Abstract
Merozoite surface antigen MSA-2 of the human parasite Plasmodium falciparum is being considered for the development of a malaria vaccine. The antigen is polymorphic, and specific monoclonal antibodies differentiate five serological variants of MSA-2 among 25 parasite isolates. The variants are grouped into two major serogroups, A and B. Genes encoding two different variants from serogroup A have been sequenced, and their DNA together with deduced amino acid sequences were compared with sequences encoded by other alleles. The comparison shows that the serological classification reflects differences in DNA sequences and deduced primary structure of MSA-2 variants and serogroups. Thus, the overall homologies of DNA and amino acid sequences are over 95% among variants in the same serogroup. In contrast, similarities between the group A variants and a group B variant are only 70 and 64% for DNA and amino acid sequences, respectively. We propose that the MSA-2 protein is encoded by two highly divergent groups of alleles, with limited additional polymorphism displayed within each group.
Full text
PDF








Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Arnot D. Malaria and the major histocompatibility complex. Parasitol Today. 1989 May;5(5):138–142. doi: 10.1016/0169-4758(89)90077-x. [DOI] [PubMed] [Google Scholar]
- Clark J. T., Donachie S., Anand R., Wilson C. F., Heidrich H. G., McBride J. S. 46-53 kilodalton glycoprotein from the surface of Plasmodium falciparum merozoites. Mol Biochem Parasitol. 1989 Jan 1;32(1):15–24. doi: 10.1016/0166-6851(89)90125-4. [DOI] [PubMed] [Google Scholar]
- Creasey A., Fenton B., Walker A., Thaithong S., Oliveira S., Mutambu S., Walliker D. Genetic diversity of Plasmodium falciparum shows geographical variation. Am J Trop Med Hyg. 1990 May;42(5):403–413. doi: 10.4269/ajtmh.1990.42.403. [DOI] [PubMed] [Google Scholar]
- Devereux J., Haeberli P., Smithies O. A comprehensive set of sequence analysis programs for the VAX. Nucleic Acids Res. 1984 Jan 11;12(1 Pt 1):387–395. doi: 10.1093/nar/12.1part1.387. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Elliott J. F., Albrecht G. R., Gilladoga A., Handunnetti S. M., Neequaye J., Lallinger G., Minjas J. N., Howard R. J. Genes for Plasmodium falciparum surface antigens cloned by expression in COS cells. Proc Natl Acad Sci U S A. 1990 Aug;87(16):6363–6367. doi: 10.1073/pnas.87.16.6363. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Epping R. J., Goldstone S. D., Ingram L. T., Upcroft J. A., Ramasamy R., Cooper J. A., Bushell G. R., Geysen H. M. An epitope recognised by inhibitory monoclonal antibodies that react with a 51 kilodalton merozoite surface antigen in Plasmodium falciparum. Mol Biochem Parasitol. 1988 Feb;28(1):1–10. doi: 10.1016/0166-6851(88)90173-9. [DOI] [PubMed] [Google Scholar]
- Fenton B., Clark J. T., Wilson C. F., McBride J. S., Walliker D. Polymorphism of a 35-48 kDa Plasmodium falciparum merozoite surface antigen. Mol Biochem Parasitol. 1989 Apr;34(1):79–86. doi: 10.1016/0166-6851(89)90022-4. [DOI] [PubMed] [Google Scholar]
- Fenton B. Peptide digest studies of polymorphic proteins of Plasmodium falciparum. Mol Biochem Parasitol. 1987 May;24(1):13–22. doi: 10.1016/0166-6851(87)90111-3. [DOI] [PubMed] [Google Scholar]
- Holder A. A. The precursor to major merozoite surface antigens: structure and role in immunity. Prog Allergy. 1988;41:72–97. [PubMed] [Google Scholar]
- Jeffreys A. J., Neumann R., Wilson V. Repeat unit sequence variation in minisatellites: a novel source of DNA polymorphism for studying variation and mutation by single molecule analysis. Cell. 1990 Feb 9;60(3):473–485. doi: 10.1016/0092-8674(90)90598-9. [DOI] [PubMed] [Google Scholar]
- Jeffreys A. J., Wilson V., Thein S. L. Hypervariable 'minisatellite' regions in human DNA. Nature. 1985 Mar 7;314(6006):67–73. doi: 10.1038/314067a0. [DOI] [PubMed] [Google Scholar]
- Kemp D. J., Cowman A. F., Walliker D. Genetic diversity in Plasmodium falciparum. Adv Parasitol. 1990;29:75–149. doi: 10.1016/s0065-308x(08)60105-0. [DOI] [PubMed] [Google Scholar]
- McBride J. S., Newbold C. I., Anand R. Polymorphism of a high molecular weight schizont antigen of the human malaria parasite Plasmodium falciparum. J Exp Med. 1985 Jan 1;161(1):160–180. doi: 10.1084/jem.161.1.160. [DOI] [PMC free article] [PubMed] [Google Scholar]
- McBride J. S., Walliker D., Morgan G. Antigenic diversity in the human malaria parasite Plasmodium falciparum. Science. 1982 Jul 16;217(4556):254–257. doi: 10.1126/science.6178159. [DOI] [PubMed] [Google Scholar]
- Miettinen-Baumann A., Strych W., McBride J., Heidrich H. G. A 46,000 dalton Plasmodium falciparum merozoite surface glycoprotein not related to the 185,000-195,000 dalton schizont precursor molecule: isolation and characterization. Parasitol Res. 1988;74(4):317–323. doi: 10.1007/BF00539452. [DOI] [PubMed] [Google Scholar]
- Mullis K. B., Faloona F. A. Specific synthesis of DNA in vitro via a polymerase-catalyzed chain reaction. Methods Enzymol. 1987;155:335–350. doi: 10.1016/0076-6879(87)55023-6. [DOI] [PubMed] [Google Scholar]
- 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]
- Ramasamy R. Studies on glycoproteins in the human malaria parasite Plasmodium falciparum. Identification of a myristilated 45kDa merozoite membrane glycoprotein. Immunol Cell Biol. 1987 Oct;65(Pt 5):419–424. doi: 10.1038/icb.1987.48. [DOI] [PubMed] [Google Scholar]
- Saiki R. K., Scharf S., Faloona F., Mullis K. B., Horn G. T., Erlich H. A., Arnheim N. Enzymatic amplification of beta-globin genomic sequences and restriction site analysis for diagnosis of sickle cell anemia. Science. 1985 Dec 20;230(4732):1350–1354. doi: 10.1126/science.2999980. [DOI] [PubMed] [Google Scholar]
- Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Saul A., Lord R., Jones G., Geysen H. M., Gale J., Mollard R. Cross-reactivity of antibody against an epitope of the Plasmodium falciparum second merozoite surface antigen. Parasite Immunol. 1989 Nov;11(6):593–601. doi: 10.1111/j.1365-3024.1989.tb00923.x. [DOI] [PubMed] [Google Scholar]
- Schwarz R. T., Riveros-Moreno V., Lockyer M. J., Nicholls S. C., Davey L. S., Hillman Y., Sandhu J. S., Freeman R. R., Holder A. A. Structural diversity of the major surface antigen of Plasmodium falciparum merozoites. Mol Cell Biol. 1986 Mar;6(3):964–968. doi: 10.1128/mcb.6.3.964. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Smythe J. A., Coppel R. L., Brown G. V., Ramasamy R., Kemp D. J., Anders R. F. Identification of two integral membrane proteins of Plasmodium falciparum. Proc Natl Acad Sci U S A. 1988 Jul;85(14):5195–5199. doi: 10.1073/pnas.85.14.5195. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Smythe J. A., Peterson M. G., Coppel R. L., Saul A. J., Kemp D. J., Anders R. F. Structural diversity in the 45-kilodalton merozoite surface antigen of Plasmodium falciparum. Mol Biochem Parasitol. 1990 Mar;39(2):227–234. doi: 10.1016/0166-6851(90)90061-p. [DOI] [PubMed] [Google Scholar]
- Stanley H. A., Howard R. F., Reese R. T. Recognition of a Mr 56K glycoprotein on the surface of Plasmodium falciparum merozoites by mouse monoclonal antibodies. J Immunol. 1985 May;134(5):3439–3444. [PubMed] [Google Scholar]
- 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]
- Thaithong S., Beale G. H., Fenton B., McBride J., Rosario V., Walker A., Walliker D. Clonal diversity in a single isolate of the malaria parasite Plasmodium falciparum. Trans R Soc Trop Med Hyg. 1984;78(2):242–245. doi: 10.1016/0035-9203(84)90287-6. [DOI] [PubMed] [Google Scholar]
- 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]