1887

Journal of General Virology

Volume 85, Issue 8

Human CD8 T cell responses against five newly identified respiratory syncytial virus-derived epitopes Free

Abstract

CD8 T lymphocytes play a major role in the clearance of respiratory syncytial virus (RSV) infections. To be able to study the primary CTL response in RSV-infected children, epitopes presented by a set of commonly used HLA alleles (HLA-A1, -A3, -B44 and -B51) were searched for. Five epitopes were characterized derived from the matrix (M), non-structural (NS2) and second matrix (M2) proteins of RSV. All epitopes were shown to be processed and presented by RSV-infected antigen-presenting cells. HLA-A1 tetramers for one of these epitopes derived from the M protein were constructed and used to quantify and phenotype the memory CD8 T cell pool in a panel of healthy adult donors. In about 60 % of the donors, CD8 T cells specific for the M protein could be identified. These cells belonged to the memory T cell subset characterized by expression of CD27 and CD28, and down-regulation of CCR7 and CD45RA. The frequency of tetramer-positive cells varied between 0·4 and 3 per 10 CD8 T cells in PBMC of healthy asymptomatic adult donors.

  • Received:
  • Accepted:
  • Published Online:
SGM
Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.80131-0
2004-08-01
2021-03-07
Loading full text...

Full text loading...

/deliver/fulltext/jgv/85/8/vir852365.html?itemId=/content/journal/jgv/10.1099/vir.0.80131-0&mimeType=html&fmt=ahah

References

  1. Alwan W. H., Record F. M., Openshaw P. J. 1992; CD4+ T cells clear virus but augment disease in mice infected with respiratory syncytial virus. Comparison with the effects of CD8+ T cells. Clin Exp Immunol 88:527–536
     [Google Scholar]
  2. Alwan W. H., Kozlowska W. J., Openshaw P. J. 1994; Distinct types of lung disease caused by functional subsets of antiviral T cells. J Exp Med 179:81–89 [CrossRef]
     [Google Scholar]
  3. Appay V., Dunbar P. R., Callan M. 18 other authors 2002; Memory CD8+ T cells vary in differentiation phenotype in different persistent virus infections. Nat Med 8:379–385 [CrossRef]
     [Google Scholar]
  4. Bont L., Heijnen C. J., Kavelaars A., van Aalderen W. M., Brus F., Draaisma J. T., Geelen S. M., van Vught H. J., Kimpen J. L. 1999; Peripheral blood cytokine responses and disease severity in respiratory syncytial virus bronchiolitis. Eur Respir J 14:144–149 [CrossRef]
     [Google Scholar]
  5. Brandenburg A. H., de Waal L., Timmerman H. H., Hoogerhout P., de Swart R. L., Osterhaus A. D. 2000; HLA class I-restricted cytotoxic T-cell epitopes of the respiratory syncytial virus fusion protein. J Virol 74:10240–10244 [CrossRef]
     [Google Scholar]
  6. Brandt C. D., Kim H. W., Arrobio J. O., Jeffries B. C., Wood S. C., Chanock R. M., Parrott R. H. 1973; Epidemiology of respiratory syncytial virus infection in Washington, DC. Composite analysis of eleven consecutive yearly epidemics. Am J Epidemiol 98:355–364
     [Google Scholar]
  7. Callan M. F., Tan L., Annels N., Ogg G. S., Wilson J. D., O'Callaghan C. A., Steven N., McMichael A. J., Rickinson A. B. 1998; Direct visualization of antigen-specific CD8+ T cells during the primary immune response to Epstein–Barr virus in vivo. J Exp Med 187:1395–1402 [CrossRef]
     [Google Scholar]
  8. Cannon M. J., Stott E. J., Taylor G., Askonas B. A. 1987; Clearance of persistent respiratory syncytial virus infections in immunodeficient mice following transfer of primed T cells. Immunology 62:133–138
     [Google Scholar]
  9. Cannon M. J., Openshaw P. J., Askonas B. A. 1988; Cytotoxic T cells clear virus but augment lung pathology in mice infected with respiratory syncytial virus. J Exp Med 168:1163–1168 [CrossRef]
     [Google Scholar]
  10. Cherrie A. H., Anderson K., Wertz G. W., Openshaw P. J. 1992; Human cytotoxic T cells stimulated by antigen on dendritic cells recognize the N, SH, F, M, 22K, and 1b proteins of respiratory syncytial virus. J Virol 66:2102–2110
     [Google Scholar]
  11. de Waal L., Koopman L. P., van Benten I. J., Brandenburg A. H., Mulder P. G., de Swart R. L., Fokkens W. J., Neijens H. J., Osterhaus A. D. 2003; Moderate local and systemic respiratory syncytial virus-specific T-cell responses upon mild or subclinical RSV infection. J Med Virol 70:309–318 [CrossRef]
     [Google Scholar]
  12. Goulder P. J., Lechner F., Klenerman P., McIntosh K., Walker B. D. 2000; Characterization of a novel respiratory syncytial virus-specific human cytotoxic T-lymphocyte epitope. J Virol 74:7694–7697 [CrossRef]
     [Google Scholar]
  13. Graham B. S., Bunton L. A., Wright P. F., Karzon D. T. 1991; Role of T lymphocyte subsets in the pathogenesis of primary infection and rechallenge with respiratory syncytial virus in mice. J Clin Invest 88:1026–1033 [CrossRef]
     [Google Scholar]
  14. Hall C. B., Powell K. R., MacDonald N. E., Gala C. L., Menegus M. E., Suffin S. C., Cohen H. J. 1986; Respiratory syncytial viral infection in children with compromised immune function. N Engl J Med 315:77–81 [CrossRef]
     [Google Scholar]
  15. He X. S., Mahmood K., Maecker H. T., Holmes T. H., Kemble G. W., Arvin A. M., Greenberg H. B. 2003; Analysis of the frequencies and of the memory T cell phenotypes of human CD8+ T cells specific for influenza A viruses. J Infect Dis 187:1075–1084 [CrossRef]
     [Google Scholar]
  16. Hislop A. D., Gudgeon N. H., Callan M. F., Fazou C., Hasegawa H., Salmon M., Rickinson A. B. 2001; EBV-specific CD8+ T cell memory: relationships between epitope specificity, cell phenotype, and immediate effector function. J Immunol 167:2019–2029 [CrossRef]
     [Google Scholar]
  17. Isaacs D., Bangham C. R., McMichael A. J. 1987; Cell-mediated cytotoxic response to respiratory syncytial virus in infants with bronchiolitis. Lancet ii:769–771
     [Google Scholar]
  18. Mbawuike I. N., Wells J., Byrd R., Cron S. G., Glezen W. P., Piedra P. A. 2001; HLA-restricted CD8+ cytotoxic T lymphocyte, interferon- γ , and interleukin-4 responses to respiratory syncytial virus infection in infants and children. J Infect Dis 183:687–696 [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. Rock M. T., Crowe J. E. 2003; Identification of a novel human leucocyte antigen-A*01-restricted cytotoxic T-lymphocyte epitope in the respiratory syncytial virus fusion protein. Immunology 108:474–480 [CrossRef]
     [Google Scholar]
  21. Salkind A. R., McCarthy D. O., Nichols J. E., Domurat F. M., Walsh E. E., Roberts N. J. Jr 1991; Interleukin-1-inhibitor activity induced by respiratory syncytial virus: abrogation of virus-specific and alternate human lymphocyte proliferative responses. J Infect Dis 163:71–77 [CrossRef]
     [Google Scholar]
  22. Schlender J., Walliser G., Fricke J., Conzelmann K. K. 2002; Respiratory syncytial virus fusion protein mediates inhibition of mitogen-induced T-cell proliferation by contact. J Virol 76:1163–1170 [CrossRef]
     [Google Scholar]
  23. Shay D. K., Holman R. C., Newman R. D., Liu L. L., Stout J. W., Anderson L. J. 1999; Bronchiolitis-associated hospitalizations among US children, 1980–1996. JAMA 282:1440–1446 [CrossRef]
     [Google Scholar]
  24. Sigurs N., Bjarnason R., Sigurbergsson F., Kjellman B. 2000; Respiratory syncytial virus bronchiolitis in infancy is an important risk factor for asthma and allergy at age 7. Am J Respir Crit Care Med 161:1501–1507 [CrossRef]
     [Google Scholar]
  25. Stein R. T., Sherrill D., Morgan W. J., Holberg C. J., Halonen M., Taussig L. M., Wright A. L., Martinez F. D. 1999; Respiratory syncytial virus in early life and risk of wheeze and allergy by age 13 years. Lancet 354:541–545 [CrossRef]
     [Google Scholar]
  26. Urbani S., Boni C., Missale G., Elia G., Cavallo C., Massari M., Raimondo G., Ferrari C. 2002; Virus-specific CD8+ lymphocytes share the same effector-memory phenotype but exhibit functional differences in acute hepatitis B and C. J Virol 76:12423–12434 [CrossRef]
     [Google Scholar]
  27. van Lier R. A., ten Berge I. J., Gamadia L. E. 2003; Human CD8+ T-cell differentiation in response to viruses. Nat Rev Immunol 3:931–939 [CrossRef]
     [Google Scholar]
  28. Venter M., Rock M., Puren A. J., Tiemessen C. T., Crowe J. E. Jr 2003; Respiratory syncytial virus nucleoprotein-specific cytotoxic T-cell epitopes in a South African population of diverse HLA types are conserved in circulating field strains. J Virol 77:7319–7329 [CrossRef]
     [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.80131-0
Loading
Human CD8+ T cell responses against five newly identified respiratory syncytial virus-derived epitopes
J. Gen. Virol. 85, 2365 (2004); https://doi.org/10.1099/vir.0.80131-0
/content/journal/jgv/10.1099/vir.0.80131-0
/content/journal/jgv/10.1099/vir.0.80131-0
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