Identification of binding domains on red blood cell glycophorins for Babesia divergens

Authors

  • Jeny R. Cursino-Santos,

    1. Department of Blood-Borne Parasites, Lindsley Kimball Research Institute, New York Blood Center, New York, New York
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  • Greg Halverson,

    1. Core Monoclonal Antibody Facility, Lindsley Kimball Research Institute, New York Blood Center, New York, New York
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  • Marilis Rodriguez,

    1. Department of Blood-Borne Parasites, Lindsley Kimball Research Institute, New York Blood Center, New York, New York
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  • Mohandas Narla,

    1. Red Cell Physiology Laboratory, Lindsley Kimball Research Institute, New York Blood Center, New York, New York
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  • Cheryl A. Lobo

    Corresponding author
    1. Department of Blood-Borne Parasites, Lindsley Kimball Research Institute, New York Blood Center, New York, New York
    • Address reprint requests to: Cheryl A. Lobo, Department of Blood-Borne Parasites, Lindsley Kimball Research Institute, New York Blood Center, New York, NY 10065; e-mail: clobo@nybloodcenter.org.

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  • Funding for this study was provided by a grant from the NIH to CAL, RO1-HL105694.

Abstract

Background

Invasion of red blood cells (RBCs) is one of the critical points in the lifecycle of Babesia. The parasite does not invade other host cells. Earlier work has shown that GPA and GPB function as putative receptors during parasite invasion. The primary focus of this study was the delineation of parasite-binding domains on GPA and GPB.

Study Design and Methods

The assay of choice to validate molecules that participate in invasion is an inhibition of invasion assay, in which changes in parasitemia are assessed relative to a wild-type assay (no inhibitors). Inhibition of invasion can be achieved by modification of different components of the assay or by the addition of competitors of the molecules that participate in invasion. In this study purified antibody fragments to various domains on GPA and GPB were tested for magnitude of inhibition of parasite invasion. Effects on invasion were monitored by assessment of Giemsa-stained smears every 24 hours.

Results

Among 10 selected antibodies directed at various epitopes on GPA and GPB, antibodies directed against GPAM epitopes had the most severe effect (up to 35%) on inhibition of invasion, followed by antibodies directed against GPBS epitope (up to 24%).

Conclusion

This study confirms the role of RBC glycophorins A and B in Babesia divergens invasion and shows that the GPAM and GPBS epitopes are likely to play an important role in the entry process.

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