Skip to main content
NCBI home page
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1986 Aug 1;164(2):532–547. doi: 10.1084/jem.164.2.532

Nonoverlapping T and B cell determinants on an hepatitis B surface antigen pre-S(2) region synthetic peptide

PMCID: PMC2188234  PMID: 2425034

Abstract

We have examined T cell recognition of a hepatitis B surface antigen (HBsAg), pre-S(2)-region synthetic peptide, p120-145, in terms of fine specificity, H-2-linked genetic influences, comparison to antibody binding, and relevance to T cell recognition of the native protein. We showed that the immune response to the synthetic peptide is regulated by H-2-linked genes, but that the pattern of H-2 restriction differed from that observed for the native anti-pre-S(2) response. Dominant and nonoverlapping T cell and B cell recognition sites were identified on the synthetic peptide p120-145. T cell recognition is focussed on the NH2-terminal sequence, and antibody (B cell) recognition is focussed on the COOH-terminal sequence. The fine specificity of T cell recognition of p120-145 was defined by a single, subtype-dependent amino acid substitution. With respect to the immunogenicity of p120-145, the synthetic peptide containing both T and B cell determinants is highly immunogenic in responder strains, whereas separate T or B cell peptide determinants are minimally immunogenic. Furthermore, the synthetic T cell recognition site can prime T cell help for antibody production to the synthetic B cell site, which is crossreactive with the native pre- S(2) region of HBsAg/p33 particles. This system provides evidence that totally synthetic T cell and B cell recognition sites can be combined to yield a functional immunogen.

Full Text

The Full Text of this article is available as a PDF (982.8 KB).

Selected References

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

  1. Click R. E., Benck L., Alter B. J. Immune responses in vitro. I. Culture conditions for antibody synthesis. Cell Immunol. 1972 Feb;3(2):264–276. doi: 10.1016/0008-8749(72)90165-7. [DOI] [PubMed] [Google Scholar]
  2. DeLisi C., Berzofsky J. A. T-cell antigenic sites tend to be amphipathic structures. Proc Natl Acad Sci U S A. 1985 Oct;82(20):7048–7052. doi: 10.1073/pnas.82.20.7048. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Heber-Katz E., Hansburg D., Schwartz R. H. The Ia molecule of the antigen-presenting cell plays a critical role in immune response gene regulation of T cell activation. J Mol Cell Immunol. 1983;1(1):3–18. [PubMed] [Google Scholar]
  4. Heermann K. H., Goldmann U., Schwartz W., Seyffarth T., Baumgarten H., Gerlich W. H. Large surface proteins of hepatitis B virus containing the pre-s sequence. J Virol. 1984 Nov;52(2):396–402. doi: 10.1128/jvi.52.2.396-402.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Machida A., Kishimoto S., Ohnuma H., Baba K., Ito Y., Miyamoto H., Funatsu G., Oda K., Usuda S., Togami S. A polypeptide containing 55 amino acid residues coded by the pre-S region of hepatitis B virus deoxyribonucleic acid bears the receptor for polymerized human as well as chimpanzee albumins. Gastroenterology. 1984 May;86(5 Pt 1):910–918. [PubMed] [Google Scholar]
  6. Michel M. L., Pontisso P., Sobczak E., Malpièce Y., Streeck R. E., Tiollais P. Synthesis in animal cells of hepatitis B surface antigen particles carrying a receptor for polymerized human serum albumin. Proc Natl Acad Sci U S A. 1984 Dec;81(24):7708–7712. doi: 10.1073/pnas.81.24.7708. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Milich D. R., Chisari F. V. Genetic regulation of the immune response to hepatitis B surface antigen (HBsAg). I. H-2 restriction of the murine humoral immune response to the a and d determinants of HBsAg. J Immunol. 1982 Jul;129(1):320–325. [PubMed] [Google Scholar]
  8. Milich D. R., Leroux-Roels G. G., Louie R. E., Chisari F. V. Genetic regulation of the immune response to hepatitis B surface antigen (HBsAg). IV. Distinct H-2-linked Ir genes control antibody responses to different HBsAg determinants on the same molecule and map to the I-A and I-C subregions. J Exp Med. 1984 Jan 1;159(1):41–56. doi: 10.1084/jem.159.1.41. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Milich D. R., Louie R. E., Chisari F. V. Genetic regulation of the immune response to hepatitis B surface antigen (HBsAg). V. T cell proliferative response and cellular interactions. J Immunol. 1985 Jun;134(6):4194–4202. [PubMed] [Google Scholar]
  10. Milich D. R., McNamara M. K., McLachlan A., Thornton G. B., Chisari F. V. Distinct H-2-linked regulation of T-cell responses to the pre-S and S regions of the same hepatitis B surface antigen polypeptide allows circumvention of nonresponsiveness to the S region. Proc Natl Acad Sci U S A. 1985 Dec;82(23):8168–8172. doi: 10.1073/pnas.82.23.8168. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Milich D. R., Peterson D. L., Leroux-Roels G. G., Lerner R. A., Chisari F. V. Genetic regulation of the immune response to hepatitis B surface antigen (HBsAg). VI. T cell fine specificity. J Immunol. 1985 Jun;134(6):4203–4211. [PubMed] [Google Scholar]
  12. Milich D. R., Thornton G. B., Neurath A. R., Kent S. B., Michel M. L., Tiollais P., Chisari F. V. Enhanced immunogenicity of the pre-S region of hepatitis B surface antigen. Science. 1985 Jun 7;228(4704):1195–1199. doi: 10.1126/science.2408336. [DOI] [PubMed] [Google Scholar]
  13. Neurath A. R., Kent S. B., Strick N. Location and chemical synthesis of a pre-S gene coded immunodominant epitope of hepatitis B virus. Science. 1984 Apr 27;224(4647):392–395. doi: 10.1126/science.6200931. [DOI] [PubMed] [Google Scholar]
  14. 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]
  15. Ono Y., Onda H., Sasada R., Igarashi K., Sugino Y., Nishioka K. The complete nucleotide sequences of the cloned hepatitis B virus DNA; subtype adr and adw. Nucleic Acids Res. 1983 Mar 25;11(6):1747–1757. doi: 10.1093/nar/11.6.1747. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Pasek M., Goto T., Gilbert W., Zink B., Schaller H., MacKay P., Leadbetter G., Murray K. Hepatitis B virus genes and their expression in E. coli. Nature. 1979 Dec 6;282(5739):575–579. doi: 10.1038/282575a0. [DOI] [PubMed] [Google Scholar]
  17. Pincus M. R., Gerewitz F., Schwartz R. H., Scheraga H. A. Correlation between the conformation of cytochrome c peptides and their stimulatory activity in a T-lymphocyte proliferation assay. Proc Natl Acad Sci U S A. 1983 Jun;80(11):3297–3300. doi: 10.1073/pnas.80.11.3297. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Rock K. L., Benacerraf B. Inhibition of antigen-specific T lymphocyte activation by structurally related Ir gene-controlled polymers. Evidence of specific competition for accessory cell antigen presentation. J Exp Med. 1983 May 1;157(5):1618–1634. doi: 10.1084/jem.157.5.1618. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Schwartz R. H., Fox B. S., Fraga E., Chen C., Singh B. The T lymphocyte response to cytochrome c. V. Determination of the minimal peptide size required for stimulation of T cell clones and assessment of the contribution of each residue beyond this size to antigenic potency. J Immunol. 1985 Oct;135(4):2598–2608. [PubMed] [Google Scholar]
  20. Schwartz R. H. T-lymphocyte recognition of antigen in association with gene products of the major histocompatibility complex. Annu Rev Immunol. 1985;3:237–261. doi: 10.1146/annurev.iy.03.040185.001321. [DOI] [PubMed] [Google Scholar]
  21. Shastri N., Miller A., Sercarz E. E. The expressed T cell repertoire is hierarchical: the precise focus of lysozyme-specific T cell clones is dependent upon the structure of the immunogen. J Mol Cell Immunol. 1984;1(6):369–379. [PubMed] [Google Scholar]
  22. Stibbe W., Gerlich W. H. Variable protein composition of hepatitis B surface antigen from different donors. Virology. 1982 Dec;123(2):436–442. doi: 10.1016/0042-6822(82)90275-6. [DOI] [PubMed] [Google Scholar]
  23. Valenzuela P., Gray P., Quiroga M., Zaldivar J., Goodman H. M., Rutter W. J. Nucleotide sequence of the gene coding for the major protein of hepatitis B virus surface antigen. Nature. 1979 Aug 30;280(5725):815–819. doi: 10.1038/280815a0. [DOI] [PubMed] [Google Scholar]
  24. Watts T. H., Gariépy J., Schoolnik G. K., McConnell H. M. T-cell activation by peptide antigen: effect of peptide sequence and method of antigen presentation. Proc Natl Acad Sci U S A. 1985 Aug;82(16):5480–5484. doi: 10.1073/pnas.82.16.5480. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Werdelin O. Chemically related antigens compete for presentation by accessory cells to T cells. J Immunol. 1982 Nov;129(5):1883–1891. [PubMed] [Google Scholar]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

RESOURCES