1887

Abstract

Infection with BK virus (BKV) induces both humoral and cellular immunity, but the viral antigens of T-antigen (T-ag) stimulating T-cell responses are largely unknown. To identify BKV-specific T cells in healthy individuals, peripheral blood lymphocytes were cultured with autologous dendritic cells (DCs) loaded with BKV lysate and T cells were screened for intracellular gamma interferon production after stimulation with an overlapping 15mer peptide library of the BKV T-ag. Among many immunogenic peptides identified, four T-ag peptides were identified as candidate major histocompatibility complex class I and II T-cell epitopes, restricted to human leukocyte antigen (HLA)-B*0702, -B*08, -DRB1*0301 and -DRB1*0901. Further, a candidate 9mer peptide, LPLMRKAYL, was confirmed to be restricted to HLA-B*0702 and -B*08. Because the polyomaviruses BKV, JC virus (JCV) and (SV40) share extensive sequence similarity in the immunogenic proteins T-ag and VP1, it was hypothesized that, in humans, these proteins contain conserved cytotoxic T-lymphocyte (CTL) target epitopes. Four HLA-restricted conserved epitopes of BKV, JCV and SV40 were identified: HLA-B*07, -B*08 and -DRB1*0901 for T-ag and -A*0201 for VP1. T cells cultured that were specific for one viral antigen recognized other conserved epitopes. CTLs generated from BKV T-ag and VP1 peptide were cytotoxic to DC targets pulsed with either BKV or JCV. Therefore, infection by one of the two viruses (BKV and JCV) could establish cross-immunity against the other. Although cross-cytotoxicity experiments were not performed with SV40, cross-recognition data from conserved antigen epitopes of polyomaviruses suggest strongly that cross-immunity might also exist among the three viruses.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.82094-0
2006-10-01
2021-03-06
Loading full text...

Full text loading...

/deliver/fulltext/jgv/87/10/2951.html?itemId=/content/journal/jgv/10.1099/vir.0.82094-0&mimeType=html&fmt=ahah

References

  1. Acierno P. M., Newton D. A., Brown E. A., Maes L. A., Baatz J. E., Gattoni-Celli S. 2003; Cross-reactivity between HLA-A2-restricted FLU-M1 : 58–66 and HIV p17 GAG : 77–85 epitopes in HIV-infected and uninfected individuals. J Transl Med 1:3 [CrossRef]
    [Google Scholar]
  2. Bergsagel D. J., Finegold M. J., Butel J. S., Kupsky W. J., Garcea R. L. 1992; DNA sequences similar to those of simian virus 40 in ependymomas and choroid plexus tumors of childhood. N Engl J Med 326:988–993 [CrossRef]
    [Google Scholar]
  3. Braun W. E. 2003; BK polyomavirus: a newly recognized threat to transplanted kidneys. Cleve Clin J Med 70:1056–1068 [CrossRef]
    [Google Scholar]
  4. Butel J. S., Lednicky J. A. 1999; Cell and molecular biology of simian virus 40: implications for human infections and disease. J Natl Cancer Inst 91:119–134 [CrossRef]
    [Google Scholar]
  5. Campbell A. E., Foley F. L., Tevethia S. S. 1983; Demonstration of multiple antigenic sites of the SV40 transplantation rejection antigen by using cytotoxic T lymphocyte clones. J Immunol 130:490–492
    [Google Scholar]
  6. Carbone M., Pass H. I., Rizzo P., Marinetti M., Di Muzio M., Mew D. J., Levine A. S., Procopio A. 1994; Simian virus 40-like DNA sequences in human pleural mesothelioma. Oncogene 9:1781–1790
    [Google Scholar]
  7. Carbone M., Rizzo P., Procopio A. & 12 other authors 1996; SV40-like sequences in human bone tumors. Oncogene 13:527–535
    [Google Scholar]
  8. Chen Y., Trofe J., Gordon J., Du Pasquier R. A., Roy-Chaudhury P., Kuroda M. J., Woodle E. S., Khalili K., Koralnik I. J. 2006; Interplay of cellular and humoral immune responses against BK virus in kidney transplant recipients with polyomavirus nephropathy. J Virol 80:3495–3505 [CrossRef]
    [Google Scholar]
  9. Comoli P., Basso S., Azzi A. & 10 other authors 2003; Dendritic cells pulsed with polyomavirus BK antigen induce ex vivo polyoma BK virus-specific cytotoxic T-cell lines in seropositive healthy individuals and renal transplant recipients. J Am Soc Nephrol 14:3197–3204 [CrossRef]
    [Google Scholar]
  10. Deckhut A. M., Tevethia M. J., Haggerty S., Frisque R. J., Tevethia S. S. 1991; Localization of common cytotoxic T lymphocyte recognition epitopes on simian papovavirus SV40 and human papovavirus JC virus T antigens. Virology 183:122–132 [CrossRef]
    [Google Scholar]
  11. Du Pasquier R. A., Schmitz J. E., Jean-Jacques J., Zheng Y., Gordon J., Khalili K., Letvin N. L., Koralnik I. J. 2004; Detection of JC virus-specific cytotoxic T lymphocytes in healthy individuals. J Virol 78:10206–10210 [CrossRef]
    [Google Scholar]
  12. Evavold B. D., Allen P. M. 1991; Separation of IL-4 production from Th cell proliferation by an altered T cell receptor ligand. Science 252:1308–1310 [CrossRef]
    [Google Scholar]
  13. Evavold B. D., Sloan-Lancaster J., Hsu B. L., Allen P. M. 1993; Separation of T helper 1 clone cytolysis from proliferation and lymphokine production using analog peptides. J Immunol 150:3131–3140
    [Google Scholar]
  14. Gulukota K., Sidney J., Sette A., DeLisi C. 1997; Two complementary methods for predicting peptides binding major histocompatibility complex molecules. J Mol Biol 267:1258–1267 [CrossRef]
    [Google Scholar]
  15. Hamilton R. S., Gravell M., Major E. O. 2000; Comparison of antibody titers determined by hemagglutination inhibition (HI) and enzyome immunoassay for JC virus and BK virus. J Clin Microbiol 38:105–109
    [Google Scholar]
  16. Hemmer B., Gran B., Zhao Y. & 12 other authors 1999; Identification of candidate T-cell epitopes and molecular mimics in chronic Lyme disease. Nat Med 5:1375–1382 [CrossRef]
    [Google Scholar]
  17. Hensel N., Melenhorst J. J., Bradstock K., Schwarer A. P., Eniafe R., Nakamura R., Barrett A. J. 2002; Flow cytometric quantitation and characterization of the T-lymphocyte memory response to CMV in healthy donors. Cytotherapy 4:29–40 [CrossRef]
    [Google Scholar]
  18. Imperiale M. J. 2001; The human polyomaviruses: an overview. In Human Polyomaviruses: Molecular and Clinical Perspectives pp  53–71 Edited by Khalili K., Stoner G. L. New York: Wiley-Liss;
    [Google Scholar]
  19. Jedema I., van der Werff N. M., Barge R. M. Y., Willemze R., Falkenburg J. H. F. 2004; New CFSE-based assay to determine susceptibility to lysis by cytotoxic T cells of leukemic precursor cells within a heterogeneous target cell population. Blood 103:2677–2682 [CrossRef]
    [Google Scholar]
  20. Koralnik I. J. 2002; Overview of the cellular immunity against JC virus in progressive multifocal leukoencephalopathy. J Neurovirol 8 (Suppl. 2):59–65 [CrossRef]
    [Google Scholar]
  21. Krymskaya L., Sharma M. C., Martinez J., Haq W., Huang E. C., Limaye A. P., Diamond D. J., Lacey S. F. 2005; Cross-reactivity of T lymphocytes recognizing a human cytotoxic T-lymphocyte epitope within BK and JC virus VP1 polypeptides. J Virol 79:11170–11178 [CrossRef]
    [Google Scholar]
  22. Lee S. P., Thomas W. A., Murray R. J., Khanim F., Kaur S., Young L. S., Rowe M., Kurilla M., Rickinson A. B. 1993; HLA A2.1-restricted cytotoxic T cells recognizing a range of Epstein-Barr virus isolates through a defined epitope in latent membrane protein LMP2. J Virol 67:7428–7435
    [Google Scholar]
  23. Lee S. P., Tierney R. J., Thomas W. A., Brooks J. M., Rickinson A. B. 1997; Conserved CTL epitopes within EBV latent membrane protein 2: a potential target for CTL-based tumor therapy. J Immunol 158:3325–3334
    [Google Scholar]
  24. Li J., Hensel N., Melenhorst J. J., Mielke S., Barrett A. J. 2005; Selection of antigen-specific T cells on a monocyte APC layer for generation of viral antigen-specific T cells. In Cytotherapy vol. 7, Suppl. 1, abstract 106 Vancouver: International Society for Cellualar Therapy;
    [Google Scholar]
  25. Loftus D. J., Chen Y., Covell D. G., Engelhard V. H., Appella E. 1997; Differential contact of disparate class I/peptide complexes as the basis for epitope cross-recognition by a single T cell receptor. J Immunol 158:3651–3658
    [Google Scholar]
  26. Oldstone M. B. A. 1987; Molecular mimicry and autoimmune disease. Cell 50:819–820 [CrossRef]
    [Google Scholar]
  27. Pipas J. M. 1992; Common and unique features of T antigens encoded by the polyomavirus group. J Virol 66:3979–3985
    [Google Scholar]
  28. Shivapurkar N., Harada K., Reddy J. & 7 other authors 2002; Presence of simian virus 40 DNA sequences in human lymphomas. Lancet 359:851–852 [CrossRef]
    [Google Scholar]
  29. Sloan-Lancaster J., Allen P. M. 1996; Altered peptide ligand-induced partial T cell activation: molecular mechanisms and role in T cell biology. Annu Rev Immunol 14:1–27 [CrossRef]
    [Google Scholar]
  30. Sloan-Lancaster J., Evavold B. D., Allen P. M. 1993; Induction of T-cell anergy by altered T-cell-receptor ligand on live antigen-presenting cells. Nature 363:156–159 [CrossRef]
    [Google Scholar]
  31. Testa J. R., Carbone M., Hirvonen A. & 7 other authors 1998; A multi-institutional study confirms the presence and expression of simian virus 40 in human malignant mesotheliomas. Cancer Res 58:4505–4509
    [Google Scholar]
  32. Tevethia S. S., Mylin L., Newmaster R., Epler M., Lednicky J. A., Butel J. S., Tevethia M. J. 1998; Cytotoxic T lymphocyte recognition sequences as markers for distinguishing among tumour antigens encoded by SV40, BKV and JCV. Dev Biol Stand 94:329–339
    [Google Scholar]
  33. Vilchez R. A., Madden C. R., Kozinetz C. A., Halvorson S. J., White Z. S., Jorgensen J. L., Finch C. J., Butel J. S. 2002; Association between simian virus 40 and non-Hodgkin lymphoma. Lancet 359:817–823 [CrossRef]
    [Google Scholar]
  34. Wedemeyer H., Mizukoshi E., Davis A. R., Bennink J. R., Rehermann B. 2001; Cross-reactivity between hepatitis C virus and influenza A virus determinant-specific cytotoxic T cells. J Virol 75:11392–11400 [CrossRef]
    [Google Scholar]
  35. Yewdell J. W., Bennink J. R. 1999; Immunodominance in major histocompatibility complex class I-restricted T lymphocyte responses. Annu Rev Immunol 17:51–88 [CrossRef]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.82094-0
Loading
/content/journal/jgv/10.1099/vir.0.82094-0
Loading

Data & Media loading...

Most cited this month Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error