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Rights Statements InC/1.0 , Open Access
Accepted manuscript
Primary structural variation in Anaplasma marginale Msp2 efficiently generates immune escape variants
Infection and immunity : IAI., Vol.83(11), pp.4178-4184
11/2015
Handle:
https://hdl.handle.net/2376/6004
Abstract
Antigenic variation allows microbial pathogens to evade immune clearance and establish persistent infection. Anaplasma marginale utilizes gene conversion of a repertoire of silent msp2 alleles into a single active expression site to encode unique Msp2 variants. As the genomic complement of msp2 alleles alone is insufficient to generate the number of variants required for persistence, A. marginale uses segmental gene conversion, in which oligonucleotide segments from multiple alleles are recombined into the expression site to generate a novel msp2 mosaic, not represented elsewhere in the genome. Whether these segmental changes are sufficient to evade a broad antibody response is unknown. We addressed this question by identifying Msp2 variants that differed in primary structure within the immunogenic hypervariable region microdomains and tested whether these represented true antigenic variants. The minimal primary structural difference between variants was a single amino acid resulting from a codon insertion and overall the amino acid identity among paired microdomains ranged from 18-92%. Collectively, 89% of the expressed structural variants were also antigenic variants across all biological replicates, independent of a specific host major histocompatibility complex haplotype. Biologic relevance is supported by the following: i) all structural variants were expressed during infection of a natural host; ii) the structural variation observed in the microdomains corresponded to the mean length of variants generated by segmental gene conversion; and iii) antigenic variants were identified using a broad antibody response that developed during infection of a natural host. The findings demonstrate that segmental gene conversion efficiently generates Msp2 antigenic variants.
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Details
- Title
- Primary structural variation in Anaplasma marginale Msp2 efficiently generates immune escape variants
- Creators
- Telmo Graca (Author)Lydia Paradiso (Author)Shira L. Broschat (Author)Susan M. Noh (Author)Guy H. Palmer (Author)
- Publication Details
- Infection and immunity : IAI., Vol.83(11), pp.4178-4184
- Academic Unit
- Paul G. Allen School for Global Animal Health; Electrical Engineering and Computer Science, School of; Veterinary Microbiology and Pathology, Department of
- Identifiers
- 99900501005501842
- Copyright
- In copyright ; openAccess ; http://rightsstatements.org/vocab/InC/1.0/ ; http://purl.org/eprint/accessRights/OpenAccess
- Language
- English
- Resource Type
- Accepted manuscript