Fine Specificity of Plasmodium vivax Duffy Binding Protein Binding Engagement of the Duffy Antigen on Human Erythrocytes
| Autor: | Asim A. Siddiqui, Francis B. Ntumngia, Michael Foley, Joanne L. Casey, Jia Xainli, Jesse Schloegel, Lenore L. Carias, Menachem Shoham, John H. Adams, Christopher L. King |
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| Rok vydání: | 2012 |
| Předmět: |
Models
Molecular Protein Folding Erythrocytes Protein Conformation medicine.drug_class Immunology Plasmodium vivax Protozoan Proteins Antibodies Protozoan Antigens Protozoan Receptors Cell Surface Monoclonal antibody Microbiology Protein structure Antigen medicine Animals Humans Binding site Antiserum Binding Sites biology Binding protein Antibodies Monoclonal biology.organism_classification Molecular biology Protein Structure Tertiary Rats Retraction Infectious Diseases Gene Expression Regulation Parasitology Fungal and Parasitic Infections Duffy Blood-Group System Binding domain |
| Zdroj: | Infection and Immunity. 80:2920-2928 |
| ISSN: | 1098-5522 0019-9567 |
| DOI: | 10.1128/iai.00206-12 |
| Popis: | Plasmodium vivax invasion of human erythrocytes requires interaction of the P. vivax Duffy binding protein (PvDBP) with its host receptor, the Duffy antigen (Fy) on the erythrocyte surface. Consequently, PvDBP is a leading vaccine candidate. The binding domain of PvDBP lies in a cysteine-rich portion of the molecule called region II (PvDBPII). PvDBPII contains three distinct subdomains based upon intramolecular disulfide bonding patterns. Subdomain 2 (SD2) is highly polymorphic and is thought to contain many key residues for binding to Fy, while SD1 and SD3 are comparatively conserved and their role in Fy binding is not well understood. To examine the relative contributions of the different subdomains to binding to Fy and their abilities to elicit strain-transcending binding-inhibitory antibodies, we evaluated recombinant proteins from SD1+2, SD2, SD3, and SD3+, which includes 24 residues of SD2. All of the recombinant subdomains, except for SD2, bound variably to human erythrocytes, with constructs containing SD3 showing the best binding. Antisera raised in laboratory animals against SD3, SD3+, and SD2+3 inhibited the binding of full-length PvDBPII, which is strain transcending, whereas antisera generated to SD1+2 and SD2 failed to generate blocking antibodies. All of the murine monoclonal antibodies generated to full-length PvDBPII that had significant binding-inhibitory activity recognized only SD3. Thus, SD3 binds Fy and elicits blocking antibodies, indicating that it contains residues critical to Fy binding that could be the basis of a strain-transcending candidate vaccine against P. vivax . |
| Databáze: | OpenAIRE |
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