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Published on: March 8, 2012
Anaplasma marginale major surface protein 2 CD4+-T-cell epitopes are evenly distributed in conserved and
Jeffrey R Abbott1, Guy H Palmer, Chris J Howard
1Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, WA 99164, USA.
Abstract:
Organisms in the genus Anaplasma express an immunodominant major surface protein 2 (MSP2), composed of a central hypervariable region (HVR) flanked by highly conserved regions. Throughout Anaplasma marginale infection, recombination results in the sequential appearance of novel MSP2 variants and subsequent control of rickettsemia by the immune response, leading to persistent infection. To determine whether immune evasion and selection for variant organisms is associated with a predominant response against HVR epitopes, T-cell and linear B-cell epitopes were localized by measuring peripheral blood gamma interferon-secreting cells, proliferation, and antibody binding to 27 overlapping peptides spanning MSP2 in 16 cattle. Similar numbers of MSP2-specific CD4(+) T-cell epitopes eliciting responses of similar magnitude were found in conserved and hypervariable regions. T-cell epitope clusters recognized by the majority of animals were identified in the HVR (amino acids [aa] 171 to 229) and conserved regions (aa 101 to 170 and 272 to 361). In contrast, linear B-cell epitopes were concentrated in the HVR, residing within hydrophilic sequences. The pattern of recognition of epitope clusters by T cells and of HVR epitopes by B cells is consistent with the influence of protein structure on epitope recognition.
Insights
Anaplasma marginale uses major surface protein 2 (MSP2) variants for immune evasion. Both conserved and hypervariable regions of MSP2 contain T-cell epitopes, while B-cell epitopes are mainly in the hypervariable region.
Area of Science:
- Immunology
- Molecular Biology
- Veterinary Science
Background:
- Anaplasma marginale causes persistent infections in cattle through antigenic variation of its major surface protein 2 (MSP2).
- Recombination generates novel MSP2 variants, leading to immune evasion and chronic rickettsemia.
- Understanding epitope recognition is crucial for developing effective vaccines and control strategies.
Purpose of the Study:
- To investigate the distribution and recognition of T-cell and B-cell epitopes within the Anaplasma marginale MSP2.
- To determine if immune evasion is linked to specific epitope responses, particularly within the hypervariable region (HVR).
Main Methods:
- Localization of T-cell and linear B-cell epitopes by measuring gamma interferon secretion, proliferation, and antibody binding.
- Analysis of 27 overlapping peptides spanning the Anaplasma marginale MSP2 in 16 infected cattle.
- Characterization of epitope clusters in conserved and hypervariable regions of MSP2.
Main Results:
- Similar numbers of CD4+ T-cell epitopes were identified in both conserved and hypervariable regions of MSP2, with comparable response magnitudes.
- T-cell epitope clusters were found in both the HVR and conserved regions.
- Linear B-cell epitopes were predominantly located within the HVR, associated with hydrophilic sequences.
Conclusions:
- The immune response to Anaplasma marginale MSP2 involves T-cell epitopes in both conserved and variable regions.
- B-cell epitope concentration in the HVR suggests a role in immune evasion and host-pathogen interactions.
- Protein structure influences epitope recognition patterns by T and B cells, impacting Anaplasma marginale infection dynamics.
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