Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Rapid switching to multiple antigenic and adhesive phenotypes in malaria


ADHESION of parasitized erythrocytes to post-capillary venular endothelium1or uninfected red cells'2–4 is strongly implicated in the pathogenesis of severe Plasmodlum faldparum malaria. Neo-antigens at the infected red-cell surface adhere to a variety of host receptors5–9, demonstrate serological diversity in field isolates10,11 and may also be a target of the host-protective immune response12. Here we use sequential cloning ofP. faldparum by micromanipula-tion to investigate the ability of a parasite to switch antigenic and cytoadherence phenotypes. Our data show that antigens at the parasitized cell surface undergo clonal variation in vitro in the absence of immune pressure at the rate of 2% per generation with concomitant modulations of the adhesive phenotype. A clone has the potential to switch at high frequency to a variety of antigenic and adhesive phenotypes, including a new type of cytoadherence behaviour, 'auto-agglutination' of infected erythrocytes. This rapid appearance of antigenic and functional heterogeneity has important implications for pathogenesis and acquired immunity.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.


  1. 1

    MacPherson, G. G., Warrell, M. J., White, N. J., Looareesuran, S. & Warrell, D. A. Am. J. Path. 119, 385–401 (1985).

    CAS  PubMed  Google Scholar 

  2. 2

    David, P. H., Handunetti, S. M., Leech, J. H., Gamage, P. & Mendis, K. M. Am. J. trop. Med. Hyg. 38, 289–297 (1988).

    CAS  Article  Google Scholar 

  3. 3

    Udomsangpetch, R. et al. J. exp. Med. 169, 1835–1840 (1989).

    CAS  Article  Google Scholar 

  4. 4

    Carlson, J. et al. Lancet 336, 1457–1460 (1990).

    CAS  Article  Google Scholar 

  5. 5

    Barnwell, J. W. et al. J. clin. Invest. 84, 765–772 (1989).

    CAS  Article  Google Scholar 

  6. 6

    Ockenhouse, C. F., Tandon, N. N., Magowan, C., Jamieson, G. A. & Chulay, J. D. Science 243, 1469–1471 (1989).

    ADS  CAS  Article  Google Scholar 

  7. 7

    Oquendo, P., Hundt, E., Lawler, J. & Seed, B. Cell 58, 95–101 (1989).

    CAS  Article  Google Scholar 

  8. 8

    Roberts, D. D. et al. Nature 318, 64–66 (1985).

    ADS  CAS  Article  Google Scholar 

  9. 9

    Berendt, A. R., Simmons, D. L., Tansey, J., Newbold, C. I. & Marsh, K. Nature 341, 57–59 (1989).

    ADS  CAS  Article  Google Scholar 

  10. 10

    Marsh, K. & Howard, R. J. Science 231, 150–153 (1986).

    ADS  CAS  Article  Google Scholar 

  11. 11

    Forsyth, K. P. et al. Am. J. trop. Med. Hyg. 41, 259–267 (1989).

    CAS  Article  Google Scholar 

  12. 12

    Marsh, K., Otoo, L., Hayes, R. J., Carson, D. C. & Greenwood, B. M. Trans. R. Soc. trop. Med. 83, 293–303 (1989).

    CAS  Article  Google Scholar 

  13. 13

    Sinnis, P. & Wellems, T. E. Genomics 3, 287–295 (1988).

    CAS  Article  Google Scholar 

  14. 14

    Turner, C. M. R. & Barry, J. D. Parasitology 99, 67–75 (1989).

    Article  Google Scholar 

  15. 15

    Borst, P. & Greaves, D. R. Science 235, 658–667 (1987).

    ADS  CAS  Article  Google Scholar 

  16. 16

    Brown, K. N. & Brown, I. N. Nature 208, 1286–1288 (1965).

    ADS  CAS  Article  Google Scholar 

  17. 17

    Barnwell, J. R., Howard, R. J., Coon, H. G. & Miller, L. H. Infect. Immun. 40, 985–994 (1983).

    CAS  PubMed  PubMed Central  Google Scholar 

  18. 18

    McLean, S. A., Pearson, C. D. & Phillips, R. S. Expl Parasitol. 54, 296–302 (1986).

    Article  Google Scholar 

  19. 19

    Handunnetti, S. M., Mendis, K. N. & David, P. D. J. exp. Med. 165, 1269–1283 (1987).

    CAS  Article  Google Scholar 

  20. 20

    Gilks, C. F., Walliker, D. & Newbold, C. I. Parasite Immun. 12, 45–64 (1990).

    CAS  Article  Google Scholar 

  21. 21

    Biggs, B. A. et al. Proc. natn. Acad. Sci. U.S.A. 88, 9171–9174 (1991).

    ADS  CAS  Article  Google Scholar 

  22. 22

    Baird, J. K. et al. Am. J. trop. Med. Hyg. 45, 65–76 (1991).

    CAS  Article  Google Scholar 

  23. 23

    Leech, J. H., Barnwell, J. W., Miller, L. H. & Howard, R. J. J. exp. Med. 159, 1567–1575 (1984).

    CAS  Article  Google Scholar 

  24. 24

    Magowan, C., Woolish, W., Anderson, L. & Leech, J. J. exp. Med. 168, 1307–1319 (1988).

    CAS  Article  Google Scholar 

  25. 25

    Trager, W. & Jensen, J. B. Science 193, 673–675 (1976).

    ADS  CAS  Article  Google Scholar 

  26. 26

    Haynes, J. D., Diggs, C. L., Hines, F. A. & Desjardins, R. E. Nature 263, 767–769 (1976).

    ADS  CAS  Article  Google Scholar 

  27. 27

    Jensen, J. B. Am. J. trop. Med. Hyg. 27, 1274–1280 (1978).

    CAS  Article  Google Scholar 

  28. 28

    Tandon, N. N., Lipsky, R. H., Burgess, W. H. & Jamieson, G. A. J. biol. Chem. 264, 7570–7575 (1989).

    CAS  PubMed  Google Scholar 

  29. 29

    Berendt, A. R. et al. Cell 68, 71–81 (1992).

    CAS  Article  Google Scholar 

  30. 30

    Biggs, B. A. et al. J. Immun. (in the press).

Download references

Author information



Rights and permissions

Reprints and Permissions

About this article

Cite this article

Roberts, D., Craig, Berendt, A. et al. Rapid switching to multiple antigenic and adhesive phenotypes in malaria. Nature 357, 689–692 (1992).

Download citation

Further reading


By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.


Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing