Complexity of the major surface protease (msp) gene organization inLeishmania (Viannia) braziliensis: evolutionary and functional implications

Parasitology ◽  
2005 ◽  
Vol 131 (2) ◽  
pp. 207-214 ◽  
Author(s):  
K. VICTOIR ◽  
J. AREVALO ◽  
S. DE DONCKER ◽  
D. C. BARKER ◽  
T. LAURENT ◽  
...  
Keyword(s):  
Gene Families ◽  
Adaptive Strategy ◽  
Gene Organization ◽  
Point Of View ◽  
T Cell Epitopes ◽  
Conserved Sequence ◽  
Functional Implications ◽  
Surface Domains ◽  
Major Surface ◽  
Host Parasite

The major surface protease (msp orgp63) ofLeishmaniaplays a major role in the host–parasite interaction. We analysed here the structure of the msp gene locus inLeishmania (Viannia) braziliensisand compared it to results obtained in other species. Physical mapping of cosmid contigs revealed a minimum of 37 genes per haploid genome and at least 8 different msp gene families. Within the same organism, these genes showed a nucleotide sequence varying in certain stretches from 3 to 34%, and a mosaic structure. From an evolutionary point of view, major differences were observed between subgeneraVianniaandLeishmania, both in terms of msp gene number and sequence. Within subgenusViannia, phenetic analysis revealed three clusters in which sequence variants ofL. (Viannia) braziliensisandL. (Viannia) guyanensiswere interspersed. Functional implications of our results were explored from predictedL. (Viannia) braziliensisprotein sequences: regions encoding the msp catalytic site showed a conserved sequence, while regions encoding surface domains possibly involved in the host–parasite interaction (macrophage adhesion sites and immunodominant B-cell and T-cell epitopes) were variable. We speculate that this would be an adaptive strategy of the parasite.

scholarly journals Anaplasma marginale Major Surface Protein 2 CD4+-T-Cell Epitopes Are Evenly Distributed in Conserved and Hypervariable Regions (HVR), Whereas Linear B-Cell Epitopes Are Predominantly Located in the HVR

2004 ◽  
Vol 72 (12) ◽  
pp. 7360-7366 ◽  
Author(s):  
Jeffrey R. Abbott ◽  
Guy H. Palmer ◽  
Chris J. Howard ◽  
Jayne C. Hope ◽  
Wendy C. Brown
Keyword(s):  
T Cell ◽  
B Cell ◽  
Surface Protein ◽  
Anaplasma Marginale ◽  
T Cell Epitopes ◽  
B Cell Epitopes ◽  
Major Surface Protein ◽  
Hypervariable Regions ◽  
Major Surface ◽  
Linear B

ABSTRACT Organisms in the genus Anaplasma express an immunodominant major surface protein 2 (MSP2), composed of a central hypervariable region (HVR) flanked by highly conserved regions. Throughout Anaplasma marginale infection, recombination results in the sequential appearance of novel MSP2 variants and subsequent control of rickettsemia by the immune response, leading to persistent infection. To determine whether immune evasion and selection for variant organisms is associated with a predominant response against HVR epitopes, T-cell and linear B-cell epitopes were localized by measuring peripheral blood gamma interferon-secreting cells, proliferation, and antibody binding to 27 overlapping peptides spanning MSP2 in 16 cattle. Similar numbers of MSP2-specific CD4+ T-cell epitopes eliciting responses of similar magnitude were found in conserved and hypervariable regions. T-cell epitope clusters recognized by the majority of animals were identified in the HVR (amino acids [aa] 171 to 229) and conserved regions (aa 101 to 170 and 272 to 361). In contrast, linear B-cell epitopes were concentrated in the HVR, residing within hydrophilic sequences. The pattern of recognition of epitope clusters by T cells and of HVR epitopes by B cells is consistent with the influence of protein structure on epitope recognition.

scholarly journals In Silico Prediction of T and B Cell Epitopes of SAG1-Related Sequence 3 (SRS3) Gene for Developing Toxoplasma gondii Vaccine

2020 ◽  
Vol In Press (In Press) ◽  
Author(s):  
Abolfazl Mirzadeh ◽  
Geita Saadatnia ◽  
Majid Golkar ◽  
Jalal Babaie ◽  
Samira Amiri ◽  
...  
Keyword(s):  
Toxoplasma Gondii ◽  
Dna Vaccine ◽  
In Silico ◽  
Effective Vaccine ◽  
T Cell Epitopes ◽  
In Silico Prediction ◽  
Vaccine Strategy ◽  
Related Sequence ◽  
Ideal Tool ◽  
Major Surface

: Toxoplasmosis is a worldwide infection that can lead to serious problems in immune-compromised individuals and fetuses. A DNA vaccine strategy would be an ideal tool against Toxoplasma gondii. One of the necessary measures to provide an effective vaccine is the selection of proteins with high antigenicity. The SAG1-related sequence 3 (SRS3) protein is a major surface antigen in T. gondii that can be used as a vaccine candidate. In the present study, bioinformatics and computational methods were utilized to predict protein characteristics, as well as secondary and tertiary structures. The in silico approach is highly suited to analyze, design, and evaluate DNA vaccine strategies. Hence, in silico prediction was used to identify B and T cell epitopes and compare the antigenicity of SRS3 and other candidate genes of Toxoplasma previously applied in the production of vaccines. The results of the analysis theoretically showed that SRS3 has multiple epitopes with high antigenicity, proposing that SRS3 is a promising immunogenic candidate for the development of DNA vaccines against toxoplasmosis.

Evolution and function of tandem repeats in the major surface protein 1a of the ehrlichial pathogenAnaplasma marginale

2001 ◽  
Vol 2 (2) ◽  
pp. 163-174 ◽  
Author(s):  
José de la Fuente ◽  
Jose C. Garcia-Garcia ◽  
Edmour F. Blouin ◽  
Sergio D. Rodríguez ◽  
Migel A. García ◽  
...  
Keyword(s):  
Tandem Repeats ◽  
Control Strategies ◽  
Surface Protein ◽  
Single Copy ◽  
Major Surface Protein ◽  
Host Parasite Interactions ◽  
Major Surface ◽  
And Function ◽  
Host Parasite ◽  
Bovine Erythrocytes

AbstractThe major surface protein (MSP) 1a of the ehrlichial cattle pathogenAnaplasma marginale, encoded by the single-copy genemsp1α, has been shown to have a neutralization-sensitive epitope and to be an adhesin for bovine erythrocytes and tick cells.msp1αhas been found to be a stable genetic marker for the identification of geographic isolates ofA. marginalethroughout development in acutely and persistently infected cattle and in ticks. The molecular weight of MSP1a varies among geographic isolates ofA. marginalebecause of a varying number of tandemly repeated peptides of 28–29 amino acids. Variation in the sequence of the tandem repeats occurs within and among isolates, and may have resulted from evolutionary pressures exerted by ligand–receptor and host–parasite interactions. These repeated sequences include markers for tick transmissibility that may be important in the identification of ehrlichial pathogens because they may influence control strategies and the design of subunit vaccines.

scholarly journals Evolution of the T-Cell Receptor (TR) Loci in the Adaptive Immune Response: The Tale of the TRG Locus in Mammals

Genes ◽  
2020 ◽  
Vol 11 (6) ◽  
pp. 624 ◽  
Author(s):  
Rachele Antonacci ◽  
Serafina Massari ◽  
Giovanna Linguiti ◽  
Anna Caputi Jambrenghi ◽  
Francesco Giannico ◽  
...  
Keyword(s):  
Immune Response ◽  
Genomic Organization ◽  
Mammalian Species ◽  
Adaptive Immune Response ◽  
Gene Families ◽  
Cell Receptor ◽  
Gene Organization ◽  
Cell Mediated Immunity ◽  
Gene Repertoire ◽  
Trg Locus

T lymphocytes are the principal actors of vertebrates’ cell-mediated immunity. Like B cells, they can recognize an unlimited number of foreign molecules through their antigen-specific heterodimer receptors (TRs), which consist of αβ or γδ chains. The diversity of the TRs is mainly due to the unique organization of the genes encoding the α, β, γ, and δ chains. For each chain, multi-gene families are arranged in a TR locus, and their expression is guaranteed by the somatic recombination process. A great plasticity of the gene organization within the TR loci exists among species. Marked structural differences affect the TR γ (TRG) locus. The recent sequencing of multiple whole genome provides an opportunity to examine the TR gene repertoire in a systematic and consistent fashion. In this review, we report the most recent findings on the genomic organization of TRG loci in mammalian species in order to show differences and similarities. The comparison revealed remarkable diversification of both the genomic organization and gene repertoire across species, but also unexpected evolutionary conservation, which highlights the important role of the T cells in the immune response.

scholarly journals Physical Linkage of Naturally Complexed Bacterial Outer Membrane Proteins Enhances Immunogenicity

2007 ◽  
Vol 76 (3) ◽  
pp. 1223-1229 ◽  
Author(s):  
Henriette Macmillan ◽  
Junzo Norimine ◽  
Kelly A. Brayton ◽  
Guy H. Palmer ◽  
Wendy C. Brown
Keyword(s):  
T Cell ◽  
Membrane Proteins ◽  
Outer Membrane ◽  
Outer Membrane Proteins ◽  
Surface Protein ◽  
Host Cells ◽  
Effective Vaccine ◽  
T Cell Epitopes ◽  
Carrier Effect ◽  
Major Surface

ABSTRACTThe outer membrane proteins (OMPs) of bacterial pathogens are essential for their growth and survival and especially for attachment and invasion of host cells. Since the outer membrane is the interface between the bacterium and the host cell, outer membranes and individual OMPs are targeted for development of vaccines against many bacterial diseases. Whole outer membrane fractions often protect against disease, and this protection cannot be fully reproduced by using individual OMPs. Exactly how the interactions among individual OMPs influence immunity is not well understood. We hypothesized that one OMP rich in T-cell epitopes can act as a carrier for an associated OMP which is poor in T-cell epitopes to generate T-dependent antibody responses, similar to the hapten-carrier effect. Major surface protein 1a (MSP1a) and MSP1b1 occur as naturally complexed OMPs in theAnaplasma marginaleouter membrane. Previous studies demonstrated that immunization with the native MSP1 heteromer induced strong immunoglobulin G (IgG) responses to both proteins, but only MSP1a stimulated strong CD4+T-cell responses. Therefore, to test our hypothesis, constructs of CD4+T-cell epitopes from MSP1a linked to MSP1b1 were compared with individually administered MSP1a and MSP1b1 for induction of MSP1b-specific IgG. By linking the T-cell epitopes from MSP1a to MSP1b1, significantly higher IgG titers against MSP1b1 were induced. Understanding how the naturally occurring intermolecular interactions between OMPs influence the immune response may lead to more effective vaccine design.

scholarly journals Major Histocompatibility Complex Class II DR-Restricted Memory CD4+ T Lymphocytes Recognize Conserved Immunodominant Epitopes of Anaplasma marginale Major Surface Protein 1a

2002 ◽  
Vol 70 (10) ◽  
pp. 5521-5532 ◽  
Author(s):  
Wendy C. Brown ◽  
Travis C. McGuire ◽  
Waithaka Mwangi ◽  
Kimberly A. Kegerreis ◽  
Henriette Macmillan ◽  
...  
Keyword(s):  
T Cells ◽  
Major Histocompatibility Complex ◽  
T Cell ◽  
Protective Immunity ◽  
Surface Protein ◽  
T Cell Epitopes ◽  
Major Surface Protein ◽  
Histocompatibility Complex ◽  
Cell Clones ◽  
Major Surface

ABSTRACT Native major surface protein 1 (MSP1) of Anaplasma marginale, composed of covalently associated MSP1a and MSP1b proteins, stimulates protective immunity in cattle against homologous and heterologous strain challenge. Protective immunity against pathogens in the family Anaplasmataceae involves both CD4+ T cells and neutralizing immunoglobulin G. Thus, an effective vaccine should contain both CD4+ T- and B-lymphocyte epitopes that will elicit strong memory responses upon infection with homologous and heterologous strains. Previous studies demonstrated that the predominant CD4+ T-cell response in MSP1 vaccinates is directed against the MSP1a subunit. The present study was designed to identify conserved CD4+ T-cell epitopes in MSP1a presented by a broadly represented subset of major histocompatibility complex (MHC) class II molecules that would be suitable for inclusion in a recombinant vaccine. Transmembrane protein prediction analysis of MSP1a from the Virginia strain revealed a large hydrophilic domain (HD), extending from amino acids (aa) 1 to 366, and a hydrophobic region extending from aa 367 to 593. The N terminus (aa 1 to 67) includes one 28-aa form A repeat and one 29-aa form B repeat, which each contain an antibody neutralization-sensitive epitope [Q(E)ASTSS]. In MSP1 vaccinates, recombinant MSP1a HD (aa 1 to 366) stimulated recall proliferative responses that were comparable to those against whole MSP1a excluding the repeat region (aa 68 to 593). Peptide mapping determined a minimum of five conserved epitopes in aa 151 to 359 that stimulated CD4+ T cells from cattle expressing DR-DQ haplotypes common in Holstein-Friesian breeds. Peptides representing three epitopes (aa 231 to 266, aa 270 to 279, and aa 290 to 319) were stimulatory for CD4+ T-cell clones and restricted by DR. A DQ-restricted CD4+ T-cell epitope, present in the N-terminal form B repeat (VSSQSDQASTSSQLG), was also mapped using T-cell clones from one vaccinate. Although form B repeat-specific T cells did not recognize the form A repeat peptide (VSSQS_EASTSSQLG), induction of T-cell anergy by this peptide was ruled out. The presence of multiple CD4+ T-cell epitopes in the MSP1a HD, in addition to the neutralization-sensitive epitope, supports the testing of this immunogen for induction of protective immunity against A. marginale challenge.

scholarly journals Identification of a Putative Precursor to the Major Surface Glycoprotein of Pneumocystis carinii

1998 ◽  
Vol 66 (2) ◽  
pp. 741-746 ◽  
Author(s):  
Susan M. Sunkin ◽  
Michael J. Linke ◽  
Francis X. McCormack ◽  
Peter D. Walzer ◽  
James R. Stringer
Keyword(s):  
Insect Cells ◽  
Pneumocystis Carinii ◽  
Recombinant Baculovirus ◽  
Polyclonal Antiserum ◽  
Surface Glycoprotein ◽  
Messenger Rnas ◽  
Conserved Sequence ◽  
Amino Acid Peptide ◽  
Major Surface Glycoprotein ◽  
Major Surface

ABSTRACT The major surface glycoprotein (MSG) of Pneumocystis cariniif. sp. carinii is a family of proteins encoded by a family of heterogeneous genes. Messenger RNAs encoding different MSGs each begin with the same 365-bp sequence, called the Upstream Conserved Sequence (UCS), which is in frame with the contiguous MSG sequence. The UCS contains several potential start sites for translation. To determine if translation of MSG mRNAs begins in the UCS, polyclonal antiserum was raised against the 123-amino-acid peptide encoded by the UCS. The anti-UCS serum reacted with a P. carinii protein that migrated at 170 kDa; however, it did not react with the mature MSG protein, which migrates at 116 kDa. A 170-kDa protein was immunoprecipitated with anti-UCS serum and shown to react with a monoclonal antibody against a conserved MSG epitope. To explore the functional role of the UCS in the trafficking of MSG, the nucleotide sequence encoding the UCS peptide was ligated to the 5′ end of an MSG gene and incorporated into a recombinant baculovirus. Insect cells infected with the UCS-MSG hybrid gene expressed a 160-kDa protein which was N-glycosylated. By contrast, insect cells infected with a baculovirus carrying an MSG gene lacking the UCS expressed a nonglycosylated 130-kDa protein. These data suggest that in P. carinii, translation begins in the UCS to produce a pre-MSG protein, which is subsequently directed to the endoplasmic reticulum and processed to the mature form by proteolytic cleavage.

scholarly journals Gene Duplication and Gain in the Trematode Atriophallophorus Winterbourni Contributes to Adaptation to Parasitism

2021 ◽  
Author(s):  
Natalia Zajac ◽  
Stefan Zoller ◽  
Katri Seppälä ◽  
David Moi ◽  
Christophe Dessimoz ◽  
...  
Keyword(s):  
De Novo ◽  
Genomic Analysis ◽  
Enrichment Analysis ◽  
Gene Families ◽  
Comparative Genomic ◽  
Genomic Changes ◽  
Go Enrichment ◽  
Duplication Events ◽  
Parasitic Lifestyle ◽  
Host Parasite

Abstract Gene duplications and novel genes have been shown to play a major role in helminth adaptation to a parasitic lifestyle because they provide the novelty necessary for adaptation to a changing environment, such as living in multiple hosts. Here we present the de novo sequenced and annotated genome of the parasitic trematode Atriophallophorus winterbourni and its comparative genomic analysis to other major parasitic trematodes. First, we reconstructed the species phylogeny, and dated the split of A. winterbourni from the Opisthorchiata suborder to approximately 237.4 MYA (± 120.4 MY). We then addressed the question of which expanded gene families and gained genes are potentially involved in adaptation to parasitism. To do this, we used Hierarchical Orthologous Groups to reconstruct three ancestral genomes on the phylogeny leading to A. winterbourni and performed a GO enrichment analysis of the gene composition of each ancestral genome, allowing us to characterize the subsequent genomic changes. Out of the 11,499 genes in the A. winterbourni genome, as much as 24% have arisen through duplication events since the speciation of A. winterbourni from the Opisthorchiata, and as much as 31.9% appear to be novel, i.e. newly acquired. We found 13 gene families in A. winterbourni to have had more than 10 genes arising through these recent duplications; all of which have functions potentially relating to host behavioural manipulation, host tissue penetration, and hiding from host immunity through antigen presentation. We identified several families with genes evolving under positive selection. Our results provide a valuable resource for future studies on the genomic basis of adaptation to parasitism and point to specific candidate genes putatively involved in antagonistic host-parasite adaptation.

Survey of the endohelminth parasites of freshwater fishes in the upper Mezquital River Basin, Durango State, Mexico

Zootaxa ◽  
2009 ◽  
Vol 2164 (1) ◽  
pp. 1-20 ◽  
Author(s):  
G. PÉREZ-PONCE DE LEÓN ◽  
R. ROSAS-VALDEZ ◽  
B. MENDOZA-GARFIAS ◽  
R. AGUILAR-AGUILAR ◽  
J. FALCÓN-ORDAZ ◽  
...  
Keyword(s):  
River Basin ◽  
Fish Fauna ◽  
Freshwater Fishes ◽  
Point Of View ◽  
Helminth Parasites ◽  
Northern Mexico ◽  
Transitional Area ◽  
Freshwater Fish Fauna ◽  
New Hosts ◽  
Host Parasite

As a part of an ongoing inventory of the helminth parasites of freshwater fishes in Mexico, 676 specimens were collected between November 2007 and December 2008 in 23 localities along the upper Mezquital River Basin in Durango State, northern Mexico. Sixteen species of hosts, mostly corresponding to Nearctic freshwater elements, were studied. A total of 1,230 individual worms were collected during this survey, representing 25 species of endohelminths of which 9 were digeneans, 3 were cestodes, 4 were acanthocephalans, and 9 were nematodes. The checklist contains 24 new hosts and 42 new locality records. The information provided in this checklist may be helpful for our understanding of the biodiversity and historical biogeography of this host-parasite system, since the Mezquital River Basin mostly contains a Nearctic freshwater fish fauna, with a few Neotropical and endemic elements and may represent a transitional area from a biogeographical point of view.

scholarly journals Evolution of Host Specificity by Malaria Parasites through Altered Mechanisms Controlling Genome Maintenance

mBio ◽  
2020 ◽  
Vol 11 (2) ◽  
Author(s):  
Michelle C. Siao ◽  
Janus Borner ◽  
Susan L. Perkins ◽  
Kirk W. Deitsch ◽  
Laura A. Kirkman
Keyword(s):  
Gene Family ◽  
Family Members ◽  
Gene Families ◽  
Genome Integrity ◽  
Human Populations ◽  
Protozoan Parasites ◽  
Malaria Parasites ◽  
Content Type ◽  
Ectopic Recombination ◽  
Host Parasite

ABSTRACT The protozoan parasites that cause malaria infect a wide variety of vertebrate hosts, including birds, reptiles, and mammals, and the evolutionary pressures inherent to the host-parasite relationship have profoundly shaped the genomes of both host and parasite. Here, we report that these selective pressures have resulted in unexpected alterations to one of the most basic aspects of eukaryotic biology, the maintenance of genome integrity through DNA repair. Malaria parasites that infect humans continuously generate genetic diversity within their antigen-encoding gene families through frequent ectopic recombination between gene family members, a process that is a crucial feature of the persistence of malaria globally. The continuous generation of antigen diversity ensures that different parasite isolates are antigenically distinct, thus preventing extensive cross-reactive immunity and enabling parasites to maintain stable transmission within human populations. However, the molecular basis of the recombination between gene family members is not well understood. Through computational analyses of the antigen-encoding, multicopy gene families of different Plasmodium species, we report the unexpected observation that malaria parasites that infect rodents do not display the same degree of antigen diversity as observed in Plasmodium falciparum and appear to undergo significantly less ectopic recombination. Using comparative genomics, we also identify key molecular components of the diversification process, thus shedding new light on how malaria parasites balance the maintenance of genome integrity with the requirement for continuous genetic diversification. IMPORTANCE Malaria remains one of the most prevalent and deadly infectious diseases of the developing world, causing approximately 228 million clinical cases and nearly half a million deaths annually. The disease is caused by protozoan parasites of the genus Plasmodium, and of the five species capable of infecting humans, infections with P. falciparum are the most severe. In addition to the parasites that infect people, there are hundreds of additional species that infect birds, reptiles, and other mammals, each exquisitely evolved to meet the specific challenges inherent to survival within their respective hosts. By comparing the unique strategies that each species has evolved, key insights into host-parasite interactions can be gained, including discoveries regarding the pathogenesis of human disease. Here, we describe the surprising observation that closely related parasites with different hosts have evolved remarkably different methods for repairing their genomes. This observation has important implications for the ability of parasites to maintain chronic infections and for the development of host immunity.

Sign in / Sign up

Export Citation Format

Share Document