Characterization of allelic variation in the Babesia bovis merozoite surface antigen 1 (MSA-1) locus and identification of a cross-reactive inhibition-sensitive MSA-1 epitope

The Babesia bovis merozoite surface antigen 1 (MSA-1), a member of the vari able merozoite surface antigen (VMSA) family, is an immunodominant glycopro tein which elicits antibodies that inhibit erythrocyte invasion. While anti genic 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 c onserved between distinct msa-1 alleles would induce cross-reactive CD4(+) T lymphocytes or inhibitory antibodies. The msa-1 locus in Mo7 contains a s ingle msa-1 gene flanked by transcribed genes,vith no sequence homology to members of the VMSA gene family. Argentina B. bovis strains R1A and S2P hav e msa-1 genes with amino acid sequences that are 98.8% identical to each ot her, 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 o nly 52%, with no continuous stretch of identity longer then 16 amino acids. Despite limited sequence conservation, antibodies against R1A MSA-1 were a ble to inhibit invasion of erythrocytes by Mo7 merozoites. The results indi cate that inhibition-sensitive epitopes are conserved despite significant s equence divergence between Mexico and Argentina strain alleles and support a conserved functional role for polymorphic MSA-1 in erythrocyte invasion.