that induces ex vivo stimulation and in vitro expansion of CMV-specific CD8+ T cells in subjects bearing either HLA-A*2402 or A*0101 allele. Transfusion. 2003, 43 (11): 1567-1574. 10.1046/j.1537-2995.2003.00564.x.CrossRefPubMed

29.

Ghei M, Stroncek DF, Provenzano M: Analysis of memory T lymphocyte activity following stimulation with overlapping HLA-A*2402, A*0101 and Cw*0402 restricted CMV pp65 peptides. J Transl Med. 2005, 3: 23-10.1186/1479-5876-3-23.PubMedCentralCrossRefPubMed

30.

Diamond DJ, York J, Sun JY, Wright CL, Forman SJ: Development of a candidate HLA A*0201 restricted peptide-based vaccine against human cytomegalovirus infection. Blood. 1997, 90 (5): 1751-1767.PubMed

31.

Provenzano M, Mocellin S, Bettinotti M, Preuss J, Monsurro V, Marincola FM, Stroncek D: Identification of immune dominant cytomegalovirus epitopes using quantitative real-time polymerase chain reactions to measure interferon-gamma production by peptide-stimulated peripheral blood mononuclear cells. J Immunother. 2002, 25 (4): 342-351. 10.1097/00002371-200207000-00006.CrossRefPubMed

32.

Livak KJ, Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 2001, 25 (4): 402-408. 10.1006/meth.2001.1262.CrossRefPubMed

33.

Chaux P, Vantomme V, Coulie P, Boon T, van der Bruggen P: Estimation of the frequencies of anti-MAGE-3 cytolytic T-lymphocyte precursors in blood from individuals without cancer. Int J Cancer. 1998, 77 (4): 538-542. 10.1002/(SICI)1097-0215(19980812)77:4<538::AID-IJC11>3.0.CO;2-2.CrossRefPubMed

34.

Horton RM, Cai ZL, Ho SN, Pease LR: Gene splicing by overlap extension: tailor-made genes using the polymerase chain reaction. Biotechniques. 1990, 8 (5): 528-535.PubMed

35.

Manfredi JJ, Prives C: The transforming activity of simian virus 40 large tumor antigen. Biochim Biophys Acta. 1994, 1198 (1): 65-83.PubMed

36.

Dunbar PR, Smith CL, Chao D, Salio M, Shepherd D, Mirza F, Lipp M, Lanzavecchia A, Sallusto F, Evans A, Russell-Jones R, Harris AL, Cerundolo V: A shift in the phenotype of melan-A-specific CTL identifies melanoma patients with an active tumor-specific immune response. J Immunol. 2000, 165 (11): 6644-6652.CrossRefPubMed

37.

Loftus DJ, Castelli C, Clay TM, Squarcina P, Marincola FM, Nishimura MI, Parmiani G, Appella E, Rivoltini L: Identification of epitope mimics recognized by CTL reactive to the melanoma/melanocyte-derived peptide MART-1(27-35). J Exp Med. 1996, 184 (2): 647-657. 10.1084/jem.184.2.647.CrossRefPubMed

38.

Degl'Innocenti E, Grioni M, Boni A, Camporeale A, Bertilaccio MT, Freschi M, Monno A, Arcelloni C, Greenberg NM, Bellone M: Peripheral T cell tolerance occurs early during spontaneous prostate cancer development and can be rescued by dendritic cell immunization. Eur J Immunol. 2005, 35 (1): 66-75. 10.1002/eji.200425531.CrossRefPubMed

39.

Mylin LM, Schell TD, Roberts D, Epler M, Boesteanu A, Collins EJ, Frelinger JA, Joyce S, Tevethia SS: Quantitation of CD8(+) T-lymphocyte responses to multiple epitopes from simian virus 40 (SV40) large T antigen in C57BL/6 mice immunized with SV40, SV40 T-antigen-transformed cells, or vaccinia virus recombinants expressing full-length T antigen or epitope minigenes. J Virol. 2000, 74 (15): 6922-6934. 10.1128/JVI.74.15.6922-6934.2000.PubMedCentralCrossRefPubMed

40.

Schell TD, Lippolis JD, Tevethia SS: Cytotoxic T lymphocytes from HLA-A2.1 transgenic mice define a potential human epitope from simian virus 40 large T antigen. Cancer Res. 2001, 61 (3): 873-879.PubMed

41.

Velders MP, Macedo MF, Provenzano M, Elmishad AG, Holzhutter HG, Carbone M, Kast WM: Human T cell responses to endogenously presented HLA-A*0201 restricted peptides of Simian virus 40 large T antigen. J Cell Biochem. 2001, 82 (1): 155-162. 10.1002/jcb.1148.CrossRefPubMed

42.

Randhawa PS, Popescu I, Macedo C, Zeevi A, Shapiro R, Vats AN, Metes D: Detection of CD8+ T cells sensitized to BK virus large T antigen in healthy volunteers and kidney transplant recipients. Hum Immunol. 2006, 67 (4-5): 298-302. 10.1016/j.humimm.2006.02.031.CrossRefPubMed

43.

Li J, Melenhorst J, Hensel N, Rezvani K, Sconocchia G, Kilical Y, Hou J, Curfman B, Major E, Barrett AJ: T-cell responses to peptide fragments of the BK virus T antigen: implications for cross-reactivity of immune response to JC virus. J Gen Virol. 2006, 87 (Pt 10): 2951-2960. 10.1099/vir.0.82094-0.CrossRefPubMed

44.

Zhu J, Rice PW, Gorsch L, Abate M, Cole CN: Transformation of a continuous rat embryo fibroblast cell line requires three separate domains of simian virus 40 large T antigen. J Virol. 1992, 66 (5): 2780-2791.PubMedCentralPubMed

45.

Provenzano M, Mocellin S, Bonginelli P, Nagorsen D, Kwon SW, Stroncek D: Ex vivo screening for immunodominant viral epitopes by quantitative real time polymerase chain reaction (qRT-PCR). J Transl Med. 2003, 1 (1): 12-10.1186/1479-5876-1-12.PubMedCentralCrossRefPubMed

46.

Provenzano M, Panelli MC, Mocellin S, Bracci L, Sais G, Stroncek DF, Spagnoli GC, Marincola FM: MHC-peptide specificity and T-cell epitope mapping: where immunotherapy starts. Trends Mol Med. 2006, 12 (10): 465-472. 10.1016/j.molmed.2006.08.008.CrossRefPubMed

47.

Appay V, Dunbar PR, Callan M, Klenerman P, Gillespie GM, Papagno L, Ogg GS, King A, Lechner F, Spina CA, Little S, Havlir DV, Richman DD, Gruener N, Pape G, Waters A, Easterbrook P, Salio M, Cerundolo V, McMichael AJ, Rowland-Jones SL: Memory CD8+ T cells vary in differentiation phenotype in different persistent virus infections. Nat Med. 2002, 8 (4): 379-385. 10.1038/nm0402-379.CrossRefPubMed

48.

Krymskaya L, Sharma MC, Martinez J, Haq W, Huang EC, Limaye AP, Diamond DJ, Lacey SF: Cross-reactivity of T lymphocytes recognizing a human cytotoxic T-lymphocyte epitope within BK and JC virus VP1 polypeptides. J Virol. 2005, 79 (17): 11170-11178. 10.1128/JVI.79.17.11170-11178.2005.PubMedCentralCrossRefPubMed

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
Authors: Maurizio Provenzano
Laura Bracci
Stephen Wyler
Tvrtko Hudolin
Giovanni Sais
Rainer Gosert
Paul Zajac
Giorgio Palu'
Michael Heberer
Hans H Hirsch
Giulio C Spagnoli
Publication date: 01-06-2006
Publisher: BioMed Central
Published in: Journal of Translational Medicine / Issue 1/2006
Electronic ISSN: 1479-5876
DOI: https://doi.org/10.1186/1479-5876-4-47

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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

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