Suarez C E, Florin-Christensen M, Hines S A, Palmer G H, Brown W C, McElwain T F
Program in Vector-Borne Diseases, Animal Disease Research Unit, Agricultural Research Service, U.S. Department of Agriculture, Washington 99164, USA.
Infect Immun. 2000 Dec;68(12):6865-70. doi: 10.1128/IAI.68.12.6865-6870.2000.
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 gene 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 epitopes 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.
牛巴贝斯虫裂殖子表面抗原1（MSA-1）是可变裂殖子表面抗原（VMSA）家族的成员，是一种免疫显性糖蛋白，可引发抑制红细胞入侵的抗体。虽然抗原多态性是vmsa基因的普遍特征，但msa-1序列多态性的分子基础和程度尚未得到充分表征。在本研究中，我们确定了牛巴贝斯虫生物学克隆的墨西哥Mo7株中的msa-1基因座，并鉴定了MSA-1抗原性不同菌株之间的序列差异。然后，我们确定不同msa-1等位基因之间保守的序列是否会诱导交叉反应性CD4(+) T淋巴细胞或抑制性抗体。Mo7中的msa-1基因座包含一个单一的msa-1基因，两侧是转录基因，与VMSA基因家族成员没有序列同源性。阿根廷牛巴贝斯虫菌株R1A和S2P的msa-1基因的氨基酸序列彼此98.8%相同，抗S2P MSA-1的抗体与天然R1A MSA-1交叉反应。相比之下，阿根廷和墨西哥Mo7 msa-1等位基因之间的同一性仅为52%，没有连续超过16个氨基酸的相同序列。尽管序列保守性有限，但抗R1A MSA-1的抗体能够抑制Mo7裂殖子对红细胞的入侵。结果表明，尽管墨西哥和阿根廷菌株等位基因之间存在显著的序列差异，但抑制敏感表位是保守的，这支持了多态性MSA-1在红细胞入侵中具有保守的功能作用。
