Skip to main content
Immunology logoLink to Immunology
. 1998 May;94(1):28–34. doi: 10.1046/j.1365-2567.1998.00486.x

Evidence for epitope-specific thymus-independent response against a repeat sequence in a protein antigen.

N Kumar 1, H Zheng 1
PMCID: PMC1364327  PMID: 9708183

Abstract

We have studied the immunogenicity of a recombinant heat-shock protein-related stress protein of 70,000 MW (Pfhsp) of the human malaria parasite Plasmodium falciparum in H-2 congenic and non-congenic strains of inbred and outbred mice. Most mice of different genetic backgrounds produced antibodies to Pfhsp, indicating a lack of any apparent genetic restriction of immune response. A peptide corresponding to the GGMP repeat sequence in the C-terminal region of Pfhsp was recognized by more than 75% of sera from immunized mice. The GGMP repeat epitope-specific antibodies were largely of the IgM isotype, especially in all seven inbred strains of mice tested. The lack of significant boosting of the immune response, a predominantly IgM isotype of antibodies and generation of antibody responses in athymic nude mice suggest a thymus-independent response against the GGMP repeat epitope in the Pfhsp molecule.

Full text

PDF
28

Images in this article

Selected References

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

  1. Benacerraf B., Germain R. N. The immune response genes of the major histocompatibility complex. Immunol Rev. 1978;38:70–119. doi: 10.1111/j.1600-065x.1978.tb00385.x. [DOI] [PubMed] [Google Scholar]
  2. Bianco A. E., Favaloro J. M., Burkot T. R., Culvenor J. G., Crewther P. E., Brown G. V., Anders R. F., Coppel R. L., Kemp D. J. A repetitive antigen of Plasmodium falciparum that is homologous to heat shock protein 70 of Drosophila melanogaster. Proc Natl Acad Sci U S A. 1986 Nov;83(22):8713–8717. doi: 10.1073/pnas.83.22.8713. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bressan G. M., Argos P., Stanley K. K. Repeating structure of chick tropoelastin revealed by complementary DNA cloning. Biochemistry. 1987 Mar 24;26(6):1497–1503. doi: 10.1021/bi00380a001. [DOI] [PubMed] [Google Scholar]
  4. Cebra J. J., Komisar J. L., Schweitzer P. A. CH isotype 'switching' during normal B-lymphocyte development. Annu Rev Immunol. 1984;2:493–548. doi: 10.1146/annurev.iy.02.040184.002425. [DOI] [PubMed] [Google Scholar]
  5. Chang S. P., Hui G. S., Kato A., Siddiqui W. A. Generalized immunological recognition of the major merozoite surface antigen (gp195) of Plasmodium falciparum. Proc Natl Acad Sci U S A. 1989 Aug;86(16):6343–6347. doi: 10.1073/pnas.86.16.6343. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Del Giudice G., Cheng Q., Mazier D., Berbiguier N., Cooper J. A., Engers H. D., Chizzolini C., Verdini A. S., Bonelli F., Pessi A. Immunogenicity of a non-repetitive sequence of Plasmodium falciparum circumsporozoite protein in man and mice. Immunology. 1988 Feb;63(2):187–191. [PMC free article] [PubMed] [Google Scholar]
  7. Dintzis H. M., Dintzis R. Z., Vogelstein B. Molecular determinants of immunogenicity: the immunon model of immune response. Proc Natl Acad Sci U S A. 1976 Oct;73(10):3671–3675. doi: 10.1073/pnas.73.10.3671. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Good M. F., Berzofsky J. A., Maloy W. L., Hayashi Y., Fujii N., Hockmeyer W. T., Miller L. H. Genetic control of the immune response in mice to a Plasmodium falciparum sporozoite vaccine. Widespread nonresponsiveness to single malaria T epitope in highly repetitive vaccine. J Exp Med. 1986 Aug 1;164(2):655–660. doi: 10.1084/jem.164.2.655. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Höhfeld J., Minami Y., Hartl F. U. Hip, a novel cochaperone involved in the eukaryotic Hsc70/Hsp40 reaction cycle. Cell. 1995 Nov 17;83(4):589–598. doi: 10.1016/0092-8674(95)90099-3. [DOI] [PubMed] [Google Scholar]
  10. Kaufmann S. H. Heat shock proteins and the immune response. Immunol Today. 1990 Apr;11(4):129–136. doi: 10.1016/0167-5699(90)90050-j. [DOI] [PubMed] [Google Scholar]
  11. Kemp D. J., Coppel R. L., Anders R. F. Repetitive proteins and genes of malaria. Annu Rev Microbiol. 1987;41:181–208. doi: 10.1146/annurev.mi.41.100187.001145. [DOI] [PubMed] [Google Scholar]
  12. Kumar N., Syin C. A., Carter R., Quakyi I., Miller L. H. Plasmodium falciparum gene encoding a protein similar to the 78-kDa rat glucose-regulated stress protein. Proc Natl Acad Sci U S A. 1988 Sep;85(17):6277–6281. doi: 10.1073/pnas.85.17.6277. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Kumar N., Zhao Y., Graves P., Perez Folgar J., Maloy L., Zheng H. Human immune response directed against Plasmodium falciparum heat shock-related proteins. Infect Immun. 1990 May;58(5):1408–1414. doi: 10.1128/iai.58.5.1408-1414.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Lew A. M., Langford C. J., Pye D., Edwards S., Corcoran L., Anders R. F. Class II restriction in mice to the malaria candidate vaccine ring infected erythrocyte surface antigen (RESA) as synthetic peptides or as expressed in recombinant vaccinia. J Immunol. 1989 Jun 1;142(11):4012–4016. [PubMed] [Google Scholar]
  15. 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]
  16. Mazier D., Mattei D. Parasite heat-shock proteins and host responses: the balance between protection and immunopathology. Springer Semin Immunopathol. 1991;13(1):37–53. doi: 10.1007/BF01225277. [DOI] [PubMed] [Google Scholar]
  17. Mond J. J., Lees A., Snapper C. M. T cell-independent antigens type 2. Annu Rev Immunol. 1995;13:655–692. doi: 10.1146/annurev.iy.13.040195.003255. [DOI] [PubMed] [Google Scholar]
  18. Pierce R. A., Alatawi A., Deak S. B., Boyd C. D. Elements of the rat tropoelastin gene associated with alternative splicing. Genomics. 1992 Apr;12(4):651–658. doi: 10.1016/0888-7543(92)90289-5. [DOI] [PubMed] [Google Scholar]
  19. Prescott N., Stowers A. W., Cheng Q., Bobogare A., Rzepczyk C. M., Saul A. Plasmodium falciparum genetic diversity can be characterised using the polymorphic merozoite surface antigen 2 (MSA-2) gene as a single locus marker. Mol Biochem Parasitol. 1994 Feb;63(2):203–212. doi: 10.1016/0166-6851(94)90056-6. [DOI] [PubMed] [Google Scholar]
  20. Rothbard J. B., Taylor W. R. A sequence pattern common to T cell epitopes. EMBO J. 1988 Jan;7(1):93–100. doi: 10.1002/j.1460-2075.1988.tb02787.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Rénia L., Mattei D., Goma J., Pied S., Dubois P., Miltgen F., Nüssler A., Matile H., Menégaux F., Gentilini M. A malaria heat-shock-like determinant expressed on the infected hepatocyte surface is the target of antibody-dependent cell-mediated cytotoxic mechanisms by nonparenchymal liver cells. Eur J Immunol. 1990 Jul;20(7):1445–1449. doi: 10.1002/eji.1830200706. [DOI] [PubMed] [Google Scholar]
  22. 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]
  23. Uparanukraw P., Toyoshima T., Aikawa M., Kumar N. Molecular cloning and localization of an abundant novel protein of Plasmodium berghei. Mol Biochem Parasitol. 1993 Jun;59(2):223–234. doi: 10.1016/0166-6851(93)90220-r. [DOI] [PubMed] [Google Scholar]
  24. Wiser M. F., Jennings G. J., Lockyer J. M., van Belkum A., van Doorn L. J. Chaperonin-like repeats in a 34-kDa Plasmodium berghei phosphoprotein. Parasitol Res. 1995;81(2):167–169. doi: 10.1007/BF00931625. [DOI] [PubMed] [Google Scholar]
  25. Yang Y. F., Tan-ariya P., Sharma Y. D., Kilejian A. The primary structure of a Plasmodium falciparum polypeptide related to heat shock proteins. Mol Biochem Parasitol. 1987 Nov;26(1-2):61–67. doi: 10.1016/0166-6851(87)90130-7. [DOI] [PubMed] [Google Scholar]
  26. Young R. A. Stress proteins and immunology. Annu Rev Immunol. 1990;8:401–420. doi: 10.1146/annurev.iy.08.040190.002153. [DOI] [PubMed] [Google Scholar]

Articles from Immunology are provided here courtesy of British Society for Immunology

RESOURCES