Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Antigenic Variation”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 163 records · Page 9Linked to original sources
PubMed1997

Shared themes of antigenic variation and virulence in bacterial, protozoal, and fungal infections.

Pathogenic microbes have evolved highly sophisticated mechanisms for colonizing host tissues and evading or deflecting assault by the immune response. The ability of these microbes to avoid clearance prolongs infection, thereby promoting their long-term survival within individual hosts and, through transmission, between hosts. Many pathogens are capable of extensive antigenic changes in the face of the multiple constitutive and dynamic components of host immune defenses. As a result, highly diverse populations that have widely different virulence properties can arise from a single infecting organism (clone). In this review, we consider the molecular and genetic features of antigenic variation and corresponding host-parasite interactions of different pathogenic bacterial, fungal, and protozoan microorganisms. The host and microbial molecules involved in these interactions often determine the adhesive, invasive, and antigenic properties of the infecting organisms and can dramatically affect the virulence and pathobiology of individual infections. Pathogens capable of such antigenic variation exhibit mechanisms of rapid mutability in confined chromosomal regions containing specialized genes designated contingency genes. The mechanisms of hypermutability of contingency genes are common to a variety of bacterial and eukaryotic pathogens and include promoter alterations, reading-frame shifts, gene conversion events, genomic rearrangements, and point mutations.

Animals↗
PubMed1999

Human antibody responses to VlsE antigenic variation protein of Borrelia burgdorferi.

VlsE is a 35-kDa surface-exposed lipoprotein of Borrelia burgdorferi that was shown previously to undergo antigenic variation through segmental recombination of silent vls cassettes with vlsE during experimental mouse infections. Previous data had indicated that sera from North American Lyme disease patients and experimentally infected animals contained antibodies reactive with VlsE. In this study, sera from patients with Lyme disease, syphilis, and autoimmune conditions as well as from healthy controls were examined for reactivity with VlsE by Western blotting and enzyme-linked immunosorbent assay (ELISA). Strong Western blot reactivity to a recombinant VlsE cassette region protein was obtained consistently with Lyme disease sera. Although sera from Lyme disease patients also reacted with a band corresponding to VlsE in B. burgdorferi B31-5A3, interpretation was complicated by low levels of VlsE expression in in vitro-cultured B. burgdorferi and by the presence of comigrating bands. An ELISA using recombinant VlsE was compared with an ELISA using sonically disrupted B. burgdorferi as the antigen. For a total of 93 Lyme disease patient sera examined, the VlsE ELISA yielded sensitivities of 63% for culture-confirmed erythema migrans cases and 92% for later stages, as compared to 61 and 98%, respectively, for the "whole-cell" ELISA. The specificities of the two assays with healthy blood donor sera were comparable, but the VlsE ELISA was 90% specific with sera from syphilis patients, compared to 20% specificity for the whole-cell ELISA with this group. Neither assay showed reactivity with a panel of sera from 20 non-Lyme disease arthritis patients or 20 systemic lupus erythematosus patients. Our results indicate that VlsE may be useful in the immunodiagnosis of Lyme disease and may offer greater specificity than ELISAs using whole B. burgdorferi as the antigen.

Antibodies, Bacterial↗
PubMed1988

Antigenic variation among 173 strains of type 3 poliovirus isolated in Finland during the 1984 to 1985 outbreak.

Antigenic properties of 128 clinical type 3 poliovirus isolates of the 1984 to 1985 Finland outbreak from 95 persons and 45 strains from sewage water specimens were evaluated using five neutralizing monoclonal antibodies (MAbs) directed against an antigenic site (designated site 1) on VP1 at amino acids 89 to 100. All five MAbs neutralized the type 3 poliovirus strains used in the vaccines, P3/Saukett and P3/Sabin, but none of them neutralized the prototype strain of the outbreak (P3/Finland/23127/84). Forty-six percent of the clinical isolates resembled the prototype strain (class A) while the rest of the isolates were neutralized by one or more of the MAbs (classes B to D). Although an antigenic drift from A to one of the other classes was observed in sequential specimens from several individuals, no clear-cut overall change in the class distribution was found within the 3 months time span of the outbreak. Homogeneous virus populations were isolated from the sewage specimens using a microtitre endpoint dilution method. The last positive sewage specimens which were obtained in January to February 1985 still had a majority of the class A strain. Some of the clinical isolates were also tested using MAbs directed against distinct antigenic sites. These studies showed that strains that gave the same pattern of reactivity with site 1 MAbs could be differentiated using antibodies directed against other sites. Fifteen strains belonging to different antigenic subclasses were subjected to partial RNA sequencing of the genome region coding for antigenic site 1. The antigenic variation was usually, but not always associated with corresponding amino acid substitutions in antigenic site 1. These results indicate that the antigenic sites of type 3 poliovirus vary extensively within a given outbreak and even during replication in a given host. This variation may have both pathogenetic and epidemiological significance.

Amino Acid Sequence↗
PubMed2005

Trypanosoma brucei DMC1 does not act in DNA recombination, repair or antigenic variation in bloodstream stage cells.

Homologous recombination acts in the repair of cellular DNA damage and can generate genetic variation. Some of this variation provides a discrete purpose in the cell, although it can also be genome-wide and contribute to longer-term natural selection. In Trypanosoma brucei, a eukaryotic parasite responsible for sleeping sickness disease in sub-Saharan Africa, homologous recombination acts to catalyse antigenic variation, an immune evasion strategy involving switches in variant surface glycoprotein. In addition, T. brucei can undergo genetic exchange by homologous recombination in the tsetse vector, and some evidence suggests that this occurs by meiosis. Here, we show that T. brucei, Trypanosoma cruzi and Leishmania major each contain a single copy gene whose product is highly related to the eukaryotic meiosis-specific protein Dmc1, which is structurally and functionally related to Rad51. We show that T. brucei DMC1 is transcribed in the bloodstream stage of the parasite, where the gene can be mutated by reverse genetic disruption. DMC1 mutation does not, however, result in detectable alterations in DNA repair, recombination or antigenic variation efficiency in this life cycle stage.

Amino Acid Sequence↗
PubMed1975

Bovine veneral vibriosis: antigenic variation of the bacterium during infection.

Host parasite relationships in the female genital tract were studied in bovine venereal vibriosis by investigating agglutinin production and alterations in superficial antigens of the bacterium during the course of infection in two heifers. Cervicovaginal mucus (CVM) steamed cell agglutinins were shown to appear earlier and remain at consistently higher levels than whole-cell agglutinins. Whole-cell agglutinin titers fluctuated much more than steamed cell titers, suggesting possible changes in whole-cell antigens. Marked antigenic variation was demonstrated in successive monthly CVM isolates from the two heifers by agglutination tests with rabbit antisera of various specificities. Some changes in CVM antibody specificity during the infection were noted also. Antigenic variation in the bacterium was proposed as a mechanism for maintenance of the asymptomatic cervicovaginal carrier state in the presence of antibody.

Agglutination Tests↗
PubMed1982

Antigenic variation in cancer metastasis: immune escape versus immune control.

Antigenic variation in cancer metastasis was observed in a syngeneic murine tumor system consisting of a low metastatic parental tumor line (derived from a methylcholanthrene-induced DBA/2 T lymphoma, Eb), a high metastatic spontaneous variant thereof (ESb), and a low metastatic 'revertant' from ESb (ESb-M). All three lines expressed tumor-associated transplantation antigens (TATA) which elicited specific T cell-mediated antitumor immune reactions in the host. The strongest host response was elicited upon intradermal inoculation. It could be followed by (a) the infiltration of the locally growing tumor by host cells, such as lymphocytes and macrophages, (b) the establishment of specific systemic antitumor immunity, (c) the generation of immune cells capable of transferring protective antitumor immunity into a normal syngeneic recipient, and (d) the generation of tumor specific cytotoxic T lymphocytes (CTL). Anti-TATA CTL were used as typing reagents to investigate the stability or variability in the TATA expression by cloned tumor cell lines. Antigenic variability in the TATA expression was seen under various conditions: (a) clone-dependent variation in the sensitivity to anti-TATA CTL lysis upon prolonged growth in tissue culture, (b) qualitative change in the TATA (TATA1 leads to TATA2) upon successive i.p. transplantation of the parental Eb tumor line and, (c) generation of TATA negative immune escape variants (TATA2 leads to TATA-) during metastasis formation from a s.c. site. The relative inefficiency of specific immunization procedures against ESb was found to be due to the effective generation of TATA negative variants by this highly metastatic tumor. The balance between immune control and immune escape could be influenced to the advantage of the host by some means, for instance optimizing the route of antitumor-immune sensitization or by infusion of allogeneic but H-2 identical antitumor-immune T cells. Such immune cells recognized the tumor via minor histocompatibility antigens and thus circumvented the need of TATA recognition. Finally, manipulations at the cell surface of the highly malignant ESb tumor such as those introduced in the ESb-M variant were found to dramatically effect its metastatic potential.

Animals↗
PubMed1995

[Antigenic variation and the problem of vaccines against African trypanosomes].

African trypanosomes evade the immune response of their host through continuous changes of their major surface antigen, the VSG. This antigenic variation is achieved by either alternative activation of different expression sites for the VSG gene, or DNA rearrangements occurring within a given site. Several minor but invariant surface proteins have recently been characterized. This is especially the case for some surface receptors, which appear to be located in an invagination of the plasma membrane termed the flagellar pocket. These proteins may represent useful targets for new vaccination strategies.

Animals↗
PubMed1993

Differential protein expression and surface presentation generate high-frequency antigenic variation in Mycoplasma fermentans.

Mycoplasma fermentans, a wall-less prokaryote, is currently under investigation as a potential human pathogen. Recently, several surface lipoproteins have been shown to vary in expression between M. fermentans strains. Using specific antibodies to these lipoproteins, we investigated the extent and nature of antigenic variation within this species. Immunoscreening of type strain PG18 agar-grown colonies revealed marked heterogeneity in expression of distinct surface lipoproteins. Subsequent isolation and propagation of clonal isolates established isogenic lineages which displayed high-frequency (10(-2) to 10(-5) per generation) antigenic phase variation. [35S]cysteine-labeled protein profiles and Western immunoblots of phase-variant clones showed that several distinct integral membrane proteins undergo noncoordinate variation in expression. In addition to differential expression of epitope-bearing lipoproteins, differential accessibility of epitopes to antibodies was also documented as a mechanism generating surface phenotypic variation. Examination of one strain-variant antigen showed high-frequency phase variation to underlie previously observed antigenic differences between strains of this species. Thus, M. fermentans has a complex system capable of creating rapid changes in surface mosaics. This may profoundly affect mycoplasma-host interactions and may limit the methods by which populations of M. fermentans may be studied in vivo.

Antibodies, Monoclonal↗
PubMed1990

The use of immunogold-silver staining to study antigen variation and bacterial entry into eukaryotic cells by conventional light microscopy.

Immunogold-silver staining is a sensitive staining technique that enables the visualisation of the presence of individual antigens by conventional light microscopy. The application of this method to detect the antigenic heterogeneity of bacterial surface components and also the localisation of intracellular or extracellular bacteria is described. The latter application involved selective immuno-silver staining of the extracellular bacteria and counterstaining of the intracellular bacteria and the eukaryotic cells by crystal violet. The efficacy of the assay was confirmed by transmission electronmicroscopy of the silver-stained specimens. Immunogold-silver staining was shown to be useful for studying bacterial antigen variation and the uptake of bacteria by eukaryotic cells.

Antigenic Variation↗
PubMed1999

Antigenic variation in Plasmodium falciparum: mechanisms and consequences.

In the past year, the major advances in malaria antigenic variation have been concerned with the transcription and switching of variant antigen genes, and the functional expression of regions of the major variant antigen. Also, new variant gene families have been discovered as a result of the Malaria Genome Project.

Animals↗
PubMed1992

Antigenic variation of Mycoplasma gallisepticum, as detected by use of monoclonal antibodies.

A panel of monoclonal antibodies (MAb) developed against Mycoplasma gallisepticum strain PG31 was used to probe the antigenic profiles of 5 recognized strains (PG31, R, S6, F, A5969) and 6 field isolates of M gallisepticum. Monoclonal antibody G9 predominantly recognized antigens at apparent molecular mass positions of 90 to 98 kDA. The MAb reacted with all strains and isolates, but the molecular mass position of the antigens varied among some mycoplasmas. Monoclonal antibody G12 reacted with all strains and isolates of M gallisepticum and had an identical banding pattern. However, MAb G10 and G11 reacted selectively only with a limited number of strains and/or isolates. Surface distribution of the MAb-recognized antigens was revealed by immunoelectron microscopy. Partial physicochemical characterization of MAb G9-recognized antigens identified glycopeptide characteristics. Monoclonal antibody G9 reacted with surface antigens and, hence, participated in agglutination of M gallisepticum. However, the degree of agglutination varied among the various strains and isolates, indicating a quantitative or conformational limitation or an alteration in the anomeric expression of the epitopes. Antigenic variation in M gallisepticum may be mediated by immunologic selective pressures, or a proclivity for habit niche in the host.

Agglutination Tests↗
PubMed2002

Antigenic variation of Ehrlichia chaffeensis resulting from differential expression of the 28-kilodalton protein gene family.

The transcriptional activity and allele variation of the 28-kDa outer membrane protein gene (p28) of Ehrlichia chaffeensis were analyzed to determine the mechanism of the antigenic variation of the 28-kDa outer membrane proteins. Reverse transcriptase PCR amplification of mRNA indicated that 16 of the 22 members of the p28 multigene family were transcribed. Amino acid sequence analysis indicated that the p28-19 protein was produced in vitro in the Arkansas strain. The p28-19 gene and its promoter region were sequenced and compared in 12 clinical isolates of E. chaffeensis to determine allele variation. The variation of the p28-19 gene among the isolates is limited to three types represented by strains Arkansas, 91HE17, and Sapulpa, respectively. These results indicate that the majority of the p28 genes are active genes and that antigenic variation of the E. chaffeensis 28-kDa proteins may result from differential expression of the p28 gene family members rather than gene conversion.

Alleles↗
PubMed1986

Further studies of cyclical transmission and antigenic variation of the ILDar 1 serodeme of Trypanosoma vivax.

Antigenic variation in the ILDar 1 serodeme of the naturally rodent-infective stock of West African Trypanosoma vivax has been investigated following cyclical transmission. The immunofluorescent and immune lysis tests were employed with a panel of 39 variant-specific mouse antisera. When antigenically homogeneous, or mixed, populations were transmitted by tsetse flies to goats, the first peak parasitaemias arising in the goats were antigenic mixtures (up to 9 major, and several minor variants being recognized in some cases) from which the ingested variant was absent. Although first peak parasitaemias in similarly infected goats showed some variants in common, there was no obvious relationship between the VAT profiles in different goats. When these populations were expanded in irradiated mice, VAT heterogeneity was maintained with a tendency towards the development of predominant variants in some, but not all, instances. Six additional variants, derived following the growth of bloodstream form ILDat 1.9 in 37 degrees C culture, were also represented in goat and mouse populations. Two further variants, isolated after cyclical development of ILDat 1.9-derived trypanosomes in vitro, were not present in the early parasitaemias in goats and mice.

Animals↗
PubMed1993

Shift in S-layer protein expression responsible for antigenic variation in Campylobacter fetus.

Campylobacter fetus strains possess regular paracrystalline surface layers (S-layers) composed of high-molecular-weight proteins and can change the size and crystalline structure of the predominant protein expressed. Polyclonal antisera demonstrate antigenic cross-reactivity among these proteins but suggest differences in epitopes. Monoclonal antibodies to the 97-kDa S-layer protein of Campylobacter fetus subsp. fetus strain 82-40LP showed three different reactivities. Monoclonal antibody 1D1 recognized 97-kDa S-layer proteins from all C. fetus strains studied; reactivity of monoclonal antibody 6E4 was similar except for epitopes in S-layer proteins from reptile strains and strains with type B lipopolysaccharide. Monoclonal antibody 2E11 only recognized epitopes on S-layer proteins from strains with type A lipopolysaccharide regardless of size. In vitro shift from a 97-kDa S-layer protein to a 127-kDa S-layer protein resulted in different reactivity, indicating that size change was accompanied by antigenic variation. To examine in vivo variation, heifers were genetically challenged with Campylobacter fetus subsp. venerealis strains and the S-layer proteins from sequential isolates were characterized. Analysis with monoclonal antibodies showed that antigenic reactivities of the S-layer proteins were varied, indicating that these proteins represent a system for antigenic variation.

Animals↗
PubMed1990

Impact on routine diagnosis of echovirus infections of intratypic differentiation and antigenic variation in echovirus type 25 studied by using monoclonal antibodies.

We studied the biological and antigenic properties of wild strains of echovirus type 25 isolated in France between 1982 and 1987 and compared them with the JV-4 prototype strains isolated in 1957. The wild strains differed from the prototype strain in their cellular tropism. The prototype strain grew readily in five cell lines (MRC5, MA 104, Vero, BGM, and HT 29-18), while for wild strains MRC5 and HT 29-18 cells were the most sensitive and supported growth to high titres (between 4.5 and 7.4 50% tissue culture infective doses per 0.05 ml). Plaques produced by wild strains were larger (6.05 +/- 0.94 mm in diameter [mean +/- standard deviation]) than those of the prototype strain (2.3 +/- 0.97 mm in diameter) and heterogeneous, even after cloning by three terminal dilution passages, which suggested heterogeneous virus populations. Virus neutralization with polyclonal monovalent sera showed that wild strains were significantly less neutralized by two reference immune sera than the prototype strain was. Monoclonal antibodies were raised against the echovirus type 25 JV-4 prototype strain. Nine clones with neutralizing activity were identified. Heterologous neutralizations of 14 clinical isolates revealed highly conserved, moderately conserved, and poorly conserved epitopes. The natural isolates differed from the prototype strain in two to four epitopes and can be classified into four different groups. We concluded that echovirus type 25, like coxsackie- and polioviruses, consists of heterogeneous viral populations with respect to biological and antigenic properties. In term of viral diagnosis, it may become increasingly difficult to identify recently isolated strains because of their antigenic variation.

Antibodies, Monoclonal↗
PubMed1988

DNA transformation leads to pilin antigenic variation in Neisseria gonorrhoeae.

Many pathogenic bacteria express pili (fimbriae) on their cell surfaces. These structures mediate binding of bacteria to host tissues, and may also be involved in other aspects of pathogenesis. Neisseria gonorrhoeae pili are mainly composed of a single protein, pilin, whose expression is controlled at chromosomal expression loci (pilE). An intact pilin gene and promoter sequences are only found at pilE. Strain MS11 contains two expression sites (pilE1 and pilE2), whereas several of its derivatives and other clinical isolates contain only one. Silent pilin loci (pilS1-pilS7) contain truncated variant pilin genes lacking the promoter and conserved pilin gene sequences. Pilin antigenic variation in N. gonorrhoeae occurs by DNA recombination between one of he silent partial variant gene segments in pilS and an expressed pilin gene in pilE. The recombination reactions are nonreciprocal, and therefore the mechanism has been classified as gene conversion. We report that much of the recombination between pilin loci actually occurs after transformation of living piliated cells by DNA liberated from lysed cells within a population. This constitutes a new molecular mechanism for an antigenic variation system, as well as the first specific function for a DNA transformation system.

Antigenic Variation↗
PubMed2004

Investigating antigenic variation and other parasite-host interactions in Plasmodium falciparum infections in naïve hosts.

Mathematical models of the in-host dynamics of malaria infections provide a valuable tool to explore aspects of the host-parasite interaction that are not possible to investigate experimentally. This paper presents predictions of several important parameter values for 2 parasite strains/groups: parasite PfEMP1 switching rates, dynamics of host anti-PfEMP1 antibodies and parameters related to specific and non-specific host immune responses. A stochastic simulation model of the in-host dynamics of Plasmodium falciparum infections in naïve hosts was used to make these predictions. This model incorporates a novel process to simulate antigenic variation by the parasite, and specific and non-specific immune responses by the host. Comparison of model output to a range of published statistics indicated that the model is capable of reproducing the features of clinical P. falciparum infections, including the characteristic recrudescent behaviour. Using the model, we explored the hypothesized switching mechanism of a fast overall rate of antigenic variation early in an infection and found that it is compatible with chronic infections when the var genes are split into 2 groups; fast and slow switching.

Animals↗
PubMed1997

A modification in restriction pattern of the Plasmodium falciparum Pf60 multigene family associated with a specific antigenic variation switch in the Palo Alto line.

The wide occurrence of molecular rearrangements associated with expression of specific members within multigene families led us to investigate whether this also happens during antigenic variation of malaria parasites. We have investigated here the Pf60 multigene family restriction patterns of four distinct variants of the Plasmodium falciparum Palo Alto line propagated in Saimiri monkeys. The O and its cloned Oc variant both express the O serotype, while the R variant (derived from O parasites) and the Vc variant (derived from Oc parasites) express distinct serotypes. We show that a specific modification of the restriction pattern could be associated with antigenic switching in this line. The DNA of the variants which expressed the O serotype (O and Oc) had a specific 5.5 kb Hind III/Eco RI restriction fragment which was absent from the R or Vc parasite DNA, whereas both R and Vc DNA presented a 3.5 kb Hind III/Eco RI restriction fragment, which was absent from the O and Oc parasites. These results indicate that both expression and silencing of the O serotype were associated with specific restriction patterns, suggesting that some molecular rearrangement or some modification of the DNA might control expression of the variant surface antigen in malaria parasites.

Animals↗