Antigenic variation of parasite-derived antigens on the surface of Babesia bovis-infected erythrocytes

Abstract

The hemoparasite Babesia bovis antigenically alters the bovine erythrocyte membrane surface by expression of isolate-specific, parasite-derived polypeptides. To determine whether antigenic variation also occurred on the infected erythrocyte surface, a calf was infected once with parasitized erythrocytes carrying the C9.1 clonal line of B. bovis. In vitro cultures then were established periodically from the peripheral blood and analyzed with sequentially collected sera from the same animal. The surface reactivity of infected erythrocytes cultured from the infected animal varied over time, on the basis of reactivity in live cell immunofluorescence, surface immunoprecipitation, and panning assays. Subclones C8 and H10, established from day 41 cultures, were analyzed immunochemically. A loss of immunoreactivity was observed in antigens corresponding to the 113and 128-kDa parasite-derived antigens of clone C9.1, demonstrating epitopic variation in these antigens; the immunochemical recognition of these antigens paralleled the results of live cell immunofluorescence and panning assays. Concomitant size polymorphism suggested polypeptide structural variation of these antigens as well. Calves infected by inoculation of infected blood or by injection of cloned parasites from in vitro cultures rapidly developed antibodies which cross-reacted among the clonal variant lines, suggesting the presence of common as well as unique epitopes. These results demonstrate that antigenic variation occurs on the surface of B. bovis-infected erythrocytes and that the parasite-derived antigens of 113 and 128 kDa compose at least a part of the antigens undergoing variation.

Twenty‐Fold Difference in Evolutionary Rates between the Mitochondrial and Plastid Genomes of Species with Secondary Red Plastids

“…We were also able to glean interstrain organelle sequence data from the apicomplexan parasite B. bovis (Alveolata), which also has a secondary, red algal-derived plastid (Fichera and Roos 1997;Janousˇkovec et al 2010), but in this case is an especially interesting comparison because the plastid is nonphotosynthetic and its genome is regarded as rapidly evolving. Complete mtDNA and ptDNA sequences from the B. bovis C9.1 clonal line (Allred et al 1994), which originates from the "Mexico" isolate (Hines et al 1989), were compared with those of the unrelated "Texas" T2Bo isolate (Goff, Johnson, and Cluff 1998). Surprisingly, not a single polymorphism was found in the ptDNA, which is~35-kb long and has~15 kb of silent sites, whereas for the mtDNA, which is 6-kb long with~3 kb of silent sites, the overall level of genetic divergence was 1.2 9 10 À3 , with average synonymousand amino-acid-replacement-site divergences of 5.5 9 10 À3 and 0.8 9 10 À3 , respectively (Table 1).…”

Cytoadherence of Babesia bovis -Infected Erythrocytes to Bovine Brain Capillary Endothelial Cells Provides an In Vitro Model for Sequestration

“…Infection with the intraerythrocyte protozoal parasite Babesia bovis stimulates an immune response that controls but fails to eradicate the parasite, resulting in long-term, chronic infections (7,13,29). One mechanism that enables the parasite to hide from the host immune defenses is the ability of infected erythrocytes (IRBCs) carrying mature parasites to become sequestered in the capillaries (15,47,49), presumably avoiding splenic clearance (4).…”

“…Each parasite induces the formation of knobby protrusions on the surface of the IRBC (3,8,27,47), which mediate adhesion to the endothelium (2,27,45,47,49). Parasite-derived antigens associated with the IRBC surface, and potentially with cytoadhesion, are subject to rapid antigenic variation (7,12). Both parasites are sequestered in the capillaries of many host tissues, an activity thought to contribute significantly to the pathologic effects of both malaria and babesiosis (1,15,28,37,38,(47)(48)(49), particularly the cerebral complications that are the hallmark of these two diseases (1,2,15,28,47).…”

C3 contributes to the cross‐protective immunity induced by Babesia gibsoni phosphoriboprotein P0 against a lethal B. rodhaini infection

“…CD4+ T cells respond to exogenously presented antigens and enhance the high‐affinity of immunoglobulin isotype production, which is able to label the parasites and interfere in the entry to the cells (8). The parasites reside in erythrocytes that are devoid of major histocompatibility complex molecules, but variant erythrocyte surface antigen 1 isolated from the surface of parasitized erythrocytes might be a target for the host antibody (9,10). The opsonizing antibodies make the parasitized erythrocytes more recognizable and vulnerable to phagocytosis (11–13).…”