Structural basis for epitope masking and strain specificity of a conserved epitope in an intrinsically disordered malaria vaccine candidate

• DOI: 10.1038/srep10103
• Publication Date: 2015-05-12T12:31:27Z
• Authors: Rodrigo A. V. Mor...; Christopher A. Ma...; Jeffrey Seow; Bankala Krishnarjuna; Nyssa Drinkwater; Romain Rouet; Robin F. Anders; Daniel Christ; Sheena McGowan; Raymond S. Norton
• Keywords: Conformational epitope

Merozoite surface protein 2 (MSP2) is an intrinsically disordered, membrane-anchored antigen of the malaria parasite Plasmodium falciparum. MSP2 can elicit a protective, albeit strain-specific, antibody response in humans. Antibodies are generated to conserved N- and C-terminal regions but many these react poorly with native on surface. Here we demonstrate that recognition N-terminal epitope by mAb 6D8 incompatible membrane-bound conformation region, suggesting mechanism which escapes recognition. Furthermore, crystal structures NMR spectroscopy identify transient, strain-specific interactions between beyond epitope. These account for differential affinity two allelic families MSP2, even though binds fully results highlight unappreciated mechanisms may modulate specificity efficacy immune responses towards disordered antigens.