Disease relevance of Antigenic Variation

• Differential immunoscreening and RT-PCR demonstrate that IFN-gamma-mediated signals facilitate spirochete recombination at the variable major protein like sequence locus, a site for early antigenic variation in vivo, and that recombination rates by B. burgdorferi N40 are lower in IFN-gammaR-deficient mice than in control animals [1].
• The antigenic diversity threshold theory predicts that antigenic sites of human immunodeficiency virus type 1, such as the V3 region of the external glycoprotein gp120, evolve more rapidly during the symptom-free period in individuals progressing to AIDS than in those who remain asymptomatic for a long time [2].
• To define the structure of the caprine arthritis-encephalitis virus (CAEV) env gene and characterize genetic changes which occur during antigenic variation, we sequenced the env genes of CAEV-63 and CAEV-Co, two antigenic variants of CAEV defined by serum neutralization [3].
• Anaplasma phagocytophilum immunodominant polymorphic major surface protein P44s have been hypothesized to go through antigenic variation, but the within-host dynamics of p44 expression has not been demonstrated [4].
• The antigenic variation of the relapsing fever agent Borrelia hermsii is associated with changes in the expression of the Vlp and Vsp outer membrane lipoproteins [5].

High impact information on Antigenic Variation

• The malaria parasite Plasmodium falciparum undergoes antigenic variation to evade host immune responses through switching expression of variant surface proteins encoded by the var gene family [6].
• F2 more prominently lines the channels and makes the majority of the glycan contacts, underscoring its role in cytoadherence and in antigenic variation in malaria [7].
• In P. falciparum, subtelomeric domains are conserved and contain ordered arrays of members of multigene families, such as var, rif and stevor, encoding virulence determinants of cytoadhesion and antigenic variation [8].
• Telomeric reciprocal recombination as a possible mechanism for antigenic variation in trypanosomes [9].
• Recently, however, IFN-alpha has been found to include at least eight different subtypes, as indicated by measurement of antigenic variability, DNA hybridization and amino acid sequencing [10].

Chemical compound and disease context of Antigenic Variation

• To determine the antigenic diversity of P pili, we purified the pili from 14 bacteremic E. coli strains which caused mannose-resistant hemagglutination [11].
• Variance in fibronectin binding and fnb locus polymorphisms in Staphylococcus aureus: identification of antigenic variation in a fibronectin binding protein adhesin of the epidemic CMRSA-1 strain of methicillin-resistant S. aureus [12].
• To recognize the antigenic diversity of the lipopolysaccharide (LPS) responsible for this classification, the Dresden Legionella LPS MAb panel, containing 98 monoclonal antibodies (MAbs), was created [13].
• The C6 enzyme-linked immunosorbent assay (ELISA), based on a peptide (C6) that reproduces the sequence of invariable region 6 of VlsE, the antigenic variation protein of Borrelia burgdorferi, has been shown to be a sensitive and specific test for the serologic diagnosis of Lyme disease [14].
• Multiple inverted DNA repeats of Bacteroides fragilis that control polysaccharide antigenic variation are similar to the hin region inverted repeats of Salmonella typhimurium [15].

Biological context of Antigenic Variation

• P. falciparum parasites generate high levels of variability in gene families that comprise virulence determinants of cytoadherence and antigenic variation, such as the var genes [16].
• As all three species exhibit antigenic variation, small chromosomes with telomeric variant surface glycoprotein genes cannot be vital to the mechanism of antigenic variation [17].
• The PfEMP1 protein, which is encoded by the large var gene family, shows antigenic variation and changes in binding phenotype associated with alterations in antigenicity [18].
• Antigenic variation in the bloodstream results either from DNA rearrangements or from a change in telomeric chromatin structure, and stage-specific regulation of antigen synthesis is linked to differential control of RNA elongation, processing, stability, and/or translation [19].
• The genome contains unusual functional pseudogenes that belong to the msp2 superfamily and play an integral role in surface coat antigenic variation, and are thus distinctly different from pseudogenes described as byproducts of reductive evolution in other Rickettsiales [20].

Anatomical context of Antigenic Variation

• This finding that a mutation at amino acid 585 on gp41 results in nonrecognition by human leukocyte antigen A24-restricted CD8+ cytotoxic T lymphocytes suggests that antigenic variation at T-cell epitopes contributes to the failure of immune control of human immunodeficiency virus type 1 infections [21].
• Intraerythrocytic Plasmodium falciparum parasites at the trophozoite and schizont stages synthesize a greater than 200-kDa protein, the mature erythrocyte surface antigen (MESA), that is localized at the membrane of infected red blood cells and manifests size polymorphism and antigenic diversity among parasite isolates [22].
• Cyclophosphamide may delete suppressor lymphocytes allowing enhanced production of antibodies which may not only protect, but induce antigenic variation [23].
• Although IgTCR-modified T cells function well in vitro, therapeutic applications in humans may be complicated by various factors, such as the availability of appropriate T-cell cytokines, high systemic levels of antagonistic soluble CEA, and antigenic diversity in tumor cell populations [24].
• These results suggest that PLC/PRF/5 may be a suitable continuous cell line, and an alternative to monkey kidney cells, for the isolation and monitoring of antigenic variation of influenza viruses [25].

Associations of Antigenic Variation with chemical compounds

• The WB isolate of Giardia lamblia expresses a cysteine-rich 170-kD surface antigen (CRP170) that undergoes antigenic variation [26].
• Although there is little genetic relatedness between and large antigenic diversity between and among the two chlamydial species, one antigenic determinant has been preserved among all serovars: the genus-specific lipopolysaccharide epitope [27].
• Here we describe the development of a de novo C4 hybrid protein with allotypic and antigenic diversity resulting from nonhomologous intra or interchromosomal recombination of the maternal chromosomes [28].
• A serine-versus-leucine difference is responsible for the antigenic variation [29].
• Antigenic variation was demonstrated with monoclonal antibodies raised against FMDV C3 [30].

Gene context of Antigenic Variation

• The observed pattern of DNA variation in this region is consistent with the selection model developed in this article, suggesting that strong selection might be working to maintain the RHCE/RHD antigen variation in the two-locus system [31].
• A homologue of the recombination-dependent growth gene, rdgC, is involved in gonococcal pilin antigenic variation [32].
• Because of the antigenic variation in the serum CEA, markedly different CEA concentrations (varying by three orders of magnitude) were measurable by two different antisera (Roche and Montreal) [33].
• The outer membrane proteins (OMPs) P1 and P2 of Haemophilus influenzae type b exhibit molecular size and antigenic variation [34].
• Analysis of antigenic diversity of MSP5 shows a lack of sequence variation between various isolates of P. falciparum from different geographical locations, a feature unusual for surface proteins of merozoites and one that may simplify vaccine formulation [35].

Analytical, diagnostic and therapeutic context of Antigenic Variation

• Virus neutralization tests performed with sera from experimentally infected salmon indicated that SPDV and SDV belonged to the same serotype; however, antigenic variation was detected among SDV and geographically different SPDV isolates by using monoclonal antibodies [36].
• The parasites have the ability to escape immune control by two means: by antigenic variation of the surface glycoprotein coat so that waves of variant parasites arise and by inducing a general immunosuppression affecting immune responses to the parasite as well as to parasite-unrelated antigens [37].
• Assignment of the gene(s) involved in expression of the Meth A antigen to the distal region of chromosome 12, the same region encoding Igh, raised the possibility that genetic elements responsible for antibody idiotype could be involved in the antigenic diversity of tumour-specific transplantation antigens [38].
• Eighteen Coxiella burnetii strains from a variety of clinical and geographical sources were screened for antigenic variation of polypeptides by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) coupled with Coomassie brilliant blue (CBB) staining or immunoblotting [39].
• Results illustrate a continued antigenic variation in an endemic area where vaccination has been used; however, asymmetric serological reactions between the A24 vaccine strain and the most recent field isolate indicated that a vaccine incorporating A24 should still give adequate protection [40].

References