Skip to main content
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1988 Nov 1;168(5):1855–1864. doi: 10.1084/jem.168.5.1855

MHC-restricted recognition of immunogenic T cell epitopes of pertussis toxin reveals determinants in man distinct from the ADP-ribosylase active site

PMCID: PMC2189123  PMID: 2460578

Abstract

The S1 subunit of Pertussis toxin (PT) is responsible for the reactogenicity and in part the immunogenicity of Bordetella pertussis vaccine. The critical residues associated with the immunomodulatory effects of PT were located around Glu140 in the S1 subunit. In man, T cell responses to PT are directed at S1 peptides distinct from Glu140. Two such epitopes, p64-75 and p151-161, are immunogenic in a panel of individuals covering a wide range of HLA genotypes. The response to PT peptides is HLA class II restricted. The response to p64-75 is blocked by an anti-HLA-DQ mAb, while that to p151-161 is blocked by an anti-HLA- DR mAb. These findings may allow for the development of a B. pertussis vaccine free from reactogenicity.

Full Text

The Full Text of this article is available as a PDF (768.7 KB).

Selected References

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

  1. Ada G. L., Jones P. D. Vaccines for the future--an update. Immunol Cell Biol. 1987 Feb;65(Pt 1):11–24. doi: 10.1038/icb.1987.2. [DOI] [PubMed] [Google Scholar]
  2. Askelöf P., Rodmalm K., Abens J., Undén A., Bartfai T. Use of synthetic peptides to map antigenic sites of Bordetella pertussis toxin subunit S1. J Infect Dis. 1988 Apr;157(4):738–742. doi: 10.1093/infdis/157.4.738. [DOI] [PubMed] [Google Scholar]
  3. Babbitt B. P., Allen P. M., Matsueda G., Haber E., Unanue E. R. Binding of immunogenic peptides to Ia histocompatibility molecules. 1985 Sep 26-Oct 2Nature. 317(6035):359–361. doi: 10.1038/317359a0. [DOI] [PubMed] [Google Scholar]
  4. Banerjee S., Haqqi T. M., Luthra H. S., Stuart J. M., David C. S. Possible role of V beta T cell receptor genes in susceptibility to collagen-induced arthritis in mice. J Exp Med. 1988 Mar 1;167(3):832–839. doi: 10.1084/jem.167.3.832. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Black W. J., Munoz J. J., Peacock M. G., Schad P. A., Cowell J. L., Burchall J. J., Lim M., Kent A., Steinman L., Falkow S. ADP-ribosyltransferase activity of pertussis toxin and immunomodulation by Bordetella pertussis. Science. 1988 Apr 29;240(4852):656–659. doi: 10.1126/science.2896387. [DOI] [PubMed] [Google Scholar]
  6. 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]
  7. Cody C. L., Baraff L. J., Cherry J. D., Marcy S. M., Manclark C. R. Nature and rates of adverse reactions associated with DTP and DT immunizations in infants and children. Pediatrics. 1981 Nov;68(5):650–660. [PubMed] [Google Scholar]
  8. 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]
  9. Fine P. E., Clarkson J. A. Individual versus public priorities in the determination of optimal vaccination policies. Am J Epidemiol. 1986 Dec;124(6):1012–1020. doi: 10.1093/oxfordjournals.aje.a114471. [DOI] [PubMed] [Google Scholar]
  10. Freundlich B., Avdalovic N. Use of gelatin/plasma coated flasks for isolating human peripheral blood monocytes. J Immunol Methods. 1983 Aug 12;62(1):31–37. doi: 10.1016/0022-1759(83)90107-2. [DOI] [PubMed] [Google Scholar]
  11. Good M. F., Maloy W. L., Lunde M. N., Margalit H., Cornette J. L., Smith G. L., Moss B., Miller L. H., Berzofsky J. A. Construction of synthetic immunogen: use of new T-helper epitope on malaria circumsporozoite protein. Science. 1987 Feb 27;235(4792):1059–1062. doi: 10.1126/science.2434994. [DOI] [PubMed] [Google Scholar]
  12. Heber-Katz E., Valentine S., Dietzschold B., Burns-Purzycki C. Overlapping T cell antigenic sites on a synthetic peptide fragment from herpes simplex virus glycoprotein D, the degenerate MHC restriction elicited, and functional evidence for antigen-Ia interaction. J Exp Med. 1988 Feb 1;167(2):275–287. doi: 10.1084/jem.167.2.275. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. 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]
  14. Janeway C. A., Paul W. E. The specificity of cellular immune responses in guinea pigs. III. The precision of antigen recognition by T lymphocytes. J Exp Med. 1976 Dec 1;144(6):1641–1656. doi: 10.1084/jem.144.6.1641. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. KENDRICK P. L., UPDYKE E. L., ELDERING G. Comparison of pertussis cultures by mouse protection and virulence tests . Am J Public Health Nations Health. 1949 Feb;39(2):179–184. doi: 10.2105/ajph.39.2.179. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Kendrick P. L., Eldering G., Dixon M. K., Misner J. Mouse Protection Tests in the Study of Pertussis Vaccine: A Comparative Series Using the Intracerebral Route for Challenge. Am J Public Health Nations Health. 1947 Jul;37(7):803–810. [PMC free article] [PubMed] [Google Scholar]
  17. Locht C., Keith J. M. Pertussis toxin gene: nucleotide sequence and genetic organization. Science. 1986 Jun 6;232(4755):1258–1264. doi: 10.1126/science.3704651. [DOI] [PubMed] [Google Scholar]
  18. Manca F., Kunkl A., Fenoglio D., Fowler A., Sercarz E., Celada F. Constraints in T-B cooperation related to epitope topology on E. coli beta-galactosidase. I. The fine specificity of T cells dictates the fine specificity of antibodies directed to conformation-dependent determinants. Eur J Immunol. 1985 Apr;15(4):345–350. doi: 10.1002/eji.1830150408. [DOI] [PubMed] [Google Scholar]
  19. Miller D. L., Ross E. M., Alderslade R., Bellman M. H., Rawson N. S. Pertussis immunisation and serious acute neurological illness in children. Br Med J (Clin Res Ed) 1981 May 16;282(6276):1595–1599. doi: 10.1136/bmj.282.6276.1595. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Nicosia A., Bartoloni A., Perugini M., Rappuoli R. Expression and immunological properties of the five subunits of pertussis toxin. Infect Immun. 1987 Apr;55(4):963–967. doi: 10.1128/iai.55.4.963-967.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Nicosia A., Perugini M., Franzini C., Casagli M. C., Borri M. G., Antoni G., Almoni M., Neri P., Ratti G., Rappuoli R. Cloning and sequencing of the pertussis toxin genes: operon structure and gene duplication. Proc Natl Acad Sci U S A. 1986 Jul;83(13):4631–4635. doi: 10.1073/pnas.83.13.4631. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Oksenberg J. R., Mor-Yosef S., Persitz E., Schenker Y., Mozes E., Brautbar C. Antigen-presenting cells in human decidual tissue. Am J Reprod Immunol Microbiol. 1986 Jul;11(3):82–88. doi: 10.1111/j.1600-0897.1986.tb00036.x. [DOI] [PubMed] [Google Scholar]
  23. Oldstone M. B. Molecular mimicry and autoimmune disease. Cell. 1987 Sep 11;50(6):819–820. doi: 10.1016/0092-8674(87)90507-1. [DOI] [PubMed] [Google Scholar]
  24. Sasazuki T., Nishimura Y., Muto M., Ohta N. HLA-linked genes controlling immune response and disease susceptibility. Immunol Rev. 1983;70:51–75. doi: 10.1111/j.1600-065x.1983.tb00709.x. [DOI] [PubMed] [Google Scholar]
  25. Sato H., Sato Y. Bordetella pertussis infection in mice: correlation of specific antibodies against two antigens, pertussis toxin, and filamentous hemagglutinin with mouse protectivity in an intracerebral or aerosol challenge system. Infect Immun. 1984 Nov;46(2):415–421. doi: 10.1128/iai.46.2.415-421.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Sato Y., Kimura M., Fukumi H. Development of a pertussis component vaccine in Japan. Lancet. 1984 Jan 21;1(8369):122–126. doi: 10.1016/s0140-6736(84)90061-8. [DOI] [PubMed] [Google Scholar]
  27. Steinman L., Weiss A., Adelman N., Lim M., Zuniga R., Oehlert J., Hewlett E., Falkow S. Pertussis toxin is required for pertussis vaccine encephalopathy. Proc Natl Acad Sci U S A. 1985 Dec;82(24):8733–8736. doi: 10.1073/pnas.82.24.8733. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Tainer J. A., Getzoff E. D., Paterson Y., Olson A. J., Lerner R. A. The atomic mobility component of protein antigenicity. Annu Rev Immunol. 1985;3:501–535. doi: 10.1146/annurev.iy.03.040185.002441. [DOI] [PubMed] [Google Scholar]
  29. Taub R. N., Rosett W., Adler A., Morse S. I. Distribution of labeled lymph node cells in mice during the lymphocytosis induced by Bordetella pertussis. J Exp Med. 1972 Dec 1;136(6):1581–1593. doi: 10.1084/jem.136.6.1581. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Vogel F. R., Leclerc C., Schutze M. P., Jolivet M., Audibert F., Klein T. W., Chedid L. Modulation of carrier-induced epitopic suppression by Bordetella pertussis components and muramyl peptide. Cell Immunol. 1987 Jun;107(1):40–51. doi: 10.1016/0008-8749(87)90264-4. [DOI] [PubMed] [Google Scholar]
  31. Wardlaw A. C., Parton R. Bordetella pertussis toxins. Pharmacol Ther. 1982;19(1):1–53. doi: 10.1016/0163-7258(82)90041-9. [DOI] [PubMed] [Google Scholar]
  32. Yajima M., Hosoda K., Kanbayashi Y., Nakamura T., Nogimori K., Mizushima Y., Nakase Y., Ui M. Islets-activating protein (IAP) in Bordetella pertussis that potentiates insulin secretory responses of rats. Purification and characterization. J Biochem. 1978 Jan;83(1):295–303. doi: 10.1093/oxfordjournals.jbchem.a131904. [DOI] [PubMed] [Google Scholar]
  33. Zamvil S. S., Mitchell D. J., Moore A. C., Kitamura K., Steinman L., Rothbard J. B. T-cell epitope of the autoantigen myelin basic protein that induces encephalomyelitis. Nature. 1986 Nov 20;324(6094):258–260. doi: 10.1038/324258a0. [DOI] [PubMed] [Google Scholar]
  34. de Vries R. P., Kreeftenberg H. G., Loggen H. G., van Rood J. J. In vitro immune responsiveness to vaccinea virus and HLA. N Engl J Med. 1977 Sep 29;297(13):692–696. doi: 10.1056/NEJM197709292971303. [DOI] [PubMed] [Google Scholar]

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

RESOURCES