Primary Structural Variation in Anaplasma marginale Msp2 Efficiently Generates Immune Escape Variants.
Infect Immun
; 83(11): 4178-84, 2015 Nov.
Article
em En
| MEDLINE
| ID: mdl-26259814
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 they 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 to 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. Biological 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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas da Membrana Bacteriana Externa
/
Variação Antigênica
/
Anaplasma marginale
/
Anaplasmose
/
Antígenos de Bactérias
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Infect Immun
Ano de publicação:
2015
Tipo de documento:
Article
País de afiliação:
Estados Unidos