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. 1989 May 1;169(5):1519–1532. doi: 10.1084/jem.169.5.1519

Human T cell clones define S1 subunit as the most immunogenic moiety of pertussis toxin and determine its epitope map

PMCID: PMC2189301  PMID: 2469760

Abstract

Human T lymphocyte clones specific for pertussis toxin (PT) were used to analyze the fine specificity of the response to PT, the basic component of new acellular vaccines against whooping cough. The majority (83%) of the clones specific for PT recognized S1, the subunit that in animal models has been shown to be highly immunogenic. To map T cell epitopes on S1, 18 S1-specific clones were tested for recognition of recombinant fragments representing NH2-terminal and COOH-terminal deletions of S1 and two recombinant S1 subunits containing amino acid substitutions. This approach led to the identification of three regions of the protein as the sequences containing T cell antigenic sites: 1- 42, 181-211, and 212-235. Synthetic peptides were eventually used for a finer localization of the T cell epitopes. Two peptides, one of 13 residues (27-39) at the NH2 terminus and one of 24 residues (171-194) at the COOH terminus, stimulated proliferation of three and four clones, respectively. Both peptides are recognized in association with HLA DR1 molecules. These results stress the role of S1 in the immune response to PT and provide data useful for the development of a recombinant or synthetic antipertussis vaccine containing T cell epitopes from S1.

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Selected References

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  1. Aricò B., Rappuoli R. Bordetella parapertussis and Bordetella bronchiseptica contain transcriptionally silent pertussis toxin genes. J Bacteriol. 1987 Jun;169(6):2847–2853. doi: 10.1128/jb.169.6.2847-2853.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Barbieri J. T., Cortina G. ADP-ribosyltransferase mutations in the catalytic S-1 subunit of pertussis toxin. Infect Immun. 1988 Aug;56(8):1934–1941. doi: 10.1128/iai.56.8.1934-1941.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Berzofsky J. A., Cease K. B., Cornette J. L., Spouge J. L., Margalit H., Berkower I. J., Good M. F., Miller L. H., DeLisi C. Protein antigenic structures recognized by T cells: potential applications to vaccine design. Immunol Rev. 1987 Aug;98:9–52. doi: 10.1111/j.1600-065x.1987.tb00518.x. [DOI] [PubMed] [Google Scholar]
  4. 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]
  5. Cherry J. D. The epidemiology of pertussis and pertussis immunization in the United Kingdom and the United States: a comparative study. Curr Probl Pediatr. 1984 Feb;14(2):1–78. doi: 10.1016/0045-9380(84)90016-1. [DOI] [PubMed] [Google Scholar]
  6. 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]
  7. De Magistris M. T., Romano M., Nuti S., Rappuoli R., Tagliabue A. Dissecting human T cell responses against Bordetella species. J Exp Med. 1988 Oct 1;168(4):1351–1362. doi: 10.1084/jem.168.4.1351. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Finkelstein R. A., Burks M. F., Zupan A., Dallas W. S., Jacob C. O., Ludwig D. S. Epitopes of the cholera family of enterotoxins. Rev Infect Dis. 1987 May-Jun;9(3):544–561. doi: 10.1093/clinids/9.3.544. [DOI] [PubMed] [Google Scholar]
  9. Katada T., Ui M. Direct modification of the membrane adenylate cyclase system by islet-activating protein due to ADP-ribosylation of a membrane protein. Proc Natl Acad Sci U S A. 1982 May;79(10):3129–3133. doi: 10.1073/pnas.79.10.3129. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. 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]
  11. Manning D. R., Fraser B. A., Kahn R. A., Gilman A. G. ADP-ribosylation of transducin by islet-activation protein. Identification of asparagine as the site of ADP-ribosylation. J Biol Chem. 1984 Jan 25;259(2):749–756. [PubMed] [Google Scholar]
  12. 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]
  13. Munoz J. J., Arai H., Bergman R. K., Sadowski P. L. Biological activities of crystalline pertussigen from Bordetella pertussis. Infect Immun. 1981 Sep;33(3):820–826. doi: 10.1128/iai.33.3.820-826.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. 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]
  15. 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]
  16. Oksenberg J. R., Judd A. K., Ko C., Lim M., Fernandez R., Schoolnik G. K., Steinman L. MHC-restricted recognition of immunogenic T cell epitopes of pertussis toxin reveals determinants in man distinct from the ADP-ribosylase active site. J Exp Med. 1988 Nov 1;168(5):1855–1864. doi: 10.1084/jem.168.5.1855. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Pappenheimer A. M., Jr, Uchida T., Harper A. A. An immunological study of the diphtheria toxin molecule. Immunochemistry. 1972 Sep;9(9):891–906. doi: 10.1016/0019-2791(72)90163-2. [DOI] [PubMed] [Google Scholar]
  18. Pizza M., Bartoloni A., Prugnola A., Silvestri S., Rappuoli R. Subunit S1 of pertussis toxin: mapping of the regions essential for ADP-ribosyltransferase activity. Proc Natl Acad Sci U S A. 1988 Oct;85(20):7521–7525. doi: 10.1073/pnas.85.20.7521. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Romanus V., Jonsell R., Bergquist S. O. Pertussis in Sweden after the cessation of general immunization in 1979. Pediatr Infect Dis J. 1987 Apr;6(4):364–371. doi: 10.1097/00006454-198704000-00005. [DOI] [PubMed] [Google Scholar]
  20. Rosén A., Persson K., Klein G. Human monoclonal antibodies to a genus-specific chlamydial antigen, produced by EBV-transformed B cells. J Immunol. 1983 Jun;130(6):2899–2902. [PubMed] [Google Scholar]
  21. Rutter D. A., Ashworth L. A., Day A., Funnell S., Lovell F., Robinson A. Trial of a new acellular pertussis vaccine in healthy adult volunteers. Vaccine. 1988 Feb;6(1):29–32. doi: 10.1016/0264-410x(88)90010-2. [DOI] [PubMed] [Google Scholar]
  22. Sato H., Ito A., Chiba J., Sato Y. Monoclonal antibody against pertussis toxin: effect on toxin activity and pertussis infections. Infect Immun. 1984 Nov;46(2):422–428. doi: 10.1128/iai.46.2.422-428.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. 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]
  24. Sekura R. D., Fish F., Manclark C. R., Meade B., Zhang Y. L. Pertussis toxin. Affinity purification of a new ADP-ribosyltransferase. J Biol Chem. 1983 Dec 10;258(23):14647–14651. [PubMed] [Google Scholar]
  25. Sinigaglia F., Scheidegger D., Garotta G., Scheper R., Pletscher M., Lanzavecchia A. Isolation and characterization of Ni-specific T cell clones from patients with Ni-contact dermatitis. J Immunol. 1985 Dec;135(6):3929–3932. [PubMed] [Google Scholar]
  26. Tamura M., Nogimori K., Murai S., Yajima M., Ito K., Katada T., Ui M., Ishii S. Subunit structure of islet-activating protein, pertussis toxin, in conformity with the A-B model. Biochemistry. 1982 Oct 26;21(22):5516–5522. doi: 10.1021/bi00265a021. [DOI] [PubMed] [Google Scholar]
  27. Vogel F. R., Klein T. W., Stewart W. E., 2nd, Igarashi T., Friedman H. Immune suppression and induction of gamma interferon by pertussis toxin. Infect Immun. 1985 Jul;49(1):90–97. doi: 10.1128/iai.49.1.90-97.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]

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