Anaplasma marginale Major Surface Protein 2 CD4 ⁺ -T-Cell Epitopes Are Evenly Distributed in Conserved and Hypervariable Regions (HVR), Whereas Linear B-Cell Epitopes Are Predominantly Located in the HVR

Abstract

Organisms in the genus

Identification ofAnaplasma marginaleOuter Membrane Protein Antigens Conserved betweenA. marginaleSensu Stricto Strains and the LiveA. marginalesubsp.centraleVaccine

“…Interestingly, while the amino acid sequence of the C-terminal region is more conserved between the vaccine strain and the challenge St. Maries strain than is the N-terminal region sequence, the primary cross-reactivity was to the N terminus. This preferential reactivity of the N terminus over the C terminus is not specific to live immunization nor to the immunoblot assay, as enzymelinked immunosorbent assay (ELISA) mapping following outer membrane immunization yielded the same conclusion (1,44). While Msp3 was not similarly mapped, the shared gene locus structure, HVR recombination mechanism, and pattern of conserved N-and C-terminal regions with a central, surfaceexposed HVR domain supports that lessons learned from Msp2 are applicable to Msp3 (7,9,18,26).…”

“…Finally, although vaccine-induced IgG2 against the challenge strain Msp2 HVRs was not required at the time of challenge, a role for the Msp2 conserved regions in priming the immune response cannot be ruled out. The N-and C-terminal regions, while not surface exposed, contain CD4 ϩ T lymphocyte epitopes conserved between the vaccine strain and sensu stricto strains, including the St. Maries strain (1,8,38). These epitopes prime helper T cells which may enhance de novo antibody production against the heterologous HVR upon challenge (34).…”

Expansion of Variant Diversity Associated with a High Prevalence of Pathogen Strain Superinfection under Conditions of Natural Transmission

“…The N-and C-terminal regions, which form ␤ barrels, are highly conserved among all variants, and the encoding 5= and 3= domains provide the "anchor" points for gene conversion (8,17). Although conserved, these N-and C-terminal regions are poorly immunogenic and only very weakly bound by antibody from either natural infection or in immunized and protected animals (1,3,43). In contrast, the hydrophilic central region is surface exposed and highly immunogenic but also highly variable among donor alleles within a strain and alleles across strains (1, 3, 16, 34, 43).…”

Two Monoclonal Antibodies with Defined Epitopes of P44 Major Surface Proteins NeutralizeAnaplasma phagocytophilumby Distinct Mechanisms

“…B-cell epitopes are present predominantly in the central hypervariable region, and only a few B-cell epitopes are present in the N-terminal conserved region of Msp2 of the A. marginale Florida strain (1). The native MSP2 protein isolated from A. marginale was reported to block hemagglutination of bovine erythrocytes with A. marginale in vitro (23).…”