Skip to main content
PMC home page
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
. 1989 Mar;86(5):1629–1633. doi: 10.1073/pnas.86.5.1629

Vaccine T-cell epitope selection by a peptide competition assay.

J Kilgus 1, P Romagnoli 1, M Guttinger 1, D Stuber 1, L Adorini 1, F Sinigaglia 1
PMCID: PMC286752  PMID: 2466297

Abstract

The binding of several peptides derived from the Plasmodium falciparum circumsporozoite protein (CS protein) to the human major histocompatibility complex class II proteins HLA-DR5 and -DRw6 was examined in a competition assay. Fixed antigen-presenting cells (APCs) were incubated with various concentrations of each peptide and suboptimal concentrations of stimulator peptides. The binding of the CS peptides to DR5 or DRw6 proteins was then determined in a proliferation assay using two established DR5 or DRw6-restricted T-cell clones with specificity for the stimulator peptides as responder cells. One of five CS peptides, comprising together about 50% of the CS protein sequence, was found to compete with the binding of the stimulator peptides to DR5 and DRw6. The CS peptide CS-(378-398), binding to DR5 and DRw6, was then shown to be able to induce primary in vitro responses of T cells from donors with DR5 and DRw6 haplotypes. CS-(378-398)-induced T-cell clones responded not only to the homologous peptide but also to the native CS protein in the presence of appropriate APCs. The strategy we have applied is of considerable general interest for the engineering of vaccines against any pathogen, since it greatly facilitates the selection of appropriate T-cell epitopes to be incorporated in the vaccine.

Full text

PDF
1629

Selected References

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

  1. Amit A. G., Mariuzza R. A., Phillips S. E., Poljak R. J. Three-dimensional structure of an antigen-antibody complex at 2.8 A resolution. Science. 1986 Aug 15;233(4765):747–753. doi: 10.1126/science.2426778. [DOI] [PubMed] [Google Scholar]
  2. Buus S., Sette A., Colon S. M., Miles C., Grey H. M. The relation between major histocompatibility complex (MHC) restriction and the capacity of Ia to bind immunogenic peptides. Science. 1987 Mar 13;235(4794):1353–1358. doi: 10.1126/science.2435001. [DOI] [PubMed] [Google Scholar]
  3. Carbone F. R., Moore M. W., Sheil J. M., Bevan M. J. Induction of cytotoxic T lymphocytes by primary in vitro stimulation with peptides. J Exp Med. 1988 Jun 1;167(6):1767–1779. doi: 10.1084/jem.167.6.1767. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Certa U., Bannwarth W., Stüber D., Gentz R., Lanzer M., Le Grice S., Guillot F., Wendler I., Hunsmann G., Bujard H. Subregions of a conserved part of the HIV gp41 transmembrane protein are differentially recognized by antibodies of infected individuals. EMBO J. 1986 Nov;5(11):3051–3056. doi: 10.1002/j.1460-2075.1986.tb04605.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Crisanti A., Müller H. M., Hilbich C., Sinigaglia F., Matile H., McKay M., Scaife J., Beyreuther K., Bujard H. Epitopes recognized by human T cells map within the conserved part of the GP190 of P. falciparum. Science. 1988 Jun 3;240(4857):1324–1326. doi: 10.1126/science.2453924. [DOI] [PubMed] [Google Scholar]
  6. 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]
  7. Good M. F., Pombo D., Quakyi I. A., Riley E. M., Houghten R. A., Menon A., Alling D. W., Berzofsky J. A., Miller L. H. Human T-cell recognition of the circumsporozoite protein of Plasmodium falciparum: immunodominant T-cell domains map to the polymorphic regions of the molecule. Proc Natl Acad Sci U S A. 1988 Feb;85(4):1199–1203. doi: 10.1073/pnas.85.4.1199. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Guillet J. G., Lai M. Z., Briner T. J., Buus S., Sette A., Grey H. M., Smith J. A., Gefter M. L. Immunological self, nonself discrimination. Science. 1987 Feb 20;235(4791):865–870. doi: 10.1126/science.2433769. [DOI] [PubMed] [Google Scholar]
  9. Guillet J. G., Lai M. Z., Briner T. J., Smith J. A., Gefter M. L. Interaction of peptide antigens and class II major histocompatibility complex antigens. Nature. 1986 Nov 20;324(6094):260–262. doi: 10.1038/324260a0. [DOI] [PubMed] [Google Scholar]
  10. Guttinger M., Caspers P., Takacs B., Trzeciak A., Gillessen D., Pink J. R., Sinigaglia F. Human T cells recognize polymorphic and non-polymorphic regions of the Plasmodium falciparum circumsporozoite protein. EMBO J. 1988 Aug;7(8):2555–2558. doi: 10.1002/j.1460-2075.1988.tb03104.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Kaufman J. F., Strominger J. L. HLA-DR light chain has a polymorphic N-terminal region and a conserved immunoglobulin-like C-terminal region. Nature. 1982 Jun 24;297(5868):694–697. doi: 10.1038/297694a0. [DOI] [PubMed] [Google Scholar]
  12. Ogasawara K., Maloy W. L., Schwartz R. H. Failure to find holes in the T-cell repertoire. 1987 Jan 29-Feb 4Nature. 325(6103):450–452. doi: 10.1038/325450a0. [DOI] [PubMed] [Google Scholar]
  13. Schofield L., Villaquiran J., Ferreira A., Schellekens H., Nussenzweig R., Nussenzweig V. Gamma interferon, CD8+ T cells and antibodies required for immunity to malaria sporozoites. Nature. 1987 Dec 17;330(6149):664–666. doi: 10.1038/330664a0. [DOI] [PubMed] [Google Scholar]
  14. 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]
  15. Sinigaglia F., Guttinger M., Gillessen D., Doran D. M., Takacs B., Matile H., Trzeciak A., Pink J. R. Epitopes recognized by human T lymphocytes on malaria circumsporozoite protein. Eur J Immunol. 1988 Apr;18(4):633–636. doi: 10.1002/eji.1830180422. [DOI] [PubMed] [Google Scholar]
  16. Sinigaglia F., Guttinger M., Kilgus J., Doran D. M., Matile H., Etlinger H., Trzeciak A., Gillessen D., Pink J. R. A malaria T-cell epitope recognized in association with most mouse and human MHC class II molecules. Nature. 1988 Dec 22;336(6201):778–780. doi: 10.1038/336778a0. [DOI] [PubMed] [Google Scholar]
  17. Sinigaglia F., Matile H., Pink J. R. Plasmodium falciparum-specific human T cell clones: evidence for helper and cytotoxic activities. Eur J Immunol. 1987 Feb;17(2):187–192. doi: 10.1002/eji.1830170206. [DOI] [PubMed] [Google Scholar]
  18. Sinigaglia F., Takacs B., Jacot H., Matile H., Pink J. R., Crisanti A., Bujard H. Nonpolymorphic regions of p190, a protein of the Plasmodium falciparum erythrocytic stage, contain both T and B cell epitopes. J Immunol. 1988 May 15;140(10):3568–3572. [PubMed] [Google Scholar]
  19. Spitalny G. L., Verhave J. P., Meuwissen J. H., Nussenzweig R. S. Plasmodium berghei: T cell dependence of sporozoite-induced immunity in rodents. Exp Parasitol. 1977 Jun;42(1):73–81. doi: 10.1016/0014-4894(77)90063-7. [DOI] [PubMed] [Google Scholar]
  20. Trucco M. M., Garotta G., Stocker J. W., Ceppellini R. Murine monoclonal antibodies against HLA structures. Immunol Rev. 1979;47:219–252. doi: 10.1111/j.1600-065x.1979.tb00295.x. [DOI] [PubMed] [Google Scholar]
  21. Watson A. J., DeMars R., Trowbridge I. S., Bach F. H. Detection of a novel human class II HLA antigen. 1983 Jul 28-Aug 3Nature. 304(5924):358–361. doi: 10.1038/304358a0. [DOI] [PubMed] [Google Scholar]
  22. Weiss W. R., Sedegah M., Beaudoin R. L., Miller L. H., Good M. F. CD8+ T cells (cytotoxic/suppressors) are required for protection in mice immunized with malaria sporozoites. Proc Natl Acad Sci U S A. 1988 Jan;85(2):573–576. doi: 10.1073/pnas.85.2.573. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Zavala F., Tam J. P., Barr P. J., Romero P. J., Ley V., Nussenzweig R. S., Nussenzweig V. Synthetic peptide vaccine confers protection against murine malaria. J Exp Med. 1987 Nov 1;166(5):1591–1596. doi: 10.1084/jem.166.5.1591. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Ziegler A., Milstein C. A small polypeptide different from beta2-microglobin associated with a human cell surface antigen. Nature. 1979 May 17;279(5710):243–244. doi: 10.1038/279243a0. [DOI] [PubMed] [Google Scholar]
  25. del Portillo H. A., Nussenzweig R. S., Enea V. Circumsporozoite gene of a Plasmodium falciparum strain from Thailand. Mol Biochem Parasitol. 1987 Jul;24(3):289–294. doi: 10.1016/0166-6851(87)90161-7. [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