Antigenic variation of Anaplasma marginale: Major surface protein 2 diversity during cyclic transmission between ticks and cattle

The rickettsial pathogen Anaplasma marginale expresses a variable immunodom inant outer membrane protein, major surface protein 2 (MSP2), involved in a ntigenic variation and long-term persistence of the organism in carrier ani mals, MSP2 contains a central hypervariable region of about 100 amino acids that encodes immunogenic B-cell epitopes that induce variant-specific anti bodies during infection. Previously, we have shown that MSP2 is encoded on a polycistronic mRNA transcript in erythrocyte stages of A. marginale and d efined the structure of the genomic expression site for this transcript. In this study, we show that the same expression site is utilized in stages of R marginale infecting tick salivary glands, We also analyzed the variabili ty of this genomic expression site in Oklahoma strain A, marginale transmit ted from in vitro cultures to cattle and between cattle and ticks. The stru cture of the expression site and flanking regions was conserved except far sequence that encoded the MSP2 hypervariable region. At least three differe nt MSP2 variants were encoded in each A. marginale population. The major se quence variants did not change on passage of A, marginale between culture, acute erythrocyte stage infections, and tick salivary glands but did change during persistent infections of cattle. The variant types found in tick sa livary glands most closely resembled those present in bovine blood at the t ime of acquisition of infection, whether infection was acquired from an acu te or from a persistent rickettsemia, These variations in structure of an e xpression site for a major, immunoprotective outer membrane protein have im portant implications for vaccine development and for obtaining an improved understanding of the mechanisms of persistence of ehrlichial infections in humans, domestic animals, and reservoir hosts.