1887

Abstract

We describe 15-mer peptide P8:F92–106 from the F protein of respiratory syncytial virus (RSV) that can act as an MHC class I-restricted (H-2K) epitope for RSV-specific CD8 CTL. This peptide is interesting because not only is it the first murine CTL epitope to be identified in the F protein but also because it does not contain a known allele-specific motif, as all 15 amino acids appear to be required for effective presentation to CTL. In MHC class I refolding experiments, peptide P8:F92–106 induced complex formation with H-2K heavy chains and β-microglobulin. Immunization of BALB/c mice with P8:F92–106 resulted in the induction of peptide and RSV-specific CTL responses as well as peptide-specific proliferative responses. Following intranasal challenge with RSV, P8:F92–106-immunized mice showed a significant reduction in viral load in the lungs compared to that seen in unimmunized mice. Furthermore, passive transfer of purified CD8 lymphocytes into BALB/c mice prior to challenge with RSV also resulted in a reduction in the virus load in lungs of challenged mice. These results indicate the potential of synthetic peptide epitopes for the induction of protective immune responses against RSV infection.

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2002-02-01
2024-04-18
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References

  1. Alwan W. H., Record F. M., Openshaw P. J. 1993; Phenotypic and functional characterization of T cell lines specific for individual respiratory syncytial virus proteins. Journal of Immunology 150:5211–5218
    [Google Scholar]
  2. Bangham C. R., Openshaw P. J., Ball L. A., King A. M., Wertz G. W., Askonas B. A. 1986; Human and murine cytotoxic T cells specific to respiratory syncytial virus recognize the viral nucleoprotein (N), but not the major glycoprotein (G), expressed by vaccinia virus recombinants. Journal of Immunology 137:3973–3977
    [Google Scholar]
  3. Blaney J. E. Jr, Nobusawa E., Brehm M. A., Bonneau R. H., Mylin L. M., Fu T. M., Kawaoka Y., Tevethia S. S. 1998; Immunization with a single major histocompatibility complex class I-restricted cytotoxic T-lymphocyte recognition epitope of herpes simplex virus type 2 confers protective immunity. Journal of Virology 72:9567–9574
    [Google Scholar]
  4. 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. Journal of Virology 66:2102–2110
    [Google Scholar]
  5. Collins P. L., Huang Y. T., Wertz G. W. 1984; Nucleotide sequence of the gene encoding the fusion (F) glycoprotein of human respiratory syncytial virus. Proceedings of the National Academy of Sciences, USA 81:7683–7687
    [Google Scholar]
  6. Collins P. L., McIntosh K., Chanock R. M. 1996; Respiratory syncytial virus. In Fields Virology pp 1313–1351 Edited by Fields B. N., Knipe D. M., Howley P. M. Philadelphia: Lippincott–Raven;
    [Google Scholar]
  7. Connors M., Giese N. A., Kulkarni A. B., Firestone C. Y., Morse H. C., Murphy B. R. 1994; Enhanced pulmonary histopathology induced by respiratory syncytial virus (RSV) challenge of formalin-inactivated RSV-immunized BALB/c mice is abrogated by depletion of interleukin-4 (IL-4) and IL-10. Journal of Virology 68:5321–5325
    [Google Scholar]
  8. Engelhard V. H. 1994; Structure of peptides associated with class I and class II. MHC molecules Annual Review of Immunology 12:181–207
    [Google Scholar]
  9. Enssle K. H., Fleischer B. 1990; Absence of Epstein–Barr virus-specific, HLA class II-restricted CD4+ cytotoxic T lymphocytes in infectious mononucleosis. Clinical and Experimental Immunology 79:409–415
    [Google Scholar]
  10. Falk K., Rotzschke O., Rammensee H. G. 1990; Cellular peptide composition governed by major histocompatibility complex class I molecules. Nature 348:248–251
    [Google Scholar]
  11. Falk K., Rotzschke O., Stevanovic S., Jung G., Rammensee H. G. 1991; Allele-specific motifs revealed by sequencing of self-peptides eluted from MHC molecules. Nature 351:290–296
    [Google Scholar]
  12. Feltkamp M. C., Smits H. L., Vierboom M. P., Minnaar R. P., de Jongh B. M., Drijfhout J. W., ter Schegget J., Melief C. J., Kast W. M. 1993; Vaccination with cytotoxic T lymphocyte epitope-containing peptide protects against a tumor induced by human papillomavirus type 16-transformed cells. European Journal of Immunology 23:2242–2249
    [Google Scholar]
  13. Fremont D. H., Matsumura M., Stura E. A., Peterson P. A., Wilson I. A. 1992; Crystal structures of two viral peptides in complex with murine MHC class I H-2Kb. Science 257:919–927
    [Google Scholar]
  14. Fung-Leung W. P., Kundig T. M., Zinkernagel R. M., Mak T. W. 1991; Immune response against lymphocytic choriomeningitis virus infection in mice without CD8 expression. Journal of Experimental Medicine 174:1425–1429
    [Google Scholar]
  15. Gao G. F., Willcox B. E., Wyer J. R., Boulter J. M., O’Callaghan C. A., Maenaka K., Stuart D. I., Jones E. Y., Van Der Merwe P. A., Bell J. I., Jakobsen B. K. 2000; Classical and nonclassical class I major histocompatibility complex molecules exhibit subtle conformational differences that affect binding to CD8αα. Journal of Biological Chemistry 275:15232–15238
    [Google Scholar]
  16. Garboczi D. N., Hung D. T., Wiley D. C. 1992; HLA-A2–peptide complexes: refolding and crystallization of molecules expressed in Escherichia coli and complexed with single antigenic peptides. Proceedings of the National Academy of Sciences, USA 89:3429–3433
    [Google Scholar]
  17. Graham B. S. 1996; Immunological determinants of disease caused by respiratory syncytial virus. Trends in Microbiology 4:290–293
    [Google Scholar]
  18. 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. Journal of Clinical Investigation 88:1026–1033
    [Google Scholar]
  19. Gromme M., Uytdehaag F. G., Janssen H., Calafat J., van Binnendijk R. S., Kenter M. J., Tulp A., Verwoerd D., Neefjes J. 1999; Recycling MHC class I molecules and endosomal peptide loading. Proceedings of the National Academy of Sciences, USA 96:10326–10331
    [Google Scholar]
  20. Horig H., Young A. C., Papadopoulos N. J., DiLorenzo T. P., Nathenson S. G. 1999; Binding of longer peptides to the H-2Kb heterodimer is restricted to peptides extended at their C terminus: refinement of the inherent MHC class I peptide binding criteria. Journal of Immunology 163:4434–4441
    [Google Scholar]
  21. Hsu S. C., Obeid O. E., Collins M., Iqbal M., Chargelegue D., Steward M. W. 1998; Protective cytotoxic T lymphocyte responses against paramyxoviruses induced by epitope-based DNA vaccines: involvement of IFN-gamma. International Immunology 10:1441–1447
    [Google Scholar]
  22. Hsu S. C., Chargelegue D., Obeid O. E., Steward M. W. 1999; Synergistic effect of immunization with a peptide cocktail inducing antibody, helper and cytotoxic T-cell responses on protection against respiratory syncytial virus. Journal of General Virology 80:1401–1405
    [Google Scholar]
  23. Kast W. M., Brandt R. M., Drijfhout J. W., Melief C. J. 1993; Human leukocyte antigen-A2.1 restricted candidate cytotoxic T lymphocyte epitopes of human papillomavirus type 16 E6 and E7 proteins identified by using the processing-defective human cell line T2. Journal of Immunotherapy 14:115–120
    [Google Scholar]
  24. Kast W. M., Brandt R. M., Sidney J., Drijfhout J. W., Kubo R. T., Grey H. M., Melief C. J., Sette A. 1994; Role of HLA-A motifs in identification of potential CTL epitopes in human papillomavirus type 16 E6 and E7 proteins. Journal of Immunology 152:3904–3912
    [Google Scholar]
  25. Kim H., Canchola J. G., Brandt C. D., Chanock R. M., Jensen K., Parrott R. H. 1969; Respiratory syncytial virus disease in infants despite prior administration of antigenic inactivated vaccine. American Journal of Epidemiology 89:422–434
    [Google Scholar]
  26. Kulkarni A. B., Connors M., Firestone C. Y., Morse H. C., Murphy B. R. 1993; The cytolytic activity of pulmonary CD8+ lymphocytes, induced by infection with a vaccinia virus recombinant expressing the M2 protein of respiratory syncytial virus (RSV), correlates with resistance to RSV infection in mice. Journal of Virology 67:1044–1049
    [Google Scholar]
  27. Lipford G. B., Hoffman M., Wagner H., Heeg K. 1993; Primary in vivo responses to ovalbumin. Probing the predictive value of the Kb binding motif. Journal of Immunology 150:1212–1222
    [Google Scholar]
  28. Madden D. R., Garboczi D. N., Wiley D. C. 1993; The antigenic identity of peptide–MHC complexes: a comparison of the conformations of five viral peptides presented by HLA-A2. Cell 75:693–708
    [Google Scholar]
  29. Moskophidis D., Assmann W. U., Simon M. M., Lehmann G. F. 1987; The immune response of the mouse to lymphocytic choriomeningitis virus. V. High numbers of cytolytic T lymphocytes are generated in the spleen during acute infection. European Journal of Immunology 17:937–942
    [Google Scholar]
  30. Nicholas J. A., Rubino K. L., Levely M. E., Adams E. G., Collins P. L. 1990; Cytolytic T-lymphocyte responses to respiratory syncytial virus: effector cell phenotype and target proteins. Journal of Virology 64:4232–4241
    [Google Scholar]
  31. Niedermann G., King G., Butz S., Birsner U., Grimm R., Shabanowitz J., Hunt D. F., Eichmann K. 1996; The proteolytic fragments generated by vertebrate proteasomes: structural relationships to major histocompatibility complex class I binding peptides. Proceedings of the National Academy of Sciences, USA 93:8572–8577
    [Google Scholar]
  32. Openshaw P. J., Clarke S. L., Record F. M. 1992; Pulmonary eosinophilic response to respiratory syncytial virus infection in mice sensitized to the major surface glycoprotein G. International. Immunology4493–500
    [Google Scholar]
  33. Pamer E. G., Harty J. T., Bevan M. J. 1991; Precise prediction of a dominant class I MHC-restricted epitope of Listeria monocytogenes. Nature 353:852–855
    [Google Scholar]
  34. Partidos C. D., Vohra P., Steward M. W. 1996; Induction of measles virus-specific cytotoxic T-cell responses after intranasal immunization with synthetic peptides. Immunology 87:179–185
    [Google Scholar]
  35. Pemberton R. M., Cannon M. J., Openshaw P. J., Ball L. A., Wertz G. W., Askonas B. A. 1987; Cytotoxic T cell specificity for respiratory syncytial virus proteins: fusion protein is an important target antigen. Journal of General Virology 68:2177–2182
    [Google Scholar]
  36. Srikiatkhachorn A., Braciale T. J. 1997; Virus-specific CD8+ T lymphocytes downregulate T helper cell type 2 cytokine secretion and pulmonary eosinophilia during experimental murine respiratory syncytial virus infection. Journal of Experimental Medicine 186:421–432
    [Google Scholar]
  37. Stryhn A., Pederson L. O., Holm A., Buus S. 2000; Longer peptides an be accommodated in the MHC binding site by a protrusion mechanism. European Journal of Immunology 30:3089–3099
    [Google Scholar]
  38. Taylor G., Stott E. J., Hayle A. J. 1985; Cytotoxic lymphocytes in the lungs of mice infected with respiratory syncytial virus. Journal of General Virology 66:2533–2538
    [Google Scholar]
  39. Urban R. G., Chicz R. M., Lane W. S., Strominger J. L., Rehm A., Kenter M. J., Uytdehaag F. G., Ploegh H., Uchanska Z. B., Ziegler A. 1994; A subset of HLA-B27 molecules contains peptides much longer than nonamers. Proceedings of the National Academy of Sciences, USA 91:1534–1538
    [Google Scholar]
  40. Waris M. E., Tsou C., Erdman D. D., Day D. B., Anderson L. J. 1997; Priming with live respiratory syncytial virus (RSV) prevents the enhanced pulmonary inflammatory response seen after RSV challenge in BALB/c mice immunized with formalin-inactivated RSV. Journal of Virology 71:6935–6939
    [Google Scholar]
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