Journal article
Maintenance of Antibody to Pathogen Epitopes Generated by Segmental Gene Conversion Is Highly Dynamic during Long-Term Persistent Infection
Infection and immunity, Vol.75(11), pp.5185-5190
11/2007
Handle:
https://hdl.handle.net/2376/112753
PMCID: PMC2168278
PMID: 17785476
Abstract
Multiple bacterial and protozoal pathogens utilize gene conversion to generate rapid intrahost antigenic variation. Both large- and small-genome pathogens expand the size of the variant pool via a combinatorial process in which oligonucleotide segments from distinct donor loci are recombined in various combinations into expression sites. Although the potential combinatorial diversity generated by this segmental gene conversion mechanism is quite large, the functional variant pool depends on whether immune responses against the recombined segments are generated and maintained, regardless of their specific combinatorial context. This question was addressed by tracking the
Anaplasma marginale
variant population and corresponding segment-specific immunoglobulin G (IgG) antibody responses during long-term infection. Antibody was induced early in
A. marginale
infection, predominately against the surface-exposed hypervariable region (HVR) rather than against the invariant conserved flanking domains, and these HVR oligopeptides were most immunogenic at the time of acute bacteremia, when the variant population is derived via recombination from a single donor locus. However antibody to HVR oligopeptides was not consistently maintained during persistent infection, despite reexpression of the same segment, although in a different combinatorial context. This dynamic antibody recognition over time was not attributable to the major histocompatibility complex haplotype of individual animals or use of specific
msp2
donor alleles. In contrast, the position and context of an individual oligopeptide segment within the HVR were significant determinants of antibody recognition. The results unify the genetic potential of segmental gene conversion with escape from antibody recognition and identify immunological effects of variant mosaic structure.
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Details
- Title
- Maintenance of Antibody to Pathogen Epitopes Generated by Segmental Gene Conversion Is Highly Dynamic during Long-Term Persistent Infection
- Creators
- Yan Zhuang - Programs in Vector-Borne Diseases and Immunology, Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, WashingtonJames E Futse - Programs in Vector-Borne Diseases and Immunology, Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, WashingtonWendy C Brown - Programs in Vector-Borne Diseases and Immunology, Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, WashingtonKelly A Brayton - Programs in Vector-Borne Diseases and Immunology, Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, WashingtonGuy H Palmer - Programs in Vector-Borne Diseases and Immunology, Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, Washington
- Publication Details
- Infection and immunity, Vol.75(11), pp.5185-5190
- Academic Unit
- Veterinary Microbiology and Pathology, Department of; Paul G. Allen School for Global Animal Health
- Publisher
- American Society for Microbiology (ASM)
- Identifiers
- 99900548021101842
- Language
- English
- Resource Type
- Journal article