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Antigenic Variation (antigenic + variation)

Distribution by Scientific Domains

Life Sciences	73%
Medical Sciences	15%
3 Other Domains	12%

Selected Abstracts

Antigenic Variation in Ciliates: Antigen Structure, Function, Expression,

THE JOURNAL OF EUKARYOTIC MICROBIOLOGY, Issue 1 2007
MARTIN C. SIMON
ABSTRACT. In the past decades, the major focus of antigen variation research has been on parasitic protists. However, antigenic variation occurs also in free-living protists. The antigenic systems of the ciliates Paramecium and Tetrahymena have been studied for more than 100 yr. In spite of different life strategies and distant phylogenetic relationships of free-living ciliates and parasitic protists, their antigenic systems have features in common, such as the presence of repeated protein motifs and multigene families. The function of variable surface antigens in free-living ciliates is still unknown. Up to now no detailed monitoring of antigen expression in free-living ciliates in natural habitats has been performed. Unlike stochastic switching in parasites, antigen expression in ciliates can be directed, e.g. by temperature, which holds great advantages for research on the expression mechanism. Regulated expression of surface antigens occurs in an exclusive way and the responsible mechanism is complex, involving both transcriptional and post-transcriptional features. The involvement of homology-dependent effects has been proposed several times but has not been proved yet. [source]

Antigenic Variation in Pneumocystis,

THE JOURNAL OF EUKARYOTIC MICROBIOLOGY, Issue 1 2007
JAMES R. STRINGER
ABSTRACT. Pneumocystis is a genus containing many species of non-culturable fungi, each of which infects a different mammalian host. Pneumonia caused by Pneumocystis is a problem in immunodeficient humans, but not in normal humans. Nevertheless, it appears that Pneumocystis organisms cannot survive and proliferate outside of their mammalian hosts, suggesting that Pneumocystis parasitizes immunocompetent mammals. Residence in immunocompetent hosts may rely on camouflage perpetrated by antigenic variation. In P. carinii, which is found in rats, there exist three families of genes that appear to be designed to create antigenic variation. One gene family, which encodes the major surface glycoprotein (MSG), contains nearly 100 members. Expression of the MSG family is controlled by restricting transcription to the one gene that is linked to a unique expression site. Changes in the sequence of the MSG gene linked to the expression site occur and appear to be caused by recombination with MSG genes not at the expression site. Preliminary evidence suggests that gene conversion is the predominant recombination mechanism. [source]

Antigenicity and recombination of VlsE, the antigenic variation protein of Borrelia burgdorferi, in rabbits, a host putatively resistant to long-term infection with this spirochete

FEMS IMMUNOLOGY & MEDICAL MICROBIOLOGY, Issue 3 2007
Monica E. Embers
Abstract Borrelia burgdorferi, the Lyme disease pathogen, employs several immune-evasive strategies to survive in mammals. Unlike mice, major reservoir hosts for B. burgdorferi, rabbits are considered to be nonpermissive hosts for persistent infection. Antigenic variation of the VlsE molecule is a probable evasion strategy known to function in mice. The invariable region 6 (IR6) and carboxyl-terminal domain (Ct) of VlsE elicit dominant antibody responses that are not protective, perhaps to function as decoy epitopes that protect the spirochete. We sought to determine if either of these characteristics of VlsE differed in rabbit infection, contributing to its reputed nonpermissiveness. VlsE recombination was observed in rabbits that were given inoculations with either cultured or host-adapted spirochetes. Early observations showed a lack of anti-C6 (a peptide encompassing the IR6 region) response in most rabbits, so the anti-Ct and anti-C6 responses were monitored for 98 weeks. Anti-C6 antibody appeared as late as 20 weeks postinoculation, and the anti-Ct response, evident within the first 2 weeks, oscillated for prolonged periods of time. These observations, together with the recovery of cultivable spirochetes from tissue of one animal at 98 weeks postinoculation, challenge the notion that the rabbit cannot harbour a long-term B. burgdorferi infection. [source]

Antigenic variation with a twist , the Borrelia story

MOLECULAR MICROBIOLOGY, Issue 6 2006
Steven J. Norris
Summary A common mechanism of immune evasion in pathogenic bacteria and protozoa is antigenic variation, in which genetic or epigenetic changes result in rapid, sequential shifts in a surface-exposed antigen. In this issue of Molecular Microbiology, Dai et al. provide the most complete description to date of the vlp/vsp antigenic variation system of the relapsing fever spirochaete, Borrelia hermsii. This elaborate, plasmid-encoded system involves an expression site that can acquire either variable large protein (vlp) or variable small protein (vsp) surface lipoprotein genes from 59 different archival copies. The archival vlp and vsp genes are arranged in clusters on at least five different plasmids. Gene conversion occurs through recombination events at upstream homology sequences (UHS) found in each gene copy, and at downstream homology sequences (DHS) found periodically among the vlp/vsp archival genes. Previous studies have shown that antigenic variation in relapsing fever Borrelia not only permits the evasion of host antibody responses, but can also result in changes in neurotropism and other pathogenic properties. The vlsE antigenic variation locus of Lyme disease spirochaetes, although similar in sequence to the relapsing fever vlp genes, has evolved a completely different antigenic variation mechanism involving segmental recombination from a contiguous array of vls silent cassettes. These two systems thus appear to represent divergence from a common precursor followed by functional convergence to create two distinct antigenic variation processes. [source]

Fine antigenic variation within H5N1 influenza virus hemagglutinin's antigenic sites defined by yeast cell surface display

EUROPEAN JOURNAL OF IMMUNOLOGY, Issue 12 2009
Jian Li
Abstract Fifteen strains of mAb specific for HA of the A/Hong Kong/482/97 (H5N1) influenza virus were generated. The HA antigenic sites of the human A/Hong Kong/482/97 (H5N1) influenza virus were defined by using yeast cell surface-displaying system and anti-H5 HA mAb. Evolution analysis of H5 HA identified residues that exhibit diversifying selection in the antigenic sites and demonstrated surprising differences between residue variation of H5 HA and H3 HA. A conserved neutralizing epitope in the H5 HA protein recognized by mAb H5M9 was found using viruses isolated from 1997,2006. Seven single amino acid substitutions were introduced into the HA antigenic sites, respectively, and the alteration of antigenicity was assessed. The structure obtained by homology-modeling and molecular dynamic methods showed that a subtle substitution at residue 124 propagates throughout its nearby loop (152,159). We discuss how the structural changes caused by point mutation might explain the altered antigenicity of the HA protein. The results demonstrate the existence of immunodominant positions in the H5 HA protein, alteration of these residues might improve the immunogenicity of vaccine strains. [source]

PERSPECTIVE ARTICLE: Why do adaptive immune responses cross-react?

EVOLUTIONARY APPLICATIONS (ELECTRONIC), Issue 1 2009
Karen J. Fairlie-Clarke
Abstract Antigen specificity of adaptive immune responses is often in the host's best interests, but with important and as yet unpredictable exceptions. For example, antibodies that bind to multiple flaviviral or malarial species can provide hosts with simultaneous protection against many parasite genotypes. Vaccinology often aims to harness such imprecision, because cross-reactive antibodies might provide broad-spectrum protection in the face of antigenic variation by parasites. However, the causes of cross-reactivity among immune responses are not always known, and here, we explore potential proximate and evolutionary explanations for cross-reactivity. We particularly consider whether cross-reactivity is the result of constraints on the ability of the immune system to process information about the world of antigens, or whether an intermediate level of cross-reactivity may instead represent an evolutionary optimum. We conclude with a series of open questions for future interdisciplinary research, including the suggestion that the evolutionary ecology of information processing might benefit from close examination of immunological data. [source]

Detection and antigenic characterization of salmonid alphavirus isolates from sera obtained from farmed Atlantic salmon, Salmo salar L., and farmed rainbow trout, Oncorhynchus mykiss (Walbaum)

JOURNAL OF FISH DISEASES, Issue 3 2004
V A Jewhurst
Abstract A simple method of detecting the presence of the salmonid alphaviruses (SAVs), salmon pancreas disease virus (SPDV) and sleeping disease virus (SDV), from serum samples is described. Using a 96-well tissue-culture plate format, test sera are diluted in medium and added to chinook salmon embryo (CHSE-214) cells. After incubation for 3 days at 15 °C, plates are fixed and stained using a monoclonal antibody (mAb)-based immunoperoxidase (IPX) detection system, and virus-infected cells are observed microscopically by white light. Application of this screening test, which is now used routinely in our laboratory in conjunction with an IPX-based virus neutralization (IPX-VN) test for detecting antibodies to SAVs, has resulted in the recovery of 12 additional isolates from salmon sera and four additional isolates from trout sera. A low level of antigenic variation was detected when these SAV isolates were investigated by indirect immunofluorescence using a panel of mAbs raised to reference SPDV and SDV isolates. [source]

5, flanking region of var genes nucleate histone modification patterns linked to phenotypic inheritance of virulence traits in malaria parasites

MOLECULAR MICROBIOLOGY, Issue 6 2007
Jose Juan Lopez-Rubio
Summary In the human malaria parasite Plasmodium falciparum antigenic variation facilitates long-term chronic infection of the host. This is achieved by sequential expression of a single member of the 60-member var family. Here we show that the 5, flanking region nucleates epigenetic events strongly linked to the maintenance of mono-allelic var gene expression pattern during parasite proliferation. Tri- and dimethylation of histone H3 lysine 4 peak in the 5, upstream region of transcribed var and during the poised state (non-transcribed phase of var genes during the 48 h asexual life cycle), ,bookmarking' this member for re-activation at the onset of the next cycle. Histone H3 lysine 9 trimethylation acts as an antagonist to lysine 4 methylation to establish stably silent var gene states along the 5, flanking and coding region. Furthermore, we show that competition exists between H3K9 methylation and H3K9 acetylation in the 5, flanking region and that these marks contribute epigenetically to repressing or activating var gene expression. Our work points to a pivotal role of the histone methyl mark writing and reading machinery in the phenotypic inheritance of virulence traits in the malaria parasite. [source]

Alterations in local chromatin environment are involved in silencing and activation of subtelomeric var genes in Plasmodium falciparum

MOLECULAR MICROBIOLOGY, Issue 1 2007
Till S. Voss
Summary Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1), encoded by the var gene family, undergoes antigenic variation and plays an important role in chronic infection and severe malaria. Only a single var gene is transcribed per parasite, and epigenetic control mechanisms are fundamental in this strategy of mutually exclusive transcription. We show that subtelomeric upsB var gene promoters carried on episomes are silenced by default, and that promoter activation is sufficient to silence all other family members. However, they are active by default when placed downstream of a second active var promoter, underscoring the significance of local chromatin environment and nuclear compartmentalization in var promoter regulation. Native chromatin covering the SPE2 -repeat array in upsB promoters is resistant to nuclease digestion, and insertion of these regulatory elements into a heterologous promoter causes local alterations in nucleosomal organization and promoter repression. Our findings suggest a common logic underlying the transcriptional control of all var genes, and have important implications for our understanding of the epigenetic processes involved in the regulation of this major virulence gene family. [source]

Borrelia burgdorferi adhesins identified using in vivo phage display

MOLECULAR MICROBIOLOGY, Issue 1 2007
Styliani Antonara
Summary Borrelia burgdorferi, the agent of Lyme disease, disseminates from the site of deposition by Ixodes ticks to cause systemic infection. Dissemination occurs through the circulation and through tissue matrices, but the B. burgdorferi molecules that mediate interactions with the endothelium in vivo have not yet been identified. In vivo selection of filamentous phage expressing B. burgdorferi protein fragments on the phage surface identified several new candidate adhesins, and verified the activity of one adhesin that had been previously characterized in vitro. P66, a B. burgdorferi ligand for ,3 -chain integrins, OspC, a protein that is essential for the establishment of infection in mammals, and Vls, a protein that undergoes antigenic variation in the mammal, were all selected for binding to the murine endothelium in vivo. Additional B. burgdorferi proteins for which no functions have been identified, including all four members of the OspF family and BmpD, were identified as candidate adhesins. The use of in vivo phage display is one approach to the identification of adhesins in pathogenic bacteria that are not easily grown in the laboratory, or for which genetic manipulations are not straightforward. [source]

Antigenic variation with a twist , the Borrelia story

Host immunity modulates transcriptional changes in a multigene family (yir) of rodent malaria

MOLECULAR MICROBIOLOGY, Issue 3 2005
Deirdre A. Cunningham
Summary Variant antigens, encoded by multigene families, and expressed at the surface of erythrocytes infected with the human malaria parasite Plasmodium falciparum and the simian parasite Plasmodium knowlesi, are important in evasion of host immunity. The vir multigene family, encoding a very large number of variant antigens, has been identified in the human parasite Plasmodium vivax and homologues (yir) of this family exist in the rodent parasite Plasmodium yoelii. These genes are part of a superfamily (pir) which are found in Plasmodium species infecting rodents, monkeys and humans (P. yoelii, P. berghei, P. chabaudi, P. knowlesi and P. vivax). Here, we show that YIR proteins are expressed on the surface of erythrocytes infected with late-stage asexual parasites, and that host immunity modulates transcription of yir genes. The surface location and expression pattern of YIR is consistent with a role in antigenic variation. This provides a unique opportunity to study the regulation and expression of the pir superfamily, and its role in both protective immunity and antigenic variation, in an easily accessible animal model system. [source]

Iron availability regulates DNA recombination in Neisseria gonorrhoeae

MOLECULAR MICROBIOLOGY, Issue 5 2000
Carla D. Serkin
The pilus of Neisseria gonorrhoeae (the gonococcus Gc), the causative agent of gonorrhoea, promotes attachment of the gonococcus to the host epithelium and is essential for the establishment of disease. The ability of N. gonorrhoeae to infect previously exposed individuals is partially due to pilus antigenic variation. In addition, variation of the pilus has been proposed to function in the adaptation of the gonococcus to host environments. Previously, we described the development of a competitive reverse transcriptase (RT)-PCR assay that quantifies the frequency of pilin antigenic variation within a gonococcal population. Using this assay, the effect of different biologically relevant environmental conditions on the frequency of pilin antigenic variation was tested. Of the environmental conditions examined in vitro, only limited iron affected a significant change in the frequency of antigenic variation. Further investigation revealed that an observed increase in pilin antigenic variation reflected an increase in other DNA recombination and DNA repair processes within iron-starved cultures. In addition, this low iron-induced increase was determined to be independent of changes in RecA expression and was observed in a Fur mutant strain. As gonococci encounter conditions of low iron during infection, these data suggest that iron-limitation signals for increased recombinational events that are important for gonococcal pathogenesis. [source]

A novel mechanism for control of antigenic variation in the haemagglutinin gene family of Mycoplasma synoviae

MOLECULAR MICROBIOLOGY, Issue 4 2000
A. H. Noormohammadi
High-frequency phase and antigenic variation of homologous lipoprotein haemagglutinins has been seen in both the major avian mycoplasma pathogens, Mycoplasma synoviae and Mycoplasma gallisepticum. The expression and, hence, antigenic variation of the pMGA gene family (encoding these lipoproteins in M. gallisepticum) is controlled by variation in the length of a trinucleotide repeat motif 5, to the promoter of each gene. However, such a mechanism was not detected in preliminary observations on M. synoviae. Thus, the basis for control of variation in the vlhA gene family (which encodes the homologous haemagglutinin in M. synoviae) was investigated to enable comparison with its homologue in M. gallisepticum and with other lipoprotein gene families in mycoplasmas. The start point of transcription was identified 119 bp upstream of the initiation codon, but features associated with control of transcription in other mycoplasma lipoprotein genes were not seen. Comparison of three copies of vlhA revealed considerable sequence divergence at the 3, end of the gene, but conservation of the 5, end. Southern blot analysis of M. synoviae genomic DNA revealed that the promoter region and part of the conserved 5, coding sequence occurred as a single copy, whereas the remainder of the coding sequence occurred as multiple copies. A 9.7 kb fragment of the genome was found to contain eight tandemly repeated regions partially homologous to vlhA, all lacking the putative promoter region and the single-copy 5, end of vlhA, but extending over one of four distinct overlapping regions of the 3, coding sequence. Examination of sequential clones of M. synoviae established that unidirectional recombination occurs between the pseudogenes and the expressed vlhA, with duplication of pseudogene sequence and loss of the corresponding region previously seen in the expressed gene. Expression of the 5, end of two variants of the vlhA gene showed that they differed in their reaction with monoclonal antibodies specific for this region. These data suggest that the control of vlhA antigenic variation in M. synoviae is achieved by multiple gene conversion events using a repertoire of coding sequences to generate a chimeric expressed gene, with the greatest potential for variation generated in the region encoding the haemagglutinin. Thus, completely distinct mechanisms have been adopted to control antigenic variation in homologous gene families. [source]

Regulation of innate and acquired immunity in African trypanosomiasis

PARASITE IMMUNOLOGY, Issue 10-11 2005
J. M. MANSFIELD
SUMMARY African trypanosomes are well known for their ability to avoid immune elimination by switching the immunodominant variant surface glycoprotein (VSG) coat during infection. However, antigenic variation is only one of several means by which trypanosomes manipulate the immune system of their hosts. In this article, the role of parasite factors such as GPI anchor residues of the shed VSG molecule and the release of CpG DNA, in addition to host factors such as IFN-,, in regulating key aspects of innate and acquired immunity during infection is examined. The biological relevance of these immunoregulatory events is discussed in the context of host and parasite survival. [source]

Proteolytic cleavage of the Chlamydia pneumoniae major outer membrane protein in the absence of Pmp10

PROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 24 2007
Nicolai Juul
Abstract The genome of the obligate intracellular bacteria Chlamydia pneumoniae contains 21 genes encoding polymorphic membrane proteins (Pmp). While no function has yet been attributed to the Pmps, they may be involved in an antigenic variation of the Chlamydia surface. It has previously been demonstrated that Pmp10 is differentially expressed in the C. pneumoniae CWL029 isolate. To evaluate whether the absence of Pmp10 in the outer membrane causes further changes to the C. pneumoniae protein profile, we subcloned the CWL029 isolate and selected a clone with minimal Pmp10 expression. Subsequently, we compared the proteome of the CWL029 isolate with the proteome of the subcloned strain and identified a specific cleavage of the C-terminal part of the major outer membrane protein (MOMP), which occurred only in the absence of Pmp10. In contrast, when Pmp10 was expressed we predominantly observed full-length MOMP. No other proteins appeared to be regulated according to the presence or absence of Pmp10. These results suggest a close association between MOMP and Pmp10, where Pmp10 may protect the C-terminal part of MOMP from proteolytic cleavage. [source]

Antigenic Variation in Ciliates: Antigen Structure, Function, Expression,

Antigenic Variation in Pneumocystis,

,Nothing is permanent but change', , antigenic variation in persistent bacterial pathogens

CELLULAR MICROBIOLOGY, Issue 12 2009
Guy H. Palmer
Summary Pathogens persist in immunocompetent mammalian hosts using various strategies, including evasion of immune effectors by antigenic variation. Among highly antigenically variant bacteria, gene conversion is used to generate novel expressed variants from otherwise silent donor sequences. Recombination using oligonucleotide segments from multiple donors is a combinatorial mechanism that tremendously expands the variant repertoire, allowing thousands of variants to be generated from a relatively small donor pool. Three bacterial pathogens, each encoded by a small genome (< 1.2 Mb), illustrate this variant generating capacity and its role in persistent infection. Borrelia burgdorferi VlsE diversity is encoded and expressed on a linear plasmid required for persistence and recent experiments have demonstrated that VlsE recombination is necessary for persistence in the immunocompetent host. In contrast, both Treponema pallidum TprK and Anaplasma marginale Msp2 expression sites and donors are chromosomally encoded. Both T. pallidum and A. marginale generate antigenic variants in vivo in individual hosts and studies at the population level reveal marked strain diversity in the variant repertoire that may underlie pathogen strain structure and the capacity for re-infection and heterologous strain superinfection. Here, we review gene conversion in bacterial antigenic variation and discuss the short- and long-term selective pressures that shape the variant repertoire. [source]

Histones and histone modifications in protozoan parasites

CELLULAR MICROBIOLOGY, Issue 12 2006
William J. Sullivan Jr
Summary Protozoan parasites are early branching eukaryotes causing significant morbidity and mortality in humans and livestock. Single-celled parasites have evolved complex life cycles, which may involve multiple host organisms, and strategies to evade host immune responses. Consequently, two key aspects of virulence that underlie pathogenesis are parasite differentiation and antigenic variation, both of which require changes in the expressed genome. Complicating these requisite alterations in the parasite transcriptome is chromatin, which serves as a formidable barrier to DNA processes including transcription, repair, replication and recombination. Considerable progress has been made in the study of chromatin dynamics in other eukaryotes, and there is much to be gained in extending these analyses to protozoan parasites. Much of the work completed to date has focused on histone acetylation and methylation in the apicomplexans and trypanosomatids. As we describe in this review, such studies provide a unique vantage point of the evolutionary picture of eukaryotic cell development, and reveal unique phenomena that could be exploited pharmacologically to treat protozoal diseases. [source]

Myths, legends and realities of relapsing fever borreliosis

CLINICAL MICROBIOLOGY AND INFECTION, Issue 5 2009
S. J. Cutler
Relapsing fever borreliosis is often shrouded in mystery. From its discovery, it has evaded fulfilment of Koch's postulates. It has resulted in epidemic waves of infection, although it is now mostly localized to particular endemic pockets of infection. Structurally, this spirochaete breaks many paradigms for conventional microorganisms, e.g. through its segmented genomic structure. Disclosure of host,microbial interactions is revealing a plethora of mechanisms, from antigenic variation to binding of various host-derived proteins. We dispel some of the myths and explore current understanding of this much neglected area through a series of reviews within this theme section. [source]