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. 1996 Mar;64(3):1054–1059. doi: 10.1128/iai.64.3.1054-1059.1996

Identification of T-cell determinants in natural immune responses to the Plasmodium falciparum apical membrane antigen (AMA-1) in an adult population exposed to malaria.

A A Lal 1, M A Hughes 1, D A Oliveira 1, C Nelson 1, P B Bloland 1, A J Oloo 1, W E Hawley 1, A W Hightower 1, B L Nahlen 1, V Udhayakumar 1
PMCID: PMC173881  PMID: 8641760

Abstract

AMA-1 of Plasmodium falciparum is a promising candidate antigen in malaria vaccine development. In this study, we have mapped the immunodominant T-cell determinants in this antigen by using synthetic peptides. From the amphipathic scores, 17 putative T-cell determinants were identified. Nine of the 17 peptides complementary to the putative T-cell determinants induced proliferation of peripheral blood mononuclear cells (PBMC) from Kenyan residents who had lifelong exposure to malaria; none of these peptides induced proliferation of PBMC from donors who were not previously exposed to malaria. This indicates that AMA-1 peptides were stimulating T cells that were previously primed by prior exposure to P. falciparum. Many positive responders showed reactivity to more than one peptide, and some of the potent proliferative T epitopes were found to be localized in the highly conserved regions of AMA-1, suggesting that it may be possible to induce T-cell memory that can recognize different variant forms of the parasite. This information on the natural immune responses against the AMA-1 vaccine antigen in clinically immune adults will be helpful in the development of an AMA-1 antigen-based malaria vaccine and may also guide testing of AMA-1-based vaccine formulations.

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Selected References

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  1. Beier J. C., Perkins P. V., Onyango F. K., Gargan T. P., Oster C. N., Whitmire R. E., Koech D. K., Roberts C. R. Characterization of malaria transmission by Anopheles (Diptera: Culicidae) in western Kenya in preparation for malaria vaccine trials. J Med Entomol. 1990 Jul;27(4):570–577. doi: 10.1093/jmedent/27.4.570. [DOI] [PubMed] [Google Scholar]
  2. Cheng Q., Saul A. Sequence analysis of the apical membrane antigen I (AMA-1) of Plasmodium vivax. Mol Biochem Parasitol. 1994 May;65(1):183–187. doi: 10.1016/0166-6851(94)90127-9. [DOI] [PubMed] [Google Scholar]
  3. Collins W. E., Pye D., Crewther P. E., Vandenberg K. L., Galland G. G., Sulzer A. J., Kemp D. J., Edwards S. J., Coppel R. L., Sullivan J. S. Protective immunity induced in squirrel monkeys with recombinant apical membrane antigen-1 of Plasmodium fragile. Am J Trop Med Hyg. 1994 Dec;51(6):711–719. doi: 10.4269/ajtmh.1994.51.711. [DOI] [PubMed] [Google Scholar]
  4. Crewther P. E., Culvenor J. G., Silva A., Cooper J. A., Anders R. F. Plasmodium falciparum: two antigens of similar size are located in different compartments of the rhoptry. Exp Parasitol. 1990 Feb;70(2):193–206. doi: 10.1016/0014-4894(90)90100-q. [DOI] [PubMed] [Google Scholar]
  5. Deans J. A., Alderson T., Thomas A. W., Mitchell G. H., Lennox E. S., Cohen S. Rat monoclonal antibodies which inhibit the in vitro multiplication of Plasmodium knowlesi. Clin Exp Immunol. 1982 Aug;49(2):297–309. [PMC free article] [PubMed] [Google Scholar]
  6. Deans J. A., Knight A. M., Jean W. C., Waters A. P., Cohen S., Mitchell G. H. Vaccination trials in rhesus monkeys with a minor, invariant, Plasmodium knowlesi 66 kD merozoite antigen. Parasite Immunol. 1988 Sep;10(5):535–552. doi: 10.1111/j.1365-3024.1988.tb00241.x. [DOI] [PubMed] [Google Scholar]
  7. Doolan D. L., Beck H. P., Good M. F. Evidence for limited activation of distinct CD4+ T cell subsets in response to the Plasmodium falciparum circumsporozoite protein in Papua New Guinea. Parasite Immunol. 1994 Mar;16(3):129–136. doi: 10.1111/j.1365-3024.1994.tb00332.x. [DOI] [PubMed] [Google Scholar]
  8. Engelhard V. H. Structure of peptides associated with class I and class II MHC molecules. Annu Rev Immunol. 1994;12:181–207. doi: 10.1146/annurev.iy.12.040194.001145. [DOI] [PubMed] [Google Scholar]
  9. Greenwood B., Marsh K., Snow R. Why do some African children develop severe malaria? Parasitol Today. 1991 Oct;7(10):277–281. doi: 10.1016/0169-4758(91)90096-7. [DOI] [PubMed] [Google Scholar]
  10. Ho M., Webster H. K., Looareesuwan S., Supanaranond W., Phillips R. E., Chanthavanich P., Warrell D. A. Antigen-specific immunosuppression in human malaria due to Plasmodium falciparum. J Infect Dis. 1986 Apr;153(4):763–771. doi: 10.1093/infdis/153.4.763. [DOI] [PubMed] [Google Scholar]
  11. Kremsner P. G., Zotter G. M., Feldmeier H., Graninger W., Rocha R. M., Jansen-Rosseck R., Bienzle U. Immune response in patients during and after Plasmodium falciparum infection. J Infect Dis. 1990 May;161(5):1025–1028. doi: 10.1093/infdis/161.5.1025. [DOI] [PubMed] [Google Scholar]
  12. Lockyer M. J., Marsh K., Newbold C. I. Wild isolates of Plasmodium falciparum show extensive polymorphism in T cell epitopes of the circumsporozoite protein. Mol Biochem Parasitol. 1989 Dec;37(2):275–280. doi: 10.1016/0166-6851(89)90159-x. [DOI] [PubMed] [Google Scholar]
  13. Margalit H., Spouge J. L., Cornette J. L., Cease K. B., Delisi C., Berzofsky J. A. Prediction of immunodominant helper T cell antigenic sites from the primary sequence. J Immunol. 1987 Apr 1;138(7):2213–2229. [PubMed] [Google Scholar]
  14. Marshall V. M., Peterson M. G., Lew A. M., Kemp D. J. Structure of the apical membrane antigen I (AMA-1) of Plasmodium chabaudi. Mol Biochem Parasitol. 1989 Dec;37(2):281–283. doi: 10.1016/0166-6851(89)90160-6. [DOI] [PubMed] [Google Scholar]
  15. Moreno A., Clavijo P., Edelman R., Davis J., Sztein M., Sinigaglia F., Nardin E. CD4+ T cell clones obtained from Plasmodium falciparum sporozoite-immunized volunteers recognize polymorphic sequences of the circumsporozoite protein. J Immunol. 1993 Jul 1;151(1):489–499. [PubMed] [Google Scholar]
  16. Peterson M. G., Marshall V. M., Smythe J. A., Crewther P. E., Lew A., Silva A., Anders R. F., Kemp D. J. Integral membrane protein located in the apical complex of Plasmodium falciparum. Mol Cell Biol. 1989 Jul;9(7):3151–3154. doi: 10.1128/mcb.9.7.3151. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Peterson M. G., Nguyen-Dinh P., Marshall V. M., Elliott J. F., Collins W. E., Anders R. F., Kemp D. J. Apical membrane antigen of Plasmodium fragile. Mol Biochem Parasitol. 1990 Mar;39(2):279–283. doi: 10.1016/0166-6851(90)90067-v. [DOI] [PubMed] [Google Scholar]
  18. Quakyi I. A., Currier J., Fell A., Taylor D. W., Roberts T., Houghten R. A., England R. D., Berzofsky J. A., Miller L. H., Good M. F. Analysis of human T cell clones specific for conserved peptide sequences within malaria proteins. Paucity of clones responsive to intact parasites. J Immunol. 1994 Sep 1;153(5):2082–2092. [PubMed] [Google Scholar]
  19. Schofield L., Uadia P. Lack of Ir gene control in the immune response to malaria. I. A thymus-independent antibody response to the repetitive surface protein of sporozoites. J Immunol. 1990 Apr 1;144(7):2781–2788. [PubMed] [Google Scholar]
  20. Shi Y. P., Alpers M. P., Povoa M. M., Lal A. A. Diversity in the immunodominant determinants of the circumsporozoite protein of Plasmodium falciparum parasites from malaria-endemic regions of Papua New Guinea and Brazil. Am J Trop Med Hyg. 1992 Dec;47(6):844–851. doi: 10.4269/ajtmh.1992.47.844. [DOI] [PubMed] [Google Scholar]
  21. 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]
  22. Thomas A. W., Deans J. A., Mitchell G. H., Alderson T., Cohen S. The Fab fragments of monoclonal IgG to a merozoite surface antigen inhibit Plasmodium knowlesi invasion of erythrocytes. Mol Biochem Parasitol. 1984 Oct;13(2):187–199. doi: 10.1016/0166-6851(84)90112-9. [DOI] [PubMed] [Google Scholar]
  23. Thomas A. W., Waters A. P., Carr D. Analysis of variation in PF83, an erythrocytic merozoite vaccine candidate antigen of Plasmodium falciparum. Mol Biochem Parasitol. 1990 Sep-Oct;42(2):285–287. doi: 10.1016/0166-6851(90)90172-i. [DOI] [PubMed] [Google Scholar]
  24. Udhayakumar V., Anyona D., Kariuki S., Shi Y. P., Bloland P. B., Branch O. H., Weiss W., Nahlen B. L., Kaslow D. C., Lal A. A. Identification of T and B cell epitopes recognized by humans in the C-terminal 42-kDa domain of the Plasmodium falciparum merozoite surface protein (MSP)-1. J Immunol. 1995 Jun 1;154(11):6022–6030. [PubMed] [Google Scholar]
  25. Udhayakumar V., Shi Y. P., Kumar S., Jue D. L., Wohlhueter R. M., Lal A. A. Antigenic diversity in the circumsporozoite protein of Plasmodium falciparum abrogates cytotoxic-T-cell recognition. Infect Immun. 1994 Apr;62(4):1410–1413. doi: 10.1128/iai.62.4.1410-1413.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Waters A. P., Thomas A. W., Deans J. A., Mitchell G. H., Hudson D. E., Miller L. H., McCutchan T. F., Cohen S. A merozoite receptor protein from Plasmodium knowlesi is highly conserved and distributed throughout Plasmodium. J Biol Chem. 1990 Oct 15;265(29):17974–17979. [PubMed] [Google Scholar]
  27. Zevering Y., Amante F., Smillie A., Currier J., Smith G., Houghten R. A., Good M. F. High frequency of malaria-specific T cells in non-exposed humans. Eur J Immunol. 1992 Mar;22(3):689–696. doi: 10.1002/eji.1830220311. [DOI] [PubMed] [Google Scholar]
  28. de la Cruz V. F., Lal A. A., McCutchan T. F. Sequence variation in putative functional domains of the circumsporozoite protein of Plasmodium falciparum. Implications for vaccine development. J Biol Chem. 1987 Sep 5;262(25):11935–11939. [PubMed] [Google Scholar]
  29. de la Cruz V. F., Maloy W. L., Miller L. H., Lal A. A., Good M. F., McCutchan T. F. Lack of cross-reactivity between variant T cell determinants from malaria circumsporozoite protein. J Immunol. 1988 Oct 1;141(7):2456–2460. [PubMed] [Google Scholar]

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