The rickettsial pathogen Anaplasma marginale expresses a variable immunodominant 
outer membrane protein, major surface protein 2 (MSP2), involved in antigenic 
variation and long-term persistence of the organism in carrier animals. MSP2 
contains a central hypervariable region of about 100 amino acids that encodes 
immunogenic B-cell epitopes that induce variant-specific antibodies during 
infection. Previously, we have shown that MSP2 is encoded on a polycistronic 
mRNA transcript in erythrocyte stages of A. marginale and defined 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 A. marginale infecting tick 
salivary glands. We also analyzed the variability of this genomic expression 
site in Oklahoma strain A. marginale transmitted from in vitro cultures to 
cattle and between cattle and ticks. The structure of the expression site and 
flanking regions was conserved except for sequence that encoded the MSP2 
hypervariable region. At least three different MSP2 variants were encoded in 
each A. marginale population. The major sequence 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 salivary glands most closely resembled those present 
in bovine blood at the time of acquisition of infection, whether infection was 
acquired from an acute or from a persistent rickettsemia. These variations in 
structure of an expression site for a major, immunoprotective outer membrane 
protein have important 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.