Display options
Cite
Ramaswami B, Popescu I, Macedo C, et al. The polyomavirus BK large T-antigen-derived peptide elicits an HLA-DR promiscuous and polyfunctional CD4+ T-cell response. Clin Vaccine Immunol. 2011;18(5):815-24doi: 10.1128/CVI.00487-10.
Ramaswami, B., Popescu, I., Macedo, C., Luo, C., Shapiro, R., Metes, D., Chalasani, G., & Randhawa, P. S. (2011). The polyomavirus BK large T-antigen-derived peptide elicits an HLA-DR promiscuous and polyfunctional CD4+ T-cell response. Clinical and vaccine immunology : CVI, 18(5), 815-24. https://doi.org/10.1128/CVI.00487-10
Ramaswami, Bala, et al. "The polyomavirus BK large T-antigen-derived peptide elicits an HLA-DR promiscuous and polyfunctional CD4+ T-cell response." Clinical and vaccine immunology : CVI vol. 18,5 (2011): 815-24. doi: https://doi.org/10.1128/CVI.00487-10
Ramaswami B, Popescu I, Macedo C, Luo C, Shapiro R, Metes D, Chalasani G, Randhawa PS. The polyomavirus BK large T-antigen-derived peptide elicits an HLA-DR promiscuous and polyfunctional CD4+ T-cell response. Clin Vaccine Immunol. 2011 May;18(5):815-24. doi: 10.1128/CVI.00487-10. Epub 2011 Mar 02. PMID: 21367979; PMCID: PMC3122532.
Copy Download .nbib Format: NLM
Share it on

Clin Vaccine Immunol. 2011 May;18(5):815-24. doi: 10.1128/CVI.00487-10. Epub 2011 Mar 02.

The polyomavirus BK large T-antigen-derived peptide elicits an HLA-DR promiscuous and polyfunctional CD4+ T-cell response.

Clinical and vaccine immunology : CVI

Bala Ramaswami, Iulia Popescu, Camila Macedo, Chunqing Luo, Ron Shapiro, Diana Metes, Geetha Chalasani, Parmjeet S Randhawa

Affiliations

  1. Division of Transplant Pathology, Department of Pathology, University of Pittsburgh, Pittsburgh, PA 15213, USA. [email protected]

PMID: 21367979 PMCID: PMC3122532 DOI: 10.1128/CVI.00487-10

Abstract

BK virus (BKV) nephropathy and hemorrhagic cystitis are increasingly recognized causes of disease in renal and hematopoietic stem cell transplant recipients, respectively. Functional characterization of the immune response to BKV is important for clinical diagnosis, prognosis, and vaccine design. A peptide mix (PepMix) and overlapping (OPP) or random (RPP) peptide pools derived from BKV large T antigen (LTA) were used to restimulate 14-day-expanded peripheral blood mononuclear cells (PBMC) from 27 healthy control subjects in gamma interferon (IFN-γ)-specific enzyme-linked immunospot (ELISPOT) assays. A T-cell response to LTA PepMix was detected in 15/27 subjects. A response was frequently observed with peptides derived from the helicase domain (9/15 subjects), while the DNA binding and host range domains were immunologically inert (0/15 subjects). For all nine subjects who responded to LTA peptide pools, the immune response could be explained largely by a 15-mer peptide designated P313. P313-specific CD4(+) T-cell clones demonstrated (i) stringent LTA peptide specificity; (ii) promiscuous recognition in the context of HLA-DR alleles; (iii) cross recognition of homologous peptides from the polyomavirus simian virus 40 (SV40); (iv) an effector memory phenotype, CD107a expression, and intracellular production of IFN-γ and tumor necrosis factor alpha (TNF-α); (v) cytotoxic activity in a chromium release assay; and (vi) the ability to directly present cognate antigen to autologous T cells. In conclusion, T-cell-mediated immunity to BKV in healthy subjects is associated with a polyfunctional population of CD4(+) T cells with dual T-helper and T-cytotoxic properties. HLA class II promiscuity in antigen presentation makes the targeted LTA peptide sequence a suitable candidate for inclusion in immunotherapy protocols.

References

  1. Blood. 2004 Mar 15;103(6):2238-47 - PubMed
  2. Hum Immunol. 2000 Dec;61(12):1219-32 - PubMed
  3. Eur J Immunol. 2007 Sep;37(9):2419-33 - PubMed
  4. J Immunol. 2002 Dec 15;169(12):6928-34 - PubMed
  5. J Transl Med. 2006 Nov 10;4:47 - PubMed
  6. J Virol. 1995 Nov;69(11):6665-77 - PubMed
  7. J Virol. 2008 Jan;82(1):546-54 - PubMed
  8. Virology. 1995 Apr 1;208(1):159-72 - PubMed
  9. J Virol. 2007 Feb;81(3):1412-23 - PubMed
  10. J Gen Virol. 2006 Oct;87(Pt 10):2951-2960 - PubMed
  11. Am J Transplant. 2007 Dec;7(12):2727-35 - PubMed
  12. Curr Protoc Immunol. 2002 May;Chapter 7:Unit 7.19 - PubMed
  13. Clin Vaccine Immunol. 2006 Sep;13(9):1057-63 - PubMed
  14. J Immunol. 1991 Aug 1;147(3):774-80 - PubMed
  15. Transpl Infect Dis. 2006 Jun;8(2):59-61 - PubMed
  16. J Immunol. 2002 Jan 1;168(1):499-504 - PubMed
  17. J Virol. 2008 Apr;82(8):4102-14 - PubMed
  18. Virology. 2006 Jun 20;350(1):128-36 - PubMed
  19. J Immunol. 1989 Jul 15;143(2):762-9 - PubMed
  20. Nature. 1988 Aug 11;334(6182):530-2 - PubMed
  21. Viral Immunol. 2007 Sep;20(3):379-88 - PubMed
  22. Biol Blood Marrow Transplant. 2009 Mar;15(3):391-2 - PubMed
  23. Immunol Res. 2001;23(1):1-21 - PubMed
  24. J Immunol. 2002 Jun 1;168(11):5954-8 - PubMed
  25. Blood. 2007 Mar 1;109(5):2049-57 - PubMed
  26. Kidney Int. 2006 Feb;69(4):655-62 - PubMed
  27. J Clin Virol. 2008 Jun;42(2):198-202 - PubMed
  28. Vaccine. 2010 Mar 16;28(13):2556-64 - PubMed
  29. Hum Immunol. 2006 Apr-May;67(4-5):298-302 - PubMed
  30. J Virol. 2006 Apr;80(7):3495-505 - PubMed
  31. Methods. 2003 Mar;29(3):260-9 - PubMed
  32. J Exp Med. 2006 Dec 25;203(13):2865-77 - PubMed
  33. J Virol. 2005 Sep;79(17):11170-8 - PubMed
  34. J Virol. 2003 Nov;77(22):11918-26 - PubMed
  35. Am J Transplant. 2008 May;8(5):990-9 - PubMed
  36. Methods. 2003 Mar;29(3):270-81 - PubMed
  37. Transplantation. 2009 Apr 15;87(7):1019-26 - PubMed
  38. Cell. 1988 Aug 12;54(4):561-75 - PubMed
  39. Transpl Int. 2009 Jun;22(6):626-34 - PubMed
  40. J Immunol. 2004 Nov 1;173(9):5852-62 - PubMed
  41. Am J Pathol. 2010 May;176(5):2107-12 - PubMed
  42. Lab Invest. 2003 May;83(5):683-95 - PubMed
  43. Am J Transplant. 2009 Dec;9 Suppl 4:S136-46 - PubMed
  44. Immunology. 2010 Apr;129(4):496-505 - PubMed
  45. Curr Opin Immunol. 2008 Jun;20(3):339-43 - PubMed
  46. J Immunol. 2007 Jul 15;179(2):1303-12 - PubMed
  47. Hum Immunol. 2009 Sep;70(9):722-8 - PubMed
  48. Curr Protoc Immunol. 2001 May;Chapter 7:Unit 7.18 - PubMed
  49. Int J Immunopathol Pharmacol. 2005 Apr-Jun;18(2):309-16 - PubMed

Substances

MeSH terms

Publication Types