Submitted to: Conference Research Workers Disease Meeting
Publication Type: Proceedings
Publication Acceptance Date: 4/25/2000
Publication Date: 11/1/2000
Citation: Suarez, C.E., Florin-Christense, M., Hines, S., Palmer, G., Brown, W., Mcelwain, T. 2000. Characterization of allelic variation in the babesia bovis merozoite surface antigen-1 locus (msa-1). Conference Research Workers Disease Meeting.
Interpretive Summary: In this work we define the locus structure of the gene encoding for the major merozoite surface antigen-1 of Babesia bovis. We defined conserved areas of the molecule that can be used to elicit antibodies that are able to neutralize invation of the erythrocyte by the parasite. Molecular definition of these conserved regions might help for the design of improved subunit vaccines
Technical Abstract: The Babesia bovis merozoite surface antigen-1 (MSA-1), a member of the Variable Merozoite Surface Antigen (VMSA) family, is an immunodominant glycoprotein which elicits antibodies that inhibit erythrocyte invasion. While antigenic polymorphism is a general feature of vmsa genes, the molecular basis and extent of msa-1 sequence polymorphism have not been well characterized. In this study we defined the msa-1 locus in the biologically cloned Mexico Mo7 strain of B. bovis, and identified the sequence differences between MSA-1 antigenically dissimilar strains. We then determined whether sequences conserved between distinct msa-1 alleles would induce cross-reactive CD4+ T lymphocytes or inhibitory antibodies. The msa-1 locus in Mo7 contains a single msa-1 gene flanked by transcribed genes with no sequence homology to members of the vmsa family. Argentina B. bovis strains R1A and S2P have msa-1 genes with amino acid sequences that are 98.8% identical to each other, and antibodies against S2P MSA-1 cross-react with native R1A MSA-1. In contrast, identity between the Argentina and Mexico Mo7 msa-1 alleles is only 52%, with no continuous stretch of identity longer than 16 amino acids. Despite limited sequence conservation, antibodies against R1A MSA-1 were able to inhibit invasion of erythrocytes by Mo7 merozoites. The results indicate that inhibition-sensitive epitope(s) are conserved despite significant sequence divergence between Mexico and Argentina strain alleles, and support a conserved functional role for polymorphic MSA-1 in erythrocyte invasion.