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 May;86(10):3768–3772. doi: 10.1073/pnas.86.10.3768

A protective monoclonal antibody recognizes a linear epitope in the precursor to the major merozoite antigens of Plasmodium chabaudi adami.

A M Lew 1, C J Langford 1, R F Anders 1, D J Kemp 1, A Saul 1, C Fardoulys 1, M Geysen 1, M Sheppard 1
PMCID: PMC287221  PMID: 2471191

Abstract

The monoclonal antibody 5C10/66 was shown to afford strong protection in mice against fulminating Plasmodium chabaudi adami infection. This was remarkable, as immunity to this organism is regarded to be mainly T-cell mediated. This antibody identified a 250-kDa molecule in schizonts and an 83-kDa fragment in merozoites. A cDNA clone selected by 5C10/66 was the homologue of the Plasmodium falciparum precursor to the major merozoite surface antigen (PMMSA). Comparison with the P. falciparum sequence showed that the P. chabaudi adami clone encoded the middle portion of the gene and that it can also be divided into variable and conserved blocks. Screening of a set of all possible octamer peptides predicted by the cDNA clone revealed that the core epitope of 5C10/66 was Glu-Thr-Thr-Glu-Thr. This region resides in a variable block of PMMSA.

Full text

PDF
3771

Images in this article

3769Image
on p.3769
3769Image
on p.3769

Selected References

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

  1. Boyle D. B., Newbold C. I., Smith C. C., Brown K. N. Monoclonal antibodies that protect in vivo against Plasmodium chabaudi recognize a 250,000-dalton parasite polypeptide. Infect Immun. 1982 Oct;38(1):94–102. doi: 10.1128/iai.38.1.94-102.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Brake D. A., Long C. A., Weidanz W. P. Adoptive protection against Plasmodium chabaudi adami malaria in athymic nude mice by a cloned T cell line. J Immunol. 1988 Mar 15;140(6):1989–1993. [PubMed] [Google Scholar]
  3. Brown K. N., Jarra W., Newbold C. I., Schryer M. Variability in parasite protein antigen structure and protective immunity to malaria. Ann Inst Pasteur Immunol. 1985 Jan-Feb;136C(1):11–23. [PubMed] [Google Scholar]
  4. Burns J. M., Jr, Daly T. M., Vaidya A. B., Long C. A. The 3' portion of the gene for a Plasmodium yoelii merozoite surface antigen encodes the epitope recognized by a protective monoclonal antibody. Proc Natl Acad Sci U S A. 1988 Jan;85(2):602–606. doi: 10.1073/pnas.85.2.602. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Cavacini L. A., Long C. A., Weidanz W. P. T-cell immunity in murine malaria: adoptive transfer of resistance to Plasmodium chabaudi adami in nude mice with splenic T cells. Infect Immun. 1986 Jun;52(3):637–643. doi: 10.1128/iai.52.3.637-643.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Crewther P. E., Bianco A. E., Brown G. V., Coppel R. L., Stahl H. D., Kemp D. J., Anders R. F. Affinity purification of human antibodies directed against cloned antigens of Plasmodium falciparum. J Immunol Methods. 1986 Feb 12;86(2):257–264. doi: 10.1016/0022-1759(86)90462-x. [DOI] [PubMed] [Google Scholar]
  7. David P. H., Hommel M., Benichou J. C., Eisen H. A., da Silva L. H. Isolation of malaria merozoites: release of Plasmodium chabaudi merozoites from schizonts bound to immobilized concanavalin A. Proc Natl Acad Sci U S A. 1978 Oct;75(10):5081–5084. doi: 10.1073/pnas.75.10.5081. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Epstein N., Miller L. H., Kaushel D. C., Udeinya I. J., Rener J., Howard R. J., Asofsky R., Aikawa M., Hess R. L. Monoclonal antibodies against a specific surface determinant on malarial (Plasmodium knowlesi) merozoites block erythrocyte invasion. J Immunol. 1981 Jul;127(1):212–217. [PubMed] [Google Scholar]
  9. Geysen H. M., Rodda S. J., Mason T. J., Tribbick G., Schoofs P. G. Strategies for epitope analysis using peptide synthesis. J Immunol Methods. 1987 Sep 24;102(2):259–274. doi: 10.1016/0022-1759(87)90085-8. [DOI] [PubMed] [Google Scholar]
  10. Grun J. L., Weidanz W. P. Immunity to Plasmodium chabaudi adami in the B-cell-deficient mouse. Nature. 1981 Mar 12;290(5802):143–145. doi: 10.1038/290143a0. [DOI] [PubMed] [Google Scholar]
  11. Holder A. A., Freeman R. R. Immunization against blood-stage rodent malaria using purified parasite antigens. Nature. 1981 Nov 26;294(5839):361–364. doi: 10.1038/294361a0. [DOI] [PubMed] [Google Scholar]
  12. Holder A. A., Lockyer M. J., Odink K. G., Sandhu J. S., Riveros-Moreno V., Nicholls S. C., Hillman Y., Davey L. S., Tizard M. L., Schwarz R. T. Primary structure of the precursor to the three major surface antigens of Plasmodium falciparum merozoites. Nature. 1985 Sep 19;317(6034):270–273. doi: 10.1038/317270a0. [DOI] [PubMed] [Google Scholar]
  13. Holder A. A. The precursor to major merozoite surface antigens: structure and role in immunity. Prog Allergy. 1988;41:72–97. [PubMed] [Google Scholar]
  14. Jarra W., Hills L. A., March J. C., Brown K. N. Protective immunity to malaria. Studies with cloned lines of Plasmodium chabaudi chabaudi and P. berghei in CBA/Ca mice. II. The effectiveness and inter- or intra-species specificity of the passive transfer of immunity with serum. Parasite Immunol. 1986 May;8(3):239–254. doi: 10.1111/j.1365-3024.1986.tb01036.x. [DOI] [PubMed] [Google Scholar]
  15. Lew A. M., Margulies D. H., Maloy W. L., Lillehoj E. P., McCluskey J., Coligan J. E. Alternative protein products with different carboxyl termini from a single class I gene, H-2Kb. Proc Natl Acad Sci U S A. 1986 Aug;83(16):6084–6088. doi: 10.1073/pnas.83.16.6084. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Lyon J. A., Geller R. H., Haynes J. D., Chulay J. D., Weber J. L. Epitope map and processing scheme for the 195,000-dalton surface glycoprotein of Plasmodium falciparum merozoites deduced from cloned overlapping segments of the gene. Proc Natl Acad Sci U S A. 1986 May;83(9):2989–2993. doi: 10.1073/pnas.83.9.2989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Majarian W. R., Daly T. M., Weidanz W. P., Long C. A. Passive immunization against murine malaria with an IgG3 monoclonal antibody. J Immunol. 1984 Jun;132(6):3131–3137. [PubMed] [Google Scholar]
  18. Patarroyo M. E., Amador R., Clavijo P., Moreno A., Guzman F., Romero P., Tascon R., Franco A., Murillo L. A., Ponton G. A synthetic vaccine protects humans against challenge with asexual blood stages of Plasmodium falciparum malaria. Nature. 1988 Mar 10;332(6160):158–161. doi: 10.1038/332158a0. [DOI] [PubMed] [Google Scholar]
  19. Perrin L. H., Loche M., Dedet J. P., Roussilhon C., Fandeur T. Immunization against Plasmodium falciparum asexual blood stages using soluble antigens. Clin Exp Immunol. 1984 Apr;56(1):67–72. [PMC free article] [PubMed] [Google Scholar]
  20. Peterson M. G., Coppel R. L., McIntyre P., Langford C. J., Woodrow G., Brown G. V., Anders R. F., Kemp D. J. Variation in the precursor to the major merozoite surface antigens of Plasmodium falciparum. Mol Biochem Parasitol. 1988 Jan 15;27(2-3):291–301. doi: 10.1016/0166-6851(88)90049-7. [DOI] [PubMed] [Google Scholar]
  21. Peterson M. G., Coppel R. L., Moloney M. B., Kemp D. J. Third form of the precursor to the major merozoite surface antigens of Plasmodium falciparum. Mol Cell Biol. 1988 Jun;8(6):2664–2667. doi: 10.1128/mcb.8.6.2664. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Sanger F., Coulson A. R., Barrell B. G., Smith A. J., Roe B. A. Cloning in single-stranded bacteriophage as an aid to rapid DNA sequencing. J Mol Biol. 1980 Oct 25;143(2):161–178. doi: 10.1016/0022-2836(80)90196-5. [DOI] [PubMed] [Google Scholar]
  23. Schmidt-Ullrich R., Lightholder J., Monroe M. T. Protective Plasmodium knowlesi Mr 74,000 antigen in membranes of schizont-infected rhesus erythrocytes. J Exp Med. 1983 Jul 1;158(1):146–158. doi: 10.1084/jem.158.1.146. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Siddiqui W. A., Tam L. Q., Kramer K. J., Hui G. S., Case S. E., Yamaga K. M., Chang S. P., Chan E. B., Kan S. C. Merozoite surface coat precursor protein completely protects Aotus monkeys against Plasmodium falciparum malaria. Proc Natl Acad Sci U S A. 1987 May;84(9):3014–3018. doi: 10.1073/pnas.84.9.3014. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Tanabe K., Mackay M., Goman M., Scaife J. G. Allelic dimorphism in a surface antigen gene of the malaria parasite Plasmodium falciparum. J Mol Biol. 1987 May 20;195(2):273–287. doi: 10.1016/0022-2836(87)90649-8. [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