1887

Abstract

The immunogenicity of chimeric peptides produced by collinear synthesis to contain both T and B cell epitopes from the fusion protein and the haemagglutinin of measles virus was studied in mice. The T cell epitope used was from the fusion protein (residues 288 to 302), which has been shown to be promiscuous in its binding to mouse major histocompatibility complex molecules. This epitope was coupled by (i) a glycine-glycine spacer to a B cell epitope from the fusion protein (residues 404 to 414) and (ii) either its amino or carboxy terminus to a neutralizing antibody epitope from the haemagglutinin (residues 188 to 199). The results obtained show that such chimeric peptides can indeed function as complete immunogens in a range of mouse strains of different H-2 haplotype, and can induce the production of antibodies which bind to the fusion protein and to measles virus. Furthermore, it was shown that the orientation of the T cell epitope with respect to the B cell epitope had a significant effect upon the immunogenicity and antigenic specificity of the chimera. This work gives further support to the concept of rationally designed synthetic peptide vaccines.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/0022-1317-72-6-1293
1991-06-01
2024-12-04
Loading full text...

Full text loading...

/deliver/fulltext/jgv/72/6/JV0720061293.html?itemId=/content/journal/jgv/10.1099/0022-1317-72-6-1293&mimeType=html&fmt=ahah

References

  1. Berzofsky J. A. 1987; Ir Genes: antigen-specific genetic regulation of the immune response. The Antigens 7:1–113
    [Google Scholar]
  2. Cease K., Margalit H., Cornette J., Putney S., Robey W., Ouyang C., Streicher H., Fischinger P. J., Gallo R. C., DeLisi C., Berzofsky J. A. 1987; Helper T cell antigenic site identification in the acquired immunodeficiency syndrome virus gpl20 envelope protein and induction of immunity in mice to the native protein using a 16-residue synthetic peptide. Proceedings of the National Academy of Sciences, U.S.A 84:4249–4253
    [Google Scholar]
  3. Cox J. H., Ivanyi J., Young D. B., Lamb J. R., Syred A. D., Francis M. J. 1988; Orientation of epitopes influences the immunogenicity of synthetic peptide dimers. European Journal of Immunology 18:2015–2019
    [Google Scholar]
  4. DeLisi C., Berzofsky J. A. 1985; T cell antigenic sites tend to be amphipathic structures. Proceedings of the National Academy of Sciences, U.S.A 82:7048–7053
    [Google Scholar]
  5. Francis M. J., Hastings G. Z., Syred A. D., McGinn B., Brown F., Rowlands D. J. 1988; Peptides with added T-cell epitopes can overcome genetic restriction of the immune response. In Vaccines’88, New Chemical and Genetic Approaches to Vaccination pp 1–7 Edited by Ginsberg H., Brown F., Lerner R. A., Chanock R. M. New York: Cold Spring Harbor Laboratory;
    [Google Scholar]
  6. Hale P. M., Cease K. B., Houghten R. A., Ouyang C., Putney S., Javaherian K., Margalit H., Cornette J. L., Spouge J. L., DeLisi C., Berzofsky J. A. 1989; T-cell multideterminant regions in the human immunodeficiency virus envelope: towards overcoming the problem of major histocompatibility complex restriction. International Immunology 1:409–415
    [Google Scholar]
  7. Hedrick S. M. 1988; Specificity of the T cell receptor for antigen. Advances in Immunology 43:193–234
    [Google Scholar]
  8. Holland G. P., Holland N., Steward M. W. 1990; Interferon-gamma potentiates antibody affinity in mice with a genetically controlled defect in affinity maturation. Clinical and Experimental Immunology 82:221–226
    [Google Scholar]
  9. Hull J., Krah D., Choppin P. 1987; Resistance of measles virus mutant to fusion inhibiting oligopeptides is not associated with mutations in the fusion peptide. Virology 159:368–372
    [Google Scholar]
  10. Karplus P. A., Schultz G. E. 1985; Prediction of chain flexibility in proteins. A tool for the selection of peptide antigens. Naturwissens-chaften 72:212–213
    [Google Scholar]
  11. Kilgus J., Jardetzky T., Gorga J. C., Trzeciak A., Gillessen D., Sinigaglia F. 1991; Analysis of the permissive association of a malaria T cell epitope with DR molecules. Journal of Immunology 146:307–315
    [Google Scholar]
  12. Kyte J., Doolittle R. F. 1982; A simple method for displaying the hydropathic character of a protein. Journal of Molecular Biology 157:105–132
    [Google Scholar]
  13. Lamb J. R., Ivanyi J., Rees A. D. M., Rothbard J. B., Howland K., Young R. A., Young D. B. 1987; Mapping of T cell epitopes using recombinant antigens and synthetic peptides. EMBO Journal 6:1245–1249
    [Google Scholar]
  14. Lamb J. R., Rees A. D. M., Bal V., Ikeda H., Wilkinson D., DeVries R. R. P., Rothbard J. B. 1988; Prediction and identification of an HLA-DR restricted T cell determinant in the 19-KD protein of Mycobacterium tuberculosis . European Journal of Immunology 18:973–976
    [Google Scholar]
  15. Mӓkelӓ M. J., Lund G. A., Salmi A. A. 1989; Antigenicity of the measles virus haemagglutinin studied by using synthetic peptides. Journal of General Virology 70:603–614
    [Google Scholar]
  16. Margalit H., Spouge J. L., Cornette J. L., Cease K. B., DeLisi C., Berzofsky J. A. 1987; Prediction of immunodominant helper T cell antigenic sites from the primary sequence. Journal of Immunology 138:2213–2229
    [Google Scholar]
  17. Merz D. C., Scheid A., Choppin P. W. 1980; The importance of antibody to fusion protein (F) of paramyxoviruses in the prevention of spread of infection. Journal of Experimental Medicine 151:275–288
    [Google Scholar]
  18. Milich D. R. 1989; Synthetic T and B cell recognition sites: implications for vaccine development. Advances in Immunology 45:195–264
    [Google Scholar]
  19. Norrby E., Enders-Ruckle G., Ter Meulen V. 1975; Differences in the appearance of antibodies to structural components of measles virus after immunization with inactivated and live virus. Journal of Infectious Diseases 132:262–269
    [Google Scholar]
  20. Panina-Bordignon P., Tan A., Termijtelen A., Demotz S., Corradin G. P., Lanzavecchia A. 1989; Universally immunogenic T cell epitopes: promiscuous binding to human class II and promiscuous recognition by T cells. European Journal of Immunology 19:2237–2242
    [Google Scholar]
  21. Partidos C. D., Steward M. W. 1990; Prediction and identification of a T cell epitope in the fusion protein of measles virus immunodominant in mice and humans. Journal of General Virology 71:2099–2105
    [Google Scholar]
  22. Portner A., Scroggs R., Naeve C. 1987; The fusion glycoprotein of Sendai virus: sequence analysis of an epitope involved in fusion and virus neutralization. Virology 157:556–559
    [Google Scholar]
  23. Richardson C., Hull D., Greer P., Hasel K., Berkovich A., England D., Bellini W., Rima B., Lazzarini R. 1986; The nucleotide sequence of the mRNA encoding the fusion protein of measles virus (Edmonston strain): a comparison of fusion proteins from several paramyxoviruses. Virology 155:508–523
    [Google Scholar]
  24. Rothbard J., Taylor W. 1988; A sequence pattern common to T cell epitopes. EMBO Journal 7:93–101
    [Google Scholar]
  25. Rothbard J., Lechler R. I., Howland K., Bal V., Eckels D. D., Sekaly R., Long E. O., Taylor W. R., Lamb J. R. 1988; Structural model of HLA-DR restricted T cell antigen recognition. Cell 52:515–523
    [Google Scholar]
  26. Sette A., Buus S., Appella E., Smith J. A., Chestnut R., Miles C., Colon S. M., Grey H. M. 1989; Prediction of major histocompatibility complex binding regions of protein antigens by sequence pattern analysis. Proceedings of the National Academy of Science, U.S.A 86:3296–3300
    [Google Scholar]
  27. Sinigaglia F., Guttinger M., Kilgus J., Doran D. M., Matile H., Etlinger H., Trzeciak A., Gillessen O., Pink J. R. L. 1988; A malaria T cell epitope recognised in association with most mouse and human class II molecules. Nature, London 336:778–780
    [Google Scholar]
  28. Spouge J., Guy H., Cornette J., Margalit H., Cease K., Berzofsky I., DeLisi C. 1987; Strong conformational propensities enhance T cell antigenicity. Journal of Immunology 138:204–212
    [Google Scholar]
  29. Steward M. W., Howard C. 1987; Synthetic peptides: a next generation of vaccines?. Immunology Today 8:51–58
    [Google Scholar]
  30. Steward M. W., Steensgaard J. 1983; The biological significance of antibody affinity. Antibody Affinity: Thermodynamic Aspects and Biological Significance Boca Raton: CRC Press;
    [Google Scholar]
  31. Thornton J. M., Edwards M. S., Taylor W. R., Barlow D. J. 1986; Localization of continuous antigenic determinants in the protruding regions of proteins. EMBO Journal 5:409–413
    [Google Scholar]
  32. Varsanyi T. M., Utter G., Norrby E. 1984; Purification, morphology and antigenic characterization of measles virus envelope components. Journal of General Virology 65:355–366
    [Google Scholar]
  33. Wilmot C. M., Thornton J. M. 1988; Analysis and prediction of different types of β-turns in proteins. Journal of Molecular Biology 203:221–232
    [Google Scholar]
/content/journal/jgv/10.1099/0022-1317-72-6-1293
Loading
/content/journal/jgv/10.1099/0022-1317-72-6-1293
Loading

Data & Media loading...

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