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Comparative analysis of the Plasmodium falciparum histidine-rich proteins HRP-I, HRP-II and HRP-III in malaria parasites of diverse origin

Published online by Cambridge University Press:  06 April 2009

E. P. Rock ,
K. Marsh ,
A. J. Saul ,
T. E. Wellems ,
Diane W. Taylor ,
W. L. Maloy  and
R. J. Howard
E. P. Rock
Affiliation:
Howard Hughes Medical Institute, Bethesda, Maryland 20814, USA
K. Marsh
Affiliation:
Medical Research Council Laboratories, Fajara, GM
A. J. Saul
Affiliation:
Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA
T. E. Wellems
Affiliation:
Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA
Diane W. Taylor
Affiliation:
Department of Biology, Georgetown University, Washington, D.C. 20057, USA
W. L. Maloy
Affiliation:
Laboratory of Immunogenetics, National Institute of Allergy and Infectious Disease, National Institutes of Health
R. J. Howard*
Affiliation:
Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA
*
*Reprint requests to: Dr Russell J. Howard, NIH, Building 5, Room 112, Bethesda, Maryland 20892, USA.
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Summary

Plasmodium falciparum-infected erythrocytes (IRBC) synthesize 3 histidine-rich proteins: HRP-I or the knob-associated HRP, HRP-II and HRP-III or SHARP. In order to distinguish these proteins immunochemically we prepared monoclonal antibodies which react with HRP-I, HRP-II and HRP-III, and rabbit antisera against synthetic peptides derived from the HRP-II and HRP-III sequences. A comparative analysis of diverse P. falciparum parasites was made using these antibodies and immunoprecipitation or Western blotting. HRP-I (Mr 80000–115000) was identified in all knob-positive P. falciparum parasites including isolates examined directly from Gambian patients. However, this protein was of lower abundance in these isolates and in 6 knob-positive, culture-adapted parasites compared to Aotus monkey-adapted parasites or culture-adapted parasites studied previously. HRP-II (Mr 60000–105000) was identified in all P. falciparum parasites regardless of knob-phenotype, and was recovered from culture supernatants as a secreted water-soluble protein. Within IRBC, HRP-II was found as a complex of several closely spaced bands. Cell surface radio-iodination of IRBC from several isolates and immunoprecipitation with a rabbit antiserum against the HRP-II repeat sequence identified HRP-II as a surface-exposed protein. Like HRP-I, the abundance of HRP-II was lower in the Gambian isolates than with Aotus monkey-adapted parasites studied earlier. Neither HRP-I nor HRP-II were identified in a knob-positive isolate of P. malariae collected from a Gambian patient. Analogues of these HRP were also absent from asexual parasites of diverse primate and murine malaria species screened with this panel of antibodies. HRP-III (Mr 40000–55000) was distinguished by its lower apparent size and by specific reaction with rabbit antibody against its 5-mer repeat sequence. HRP-III was of lowest abundance compared with the other two HRP. These antibody reagents and distinguishing properties should prove useful in studies on the separate functions of the 3 P. falciparum HRP.

Type
Research Article
Information
Parasitology , Volume 95 , Issue 2 , October 1987 , pp. 209 - 227
Copyright
Copyright © Cambridge University Press 1987

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