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Infection and Immunity, April 2009, p. 1689-1699, Vol. 77, No. 4
0019-9567/09/$08.00+0     doi:10.1128/IAI.01331-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Polymorphisms in Erythrocyte Binding Antigens 140 and 181 Affect Function and Binding but Not Receptor Specificity in Plasmodium falciparum{triangledown} ,{dagger}

Alexander G. Maier,1 Jake Baum,1 Brian Smith,1 David J. Conway,2 and Alan F. Cowman1*

The Walter and Eliza Hall Institute of Medical Research, Melbourne 3050, Australia,1 The London School of Hygiene and Tropical Medicine, London, United Kingdom2

Received 31 October 2008/ Returned for modification 14 December 2008/ Accepted 28 January 2009

Invasion of human erythrocytes by the malaria parasite Plasmodium falciparum utilizes multiple ligand-receptor interactions involving erythrocyte receptors and parasite erythrocyte binding proteins of the Duffy binding-like family. Erythrocyte binding antigen 175 (EBA-175) binds to glycophorin A, the most abundant protein on the human erythrocyte surface and EBA-140 (also known as BAEBL) binds to glycophorin C, while the receptor for EBA-181 (also known as JESEBL) remains unknown. EBA binding is mediated via region II, a highly structured extracellular domain that shows a degree of sequence variability between different laboratory strains/isolates. Here, we determined the influence of region II polymorphisms on host cell receptor binding and overall function during invasion of EBA-140, EBA-175, and EBA-181. Polymorphisms in the binding domains of EBA-140 and EBA-181 have been suggested previously to alter their respective receptor specificities. In our hands, these polymorphisms affected the levels of EBA-140 and EBA-181 binding to receptors but, critically, not the receptor specificities of these proteins. The degree of EBA-140 binding to glycophorin C correlates with the level of function for this ligand-receptor interaction in merozoite invasion. In contrast, EBA-175, which is highly polymorphic in region II, shows no variability in its ability to bind to its receptor, glycophorin A. Combined, these data highlight the importance of sequence variability in EBAs as driven by immune selection but not by receptor specificity.

* Corresponding author. Mailing address: The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Melbourne 3050, Australia. Phone: 61-3-93452555. Fax: 61-3-93470852. E-mail: cowman{at}wehi.edu.au

{triangledown} Published ahead of print on 9 February 2009.

{dagger} Supplemental material for this article may be found at http://iai.asm.org/.

Editor: W. A. Petri, Jr.

Infection and Immunity, April 2009, p. 1689-1699, Vol. 77, No. 4
0019-9567/09/$08.00+0     doi:10.1128/IAI.01331-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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