Skip to main content
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1990 Jul;87(14):5519–5522. doi: 10.1073/pnas.87.14.5519

Enhanced immunogenicity of a sequence derived from hepatitis B virus surface antigen in a composite peptide that includes the immunostimulatory region from human interleukin 1.

K V Rao 1, A R Nayak 1
PMCID: PMC54356  PMID: 2371286

Abstract

The effect on immunogenicity of coupling the immunostimulatory nonapeptide sequence (residues 163-171) from human interleukin 1 beta (IL-1 beta) to a small immunogen was examined. A 21-amino acid sequence spanning positions 12-32 on the large protein of hepatitis B surface antigen was chosen as a model. Three peptides were synthesized corresponding to the IL-1 beta-derived sequence [peptide IL-(163-171)], the hepatitis B surface antigen-derived sequence [peptide S1-(12-32)] and a composite peptide that included both these sequences separated by a spacer of two glycine residues [peptide S1-(12-32)-IL-(163-171)]. In an in vitro thymocyte proliferation assay, both peptides S1-(12-32)-IL-(163-171) and IL-(163-171) showed comparable activity, whereas peptide S1-(12-32) was inactive. Groups of five to seven mice each from C3H/CH, BALB/c, SJL/J, and C57BL/6 strains were immunized with equimolar amounts of either peptide S1-(12-32), peptide S1-(12-32)-IL-(163-171), or a mixture of peptides S1-(12-32) and IL-(163-171), and sera were screened for anti-S1-(12-32) antibodies. In all strains, peptide S1-(12-32)-IL-(163-171) elicited an increased primary and secondary anti-S1-(12-32) antibody response compared to the other two groups. Further, peptide S1-(12-32)-IL-(163-171) also induced an increased number of responders to primary immunization, though the number of responders was quantitative in all groups following secondary immunization. At least part of the enhanced immunogenicity of the S1-(12-32) sequence in peptide S1-(12-32)-IL-(163-171) appears to be due to augmented T-helper cell activity. These results suggest that coupling of the immunostimulatory IL-1 beta-derived sequence in tandem with an immunogen may confer inbuilt adjuvanticity.

Full text

PDF
5519

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Antoni G., Presentini R., Perin F., Tagliabue A., Ghiara P., Censini S., Volpini G., Villa L., Boraschi D. A short synthetic peptide fragment of human interleukin 1 with immunostimulatory but not inflammatory activity. J Immunol. 1986 Nov 15;137(10):3201–3204. [PubMed] [Google Scholar]
  2. Boraschi D., Volpini G., Villa L., Nencioni L., Scapigliati G., Nucci D., Antoni G., Matteucci G., Cioli F., Tagliabue A. A monoclonal antibody to the IL-1 beta peptide 163-171 blocks adjuvanticity but not pyrogenicity of IL-1 beta in vivo. J Immunol. 1989 Jul 1;143(1):131–134. [PubMed] [Google Scholar]
  3. Chou P. Y., Fasman G. D. Empirical predictions of protein conformation. Annu Rev Biochem. 1978;47:251–276. doi: 10.1146/annurev.bi.47.070178.001343. [DOI] [PubMed] [Google Scholar]
  4. Chou P. Y., Fasman G. D. Prediction of the secondary structure of proteins from their amino acid sequence. Adv Enzymol Relat Areas Mol Biol. 1978;47:45–148. doi: 10.1002/9780470122921.ch2. [DOI] [PubMed] [Google Scholar]
  5. Dinarello C. A. Interleukin-1 and its biologically related cytokines. Adv Immunol. 1989;44:153–205. doi: 10.1016/s0065-2776(08)60642-2. [DOI] [PubMed] [Google Scholar]
  6. Frasca D., Boraschi D., Baschieri S., Bossu P., Tagliabue A., Adorini L., Doria G. In vivo restoration of T cell functions by human IL-1 beta or its 163-171 nonapeptide in immunodepressed mice. J Immunol. 1988 Oct 15;141(8):2651–2655. [PubMed] [Google Scholar]
  7. Freedman A. S., Freeman G., Whitman J., Segil J., Daley J., Nadler L. M. Pre-exposure of human B cells to recombinant IL-1 enhances subsequent proliferation. J Immunol. 1988 Nov 15;141(10):3398–3404. [PubMed] [Google Scholar]
  8. Gery I., Gershon R. K., Waksman B. H. Potentiation of the T-lymphocyte response to mitogens. I. The responding cell. J Exp Med. 1972 Jul 1;136(1):128–142. doi: 10.1084/jem.136.1.128. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Hopp T. P., Woods K. R. Prediction of protein antigenic determinants from amino acid sequences. Proc Natl Acad Sci U S A. 1981 Jun;78(6):3824–3828. doi: 10.1073/pnas.78.6.3824. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. March C. J., Mosley B., Larsen A., Cerretti D. P., Braedt G., Price V., Gillis S., Henney C. S., Kronheim S. R., Grabstein K. Cloning, sequence and expression of two distinct human interleukin-1 complementary DNAs. Nature. 1985 Jun 20;315(6021):641–647. doi: 10.1038/315641a0. [DOI] [PubMed] [Google Scholar]
  11. Milich D. R., McLachlan A., Moriarty A., Thornton G. B. A single 10-residue pre-S(1) peptide can prime T cell help for antibody production to multiple epitopes within the pre-S(1), pre-S(2), and S regions of HBsAg. J Immunol. 1987 Jun 15;138(12):4457–4465. [PubMed] [Google Scholar]
  12. Milich D. R. T- and B-cell recognition of hepatitis B viral antigens. Immunol Today. 1988 Dec;9(12):380–386. doi: 10.1016/0167-5699(88)91239-X. [DOI] [PubMed] [Google Scholar]
  13. Mizel S. B., Ben-Zvi A. Studies on the role of lymphocyte-activating factor (Interleukin 1) in antigen-induced lymph node lymphocyte proliferation. Cell Immunol. 1980 Sep 1;54(2):382–389. doi: 10.1016/0008-8749(80)90218-x. [DOI] [PubMed] [Google Scholar]
  14. Nencioni L., Villa L., Tagliabue A., Antoni G., Presentini R., Perin F., Silvestri S., Boraschi D. In vivo immunostimulating activity of the 163-171 peptide of human IL-1 beta. J Immunol. 1987 Aug 1;139(3):800–804. [PubMed] [Google Scholar]
  15. Neurath A. R., Kent S. B., Parker K., Prince A. M., Strick N., Brotman B., Sproul P. Antibodies to a synthetic peptide from the preS 120-145 region of the hepatitis B virus envelope are virus neutralizing. Vaccine. 1986 Mar;4(1):35–37. doi: 10.1016/s0264-410x(86)80001-9. [DOI] [PubMed] [Google Scholar]
  16. Neurath A. R., Kent S. B., Strick N., Taylor P., Stevens C. E. Hepatitis B virus contains pre-S gene-encoded domains. Nature. 1985 May 9;315(6015):154–156. doi: 10.1038/315154a0. [DOI] [PubMed] [Google Scholar]
  17. Neurath A. R., Kent S. B. The pre-S region of hepadnavirus envelope proteins. Adv Virus Res. 1988;34:65–142. doi: 10.1016/s0065-3527(08)60516-3. [DOI] [PubMed] [Google Scholar]
  18. Pike B. L., Nossal G. J. Interleukin 1 can act as a B-cell growth and differentiation factor. Proc Natl Acad Sci U S A. 1985 Dec;82(23):8153–8157. doi: 10.1073/pnas.82.23.8153. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Reed S. G., Pihl D. L., Conlon P. J., Grabstein K. H. IL-1 as adjuvant. Role of T cells in the augmentation of specific antibody production by recombinant human IL-1 alpha. J Immunol. 1989 May 1;142(9):3129–3133. [PubMed] [Google Scholar]
  20. Reed S. G., Pihl D. L., Grabstein K. H. Immune deficiency in chronic Trypanosoma cruzi infection. Recombinant IL-1 restores Th function for antibody production. J Immunol. 1989 Mar 15;142(6):2067–2071. [PubMed] [Google Scholar]
  21. Tartakovsky B., Finnegan A., Muegge K., Brody D. T., Kovacs E. J., Smith M. R., Berzofsky J. A., Young H. A., Durum S. K. IL-1 is an autocrine growth factor for T cell clones. J Immunol. 1988 Dec 1;141(11):3863–3867. [PubMed] [Google Scholar]
  22. Uhl J., Newton R. C., Giri J. G., Sandlin G., Horuk R. Identification of IL-1 receptors on human monocytes. J Immunol. 1989 Mar 1;142(5):1576–1581. [PubMed] [Google Scholar]
  23. Wood D. D., Gaul S. L. Enhancement of the humoral response of T cell-depleted murine spleens by a factor derived from human monocytes in vitro. J Immunol. 1974 Sep;113(3):925–933. [PubMed] [Google Scholar]
  24. Yajima H., Minamitake Y., Funakoshi S., Katayama I., Fujii N., Segawa T., Nakata Y., Yasuhara T., Nakajima T. Studies on peptides. CVI: Synthesis of a physalaemin-like peptide, [Lys5, Thr6]-physalaemin, isolated from the skin of a frog, Uperoleia rugosa. Chem Pharm Bull (Tokyo) 1982 Jan;30(1):344–348. doi: 10.1248/cpb.30.344. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES