1887

Abstract

Acute enteroviral infections ranging from meningitis, pancreatitis to myocarditis are common and normally well controlled by the host immune system comprising virus-specific CD8 cytotoxic T lymphocytes (CTL). However, in some patients enteroviruses and especially coxsackieviruses of group B are capable of inducing severe chronic forms of diseases such as chronic myocarditis. Currently, it is not known whether divergences in the CTL-related immune response may contribute to the different outcome and course of enterovirus myocarditis. A pre-requisite for the study of CTL reactions in patients with acute and chronic myocarditis is the identification of CTL epitopes. In order to define dominant enterovirus CTL epitopes, we have screened, by using gamma interferon (IFN-) ELISPOT, 62 HLA-A*01- and 59 HLA-A*02-positive healthy blood donors for pre-existing CTL reactions against 12 HLA-A*01 and 20 HLA-A*02 predicted CTL epitopes derived from coxsackieviruses of group B. Positive CTL reactions were verified by FACS analysis in a combined major histocompatibility complex-tetramer IFN- staining. A total of 14.8 % of all donors reacted against one of the three identified epitopes MLDGHLIAFDY, YGDDVIASY or GIIYIIYKL. The HLA-A*02-restricted epitope ILMNDQEVGV was recognized by 25 % of all tested blood donors. For this peptide, we could demonstrate specific granzyme B secretion, a strong cytolytic potential and endogenous processing. All four epitopes were homologous in 36–92 % of group B enteroviruses, providing a strong basis for monitoring the divergence of T-cell-based immune responses in enterovirus-induced acute and chronic diseases.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.2008/000711-0
2008-09-01
2024-12-06
Loading full text...

Full text loading...

/deliver/fulltext/jgv/89/9/2090.html?itemId=/content/journal/jgv/10.1099/vir.0.2008/000711-0&mimeType=html&fmt=ahah

References

  1. Altman J. D., Moss P. A., Goulder P. J., Barouch D. H., McHeyzer-Williams M. G., Bell J. I., McMichael A. J., Davis M. M. 1996; Phenotypic analysis of antigen-specific T lymphocytes. Science 274:94–96 [CrossRef]
    [Google Scholar]
  2. Baboonian C., Davies M. J., Booth J. C., McKenna W. J. 1997; Coxsackie B viruses and human heart disease. Curr Top Microbiol Immunol 223:31–52
    [Google Scholar]
  3. Boucek M. M., Faro A., Novick R. J., Bennett L. E., Keck B. M., Hosenpud J. D. 2001; The registry of the international society for heart and lung transplantation: fourth official pediatric report–2000. J Heart Lung Transplant 20:39–52 [CrossRef]
    [Google Scholar]
  4. Bouslama L., Nasri D., Chollet L., Belguith K., Bourlet T., Aouni M., Pozzetto B., Pillet S. 2007; Natural recombination event within the capsid genomic region leading to a chimeric strain of human enterovirus B. J Virol 81:8944–8952 [CrossRef]
    [Google Scholar]
  5. Britten C. M., Gouttefangeas C., Welters M. J., Pawelec G., Koch S., Ottensmeier C., Mander A., Walter S., Paschen A. other authors 2008; The CIMT-monitoring panel: a two-step approach to harmonize the enumeration of antigen-specific CD8+ T lymphocytes by structural and functional assays. Cancer Immunol Immunother 57:289–302 [CrossRef]
    [Google Scholar]
  6. Chua B. H., McMinn P. C., Lam S. K., Chua K. B. 2001; Comparison of the complete nucleotide sequences of echovirus 7 strain UMMC and the prototype (Wallace) strain demonstrates significant genetic drift over time. J Gen Virol 82:2629–2639
    [Google Scholar]
  7. Codd M. B., Sugrue D. D., Gersh B. J., Melton L. J. III 1989; Epidemiology of idiopathic dilated and hypertrophic cardiomyopathy. A population-based study in Olmsted County Minnesota: 1975–1984 Circulation 80:564–572 [CrossRef]
    [Google Scholar]
  8. Coulie P. G., Karanikas V., Colau D., Lurquin C., Landry C., Marchand M., Dorval T., Brichard V., Boon T. 2001; A monoclonal cytolytic T-lymphocyte response observed in a melanoma patient vaccinated with a tumor-specific antigenic peptide encoded by gene MAGE-3. Proc Natl Acad Sci U S A 98:10290–10295 [CrossRef]
    [Google Scholar]
  9. Hermans I. F., Silk J. D., Yang J., Palmowski M. J., Gileadi U., McCarthy C., Salio M., Ronchese F., Cerundolo V. 2004; The VITAL assay: a versatile fluorometric technique for assessing CTL- and NKT-mediated cytotoxicity against multiple targets in vitro and in vivo. J Immunol Methods 285:25–40 [CrossRef]
    [Google Scholar]
  10. Kemball C. C., Harkins S., Whitton J. L. 2008; Enumeration and functional evaluation of virus-specific CD4+ and CD8+ T cells in lymphoid and peripheral sites of coxsackievirus B3 infection. J Virol 82:4331–4342 [CrossRef]
    [Google Scholar]
  11. Khetsuriani N., Oberst A., Pallansch S., A. M. 2006; Lamonte-Fowlkes. Centers for Disease Control and Prevention. Enterovirus surveillance–United States, 1970–2005. MMWR Surveill Summ 55:1–20
    [Google Scholar]
  12. Kim K. S., Hufnagel G., Chapman N. M., Tracy S. 2001; The group B coxsackieviruses and myocarditis. Rev Med Virol 11:355–368 [CrossRef]
    [Google Scholar]
  13. Klingel K., Schnorr J. J., Sauter M., Szalay G., Kandolf R. 2003; β 2-microglobulin-associated regulation of interferon- γ and virus-specific immunoglobulin G confer resistance against the development of chronic coxsackievirus myocarditis. Am J Pathol 162:1709–1720 [CrossRef]
    [Google Scholar]
  14. Klingel K., Sauter M., Bock C. T., Szalay G., Schnorr J. J., Kandolf R. 2004; Molecular pathology of inflammatory cardiomyopathy. Med Microbiol Immunol 193:101–107 [CrossRef]
    [Google Scholar]
  15. Knowlton K. U., Badorff C. 1999; The immune system in viral myocarditis: maintaining the balance. Circ Res 85:559–561 [CrossRef]
    [Google Scholar]
  16. McManus B. M., Chow L. H., Radio S. J., Tracy S. M., Beck M. A., Chapman N. M., Klingel K., Kandolf R. 1991; Progress and challenges in the pathological diagnosis of myocarditis. Eur Heart J 12:Suppl. D18–21
    [Google Scholar]
  17. Modlin J. F., Rotbart H. A. 1997; Group B coxsackie disease in children. Curr Top Microbiol Immunol 223:53–80
    [Google Scholar]
  18. Opavsky M. A., Penninger J., Aitken K., Wen W. H., Dawood F., Mak T., Liu P. 1999; Susceptibility to myocarditis is dependent on the response of αβ T lymphocytes to coxsackieviral infection. Circ Res 85:551–558 [CrossRef]
    [Google Scholar]
  19. Rammensee H., Bachmann J., Emmerich N. P., Bachor O. A., Stevanovic S. 1999; syfpeithi: database for MHC ligands and peptide motifs. Immunogenetics 50:213–219 [CrossRef]
    [Google Scholar]
  20. Rotbart H. A. 1995; Enteroviral infections of the central nervous system. Clin Infect Dis 20:971–981 [CrossRef]
    [Google Scholar]
  21. Rotbart H. A., McCracken G. H. Jr, Whitley R. J., Modlin J. F., Cascino M., Shah S., Blum D. 1999; Clinical significance of enteroviruses in serious summer febrile illnesses of children. Pediatr Infect Dis J 18:869–874 [CrossRef]
    [Google Scholar]
  22. Saeed M., Zaidi S. Z., Naeem A., Masroor M., Sharif S., Shaukat S., Angez M., Khan A. 2007; Epidemiology and clinical findings associated with enteroviral acute flaccid paralysis in Pakistan. BMC Infect Dis 7:6 [CrossRef]
    [Google Scholar]
  23. Schirle M., Keilholz W., Weber B., Gouttefangeas C., Dumrese T., Becker H. D., Stevanovic S., Rammensee H. G. 2000; Identification of tumor-associated MHC class I ligands by a novel T cell-independent approach. Eur J Immunol 30:2216–2225 [CrossRef]
    [Google Scholar]
  24. Schmitz M., Wehner R., Stevanovic S., Kiessling A., Rieger M. A., Temme A., Bachmann M., Rieber E. P., Weigle B. 2007; Identification of a naturally processed T cell epitope derived from the glioma-associated protein SOX11. Cancer Lett 245:331–336 [CrossRef]
    [Google Scholar]
  25. Simmonds P., Welch J. 2006; Frequency and dynamics of recombination within different species of human enteroviruses. J Virol 80:483–493 [CrossRef]
    [Google Scholar]
  26. Slifka M. K., Pagarigan R., Mena I., Feuer R., Whitton J. L. 2001; Using recombinant coxsackievirus B3 to evaluate the induction and protective efficacy of CD8+ T cells during picornavirus infection. J Virol 75:2377–2387 [CrossRef]
    [Google Scholar]
  27. Stanway G., Brown F., Christian P., Hovi T., Hyypiä T., King A. M. Q., Knowles N. J., Lemon S. M., Minor P. D. other authors 2005; Family Picornaviridae . In Virus Taxonomy. Eighth Report of the International Committee on Taxonomy of Viruses pp 757–778Edited by Fauquet C. M., Mayo M. A., Maniloff J., Desselberger U., Ball. London: Elsevier/Academic Press;
    [Google Scholar]
  28. Strikas R. A., Anderson L. J., Parker R. A. 1986; Temporal and geographic patterns of isolates of nonpolio enterovirus in the United States, 1970–1983. J Infect Dis 153:346–351 [CrossRef]
    [Google Scholar]
  29. Varela-Calvino R., Skowera A., Arif S., Peakman M. 2004; Identification of a naturally processed cytotoxic CD8 T-cell epitope of coxsackievirus B4, presented by HLA-A2.1 and located in the PEVKEK region of the P2C nonstructural protein. J Virol 78:13399–13408 [CrossRef]
    [Google Scholar]
  30. Walter S., Bioley G., Bühring H. J., Koch S., Wernet D., Zippelius A., Pawelec G., Romero P., Stevanovic S. other authors 2005; High frequencies of functionally impaired cytokeratin 18-specific CD8+ T cells in healthy HLA-A2+ donors. Eur J Immunol 35:2876–2885 [CrossRef]
    [Google Scholar]
/content/journal/jgv/10.1099/vir.0.2008/000711-0
Loading
/content/journal/jgv/10.1099/vir.0.2008/000711-0
Loading

Data & Media loading...

Supplements

Supplementary material 1

PDF
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