Skip to main content
Infection and Immunity logoLink to Infection and Immunity
. 1992 Feb;60(2):443–449. doi: 10.1128/iai.60.2.443-449.1992

Involvement of Pf155/RESA and cross-reactive antigens in Plasmodium falciparum merozoite invasion in vitro.

B Wåhlin 1, A Sjölander 1, N Ahlborg 1, R Udomsangpetch 1, A Scherf 1, D Mattei 1, K Berzins 1, P Perlmann 1
PMCID: PMC257647  PMID: 1730474

Abstract

Lines of Plasmodium falciparum FCR3 either expressing or not expressing the blood-stage antigen Pf155/RESA were used to analyze the possible involvement of this antigen in the merozoite invasion process in vitro. Antibodies from human sera, affinity purified on synthetic peptides corresponding to C-terminal repeated sequences in Pf155/RESA, were shown to inhibit merozoite invasion of both types of parasites with similar efficiency. Reversal of the invasion inhibition by fusion proteins containing repeated sequences of Pf155/RESA but not of the cross-reactive antigens Ag332 and Pf11.1 indicated that the inhibitory antibodies had similar target antigens in both Pf155/RESA+ and Pf155/RESA- parasites that involved cross-reacting epitopes present in Pf155/RESA. Rabbit antibodies specific for Pf155/RESA repeats inhibited merozoite invasion of Pf155/RESA expressing parasites efficiently but had no or very small effect on the invasion of Pf155/RESA-deficient parasites. In contrast, rabbit antibodies specific for Ag332 repeats as well as human antibodies affinity purified on synthetic Ag332 peptides inhibited merozoite invasion of both types of parasites with high efficiency. A similar inhibition pattern was seen with the human monoclonal antibody 33G2, which has specificity for Ag332 but also cross-reacts with Pf155/RESA and Pf11.1. Taken together, our data suggest that Pf155/RESA and related cross-reactive antigens as well as Ag332 are involved in the merozoite invasion process and may constitute targets for invasion inhibitory antibodies.

Full text

PDF
443

Selected References

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

  1. Ahlborg N., Berzins K., Perlmann P. Definition of the epitope recognized by the Plasmodium falciparum-reactive human monoclonal antibody 33G2. Mol Biochem Parasitol. 1991 May;46(1):89–95. doi: 10.1016/0166-6851(91)90202-h. [DOI] [PubMed] [Google Scholar]
  2. Aikawa M., Torii M., Sjölander A., Berzins K., Perlmann P., Miller L. H. Pf155/RESA antigen is localized in dense granules of Plasmodium falciparum merozoites. Exp Parasitol. 1990 Oct;71(3):326–329. doi: 10.1016/0014-4894(90)90037-d. [DOI] [PubMed] [Google Scholar]
  3. Anders R. F., Coppel R. L., Brown G. V., Kemp D. J. Antigens with repeated amino acid sequences from the asexual blood stages of Plasmodium falciparum. Prog Allergy. 1988;41:148–172. [PubMed] [Google Scholar]
  4. Anders R. F. Multiple cross-reactivities amongst antigens of Plasmodium falciparum impair the development of protective immunity against malaria. Parasite Immunol. 1986 Nov;8(6):529–539. doi: 10.1111/j.1365-3024.1986.tb00867.x. [DOI] [PubMed] [Google Scholar]
  5. Ardeshir F., Howard R. F., Viriyakosol S., Arad O., Reese R. T. Cross-reactive asparagine-rich determinants shared between several blood-stage antigens of Plasmodium falciparum and the circumsporozoite protein. Mol Biochem Parasitol. 1990 Apr;40(1):113–128. doi: 10.1016/0166-6851(90)90085-z. [DOI] [PubMed] [Google Scholar]
  6. Berzins K., Perlmann H., Wåhlin B., Carlsson J., Wahlgren M., Udomsangpetch R., Björkman A., Patarroyo M. E., Perlmann P. Rabbit and human antibodies to a repeated amino acid sequence of a Plasmodium falciparum antigen, Pf 155, react with the native protein and inhibit merozoite invasion. Proc Natl Acad Sci U S A. 1986 Feb;83(4):1065–1069. doi: 10.1073/pnas.83.4.1065. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Cappai R., van Schravendijk M. R., Anders R. F., Peterson M. G., Thomas L. M., Cowman A. F., Kemp D. J. Expression of the RESA gene in Plasmodium falciparum isolate FCR3 is prevented by a subtelomeric deletion. Mol Cell Biol. 1989 Aug;9(8):3584–3587. doi: 10.1128/mcb.9.8.3584. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Carlsson J., Berzins K., Perlmann H., Perlmann P. Studies on Pf155/RESA and other soluble antigens from in vitro cultured Plasmodium falciparum. Parasitol Res. 1991;77(1):27–32. doi: 10.1007/BF00934380. [DOI] [PubMed] [Google Scholar]
  9. Carlsson J., Udomsangpetch R., Wåhlin B., Ahlborg N., Berzins K., Perlmann P. Plasmodium falciparum: differential parasite reactivity of rabbit antibodies to repeated sequences in the antigen Pf155/RESA. Exp Parasitol. 1990 Oct;71(3):314–325. doi: 10.1016/0014-4894(90)90036-c. [DOI] [PubMed] [Google Scholar]
  10. Coppel R. L., Cowman A. F., Anders R. F., Bianco A. E., Saint R. B., Lingelbach K. R., Kemp D. J., Brown G. V. Immune sera recognize on erythrocytes Plasmodium falciparum antigen composed of repeated amino acid sequences. 1984 Aug 30-Sep 5Nature. 310(5980):789–792. doi: 10.1038/310789a0. [DOI] [PubMed] [Google Scholar]
  11. Coppel R. L., Lustigman S., Murray L., Anders R. F. MESA is a Plasmodium falciparum phosphoprotein associated with the erythrocyte membrane skeleton. Mol Biochem Parasitol. 1988 Dec;31(3):223–231. doi: 10.1016/0166-6851(88)90152-1. [DOI] [PubMed] [Google Scholar]
  12. Culvenor J. G., Day K. P., Anders R. F. Plasmodium falciparum ring-infected erythrocyte surface antigen is released from merozoite dense granules after erythrocyte invasion. Infect Immun. 1991 Mar;59(3):1183–1187. doi: 10.1128/iai.59.3.1183-1187.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Foley M., Tilley L., Sawyer W. H., Anders R. F. The ring-infected erythrocyte surface antigen of Plasmodium falciparum associates with spectrin in the erythrocyte membrane. Mol Biochem Parasitol. 1991 May;46(1):137–147. doi: 10.1016/0166-6851(91)90207-m. [DOI] [PubMed] [Google Scholar]
  14. Hadley T. J. Invasion of erythrocytes by malaria parasites: a cellular and molecular overview. Annu Rev Microbiol. 1986;40:451–477. doi: 10.1146/annurev.mi.40.100186.002315. [DOI] [PubMed] [Google Scholar]
  15. Harboe N., Ingild A. Immunization, isolation of immunoglobulins, estimation of antibody titre. Scand J Immunol Suppl. 1973;1:161–164. doi: 10.1111/j.1365-3083.1973.tb03798.x. [DOI] [PubMed] [Google Scholar]
  16. Houghten R. A. General method for the rapid solid-phase synthesis of large numbers of peptides: specificity of antigen-antibody interaction at the level of individual amino acids. Proc Natl Acad Sci U S A. 1985 Aug;82(15):5131–5135. doi: 10.1073/pnas.82.15.5131. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Kilejian A., Rashid M. A., Aikawa M., Aji T., Yang Y. F. Selective association of a fragment of the knob protein with spectrin, actin and the red cell membrane. Mol Biochem Parasitol. 1991 Feb;44(2):175–181. doi: 10.1016/0166-6851(91)90003-o. [DOI] [PubMed] [Google Scholar]
  18. Merrifield R. B. Solid-phase peptide synthesis. Adv Enzymol Relat Areas Mol Biol. 1969;32:221–296. doi: 10.1002/9780470122778.ch6. [DOI] [PubMed] [Google Scholar]
  19. Perlmann H. K., Berzins K., Wåhlin B., Udomsangpetch R., Ruangjirachuporn W., Wahlgren M., Perlmann P. H. Absence of antigenic diversity in Pf155, a major parasite antigen in membranes of erythrocytes infected with Plasmodium falciparum. J Clin Microbiol. 1987 Dec;25(12):2347–2354. doi: 10.1128/jcm.25.12.2347-2354.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Perlmann H., Berzins K., Wahlgren M., Carlsson J., Björkman A., Patarroyo M. E., Perlmann P. Antibodies in malarial sera to parasite antigens in the membrane of erythrocytes infected with early asexual stages of Plasmodium falciparum. J Exp Med. 1984 Jun 1;159(6):1686–1704. doi: 10.1084/jem.159.6.1686. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Pologe L. G., de Bruin D., Ravetch J. V. A and T homopolymeric stretches mediate a DNA inversion in Plasmodium falciparum which results in loss of gene expression. Mol Cell Biol. 1990 Jun;10(6):3243–3246. doi: 10.1128/mcb.10.6.3243. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Ruangjirachuporn W., Udomsangpetch R., Carlsson J., Drenckhahn D., Perlmann P., Berzins K. Plasmodium falciparum: analysis of the interaction of antigen Pf155/RESA with the erythrocyte membrane. Exp Parasitol. 1991 Jul;73(1):62–72. doi: 10.1016/0014-4894(91)90008-k. [DOI] [PubMed] [Google Scholar]
  23. Ruangjirachuporn W., Wåhlin B., Perlmann H., Carlsson J., Berzins K., Wahlgren M., Udomsangpetch R., Wigzell H., Perlmann P. Monoclonal antibodies to a synthetic peptide corresponding to a repeated sequence in the Plasmodium falciparum antigen Pf155. Mol Biochem Parasitol. 1988 May;29(1):19–28. doi: 10.1016/0166-6851(88)90115-6. [DOI] [PubMed] [Google Scholar]
  24. Sam-Yellowe T. Y., Shio H., Perkins M. E. Secretion of Plasmodium falciparum rhoptry protein into the plasma membrane of host erythrocytes. J Cell Biol. 1988 May;106(5):1507–1513. doi: 10.1083/jcb.106.5.1507. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Scherf A., Hilbich C., Sieg K., Mattei D., Mercereau-Puijalon O., Müller-Hill B. The 11-1 gene of Plasmodium falciparum codes for distinct fast evolving repeats. EMBO J. 1988 Apr;7(4):1129–1137. doi: 10.1002/j.1460-2075.1988.tb02922.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Sjölander A., Ståhl S., Nygren P. A., Aslund L., Ahlborg N., Wåhlin B., Scherf A., Berzins K., Uhlén M., Perlmann P. Immunogenicity and antigenicity in rabbits of a repeated sequence of Plasmodium falciparum antigen Pf155/RESA fused to two immunoglobulin G-binding domains of staphylococcal protein A. Infect Immun. 1990 Apr;58(4):854–859. doi: 10.1128/iai.58.4.854-859.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Ståhl S., Sjölander A., Hansson M., Nygren P. A., Uhlén M. A general strategy for polymerization, assembly and expression of epitope-carrying peptides applied to the Plasmodium falciparum antigen Pf155/RESA. Gene. 1990 May 14;89(2):187–193. doi: 10.1016/0378-1119(90)90005-c. [DOI] [PubMed] [Google Scholar]
  28. Ståhl S., Sjölander A., Nygren P. A., Berzins K., Perlmann P., Uhlén M. A dual expression system for the generation, analysis and purification of antibodies to a repeated sequence of the Plasmodium falciparum antigen Pf155/RESA. J Immunol Methods. 1989 Nov 13;124(1):43–52. doi: 10.1016/0022-1759(89)90184-1. [DOI] [PubMed] [Google Scholar]
  29. Torii M., Adams J. H., Miller L. H., Aikawa M. Release of merozoite dense granules during erythrocyte invasion by Plasmodium knowlesi. Infect Immun. 1989 Oct;57(10):3230–3233. doi: 10.1128/iai.57.10.3230-3233.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Trager W., Jensen J. B. Human malaria parasites in continuous culture. Science. 1976 Aug 20;193(4254):673–675. doi: 10.1126/science.781840. [DOI] [PubMed] [Google Scholar]
  31. Udomsangpetch R., Carlsson J., Wåhlin B., Holmquist G., Ozaki L. S., Scherf A., Mattei D., Mercereau-Puijalon O., Uni S., Aikawa M. Reactivity of the human monoclonal antibody 33G2 with repeated sequences of three distinct Plasmodium falciparum antigens. J Immunol. 1989 May 15;142(10):3620–3626. [PubMed] [Google Scholar]
  32. Udomsangpetch R., Lundgren K., Berzins K., Wåhlin B., Perlmann H., Troye-Blomberg M., Carlsson J., Wahlgren M., Perlmann P., Björkman A. Human monoclonal antibodies to Pf 155, a major antigen of malaria parasite Plasmodium falciparum. Science. 1986 Jan 3;231(4733):57–59. doi: 10.1126/science.3510452. [DOI] [PubMed] [Google Scholar]
  33. Wåhlin B., Wahlgren M., Perlmann H., Berzins K., Björkman A., Patarroyo M. E., Perlmann P. Human antibodies to a Mr 155,000 Plasmodium falciparum antigen efficiently inhibit merozoite invasion. Proc Natl Acad Sci U S A. 1984 Dec;81(24):7912–7916. doi: 10.1073/pnas.81.24.7912. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Infection and Immunity are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES