Multiple Overlapping Epitopes in the Repetitive Unit of the Shed Acute-Phase Antigen from
            <i>Trypanosoma cruzi</i>
            Enhance Its Immunogenic Properties

Álvarez, Paula Fernández; Leguizamón, María Susana; Buscaglia, Carlos A.; Pitcovsky, Tamara A.; Campetella, Oscar

doi:10.1128/iai.69.12.7946-7949.2001

Cited by 32 publications

(40 citation statements)

References 22 publications

(15 reference statements)

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“…Moreover, ϳ80% of the reactive serum samples (36/46) showed similar antibody titers toward either molecule (i.e., ⌬ absorbance values, Ͻ25%; data not shown). TSSA-CL [24][25][26][27][28][29][30][31][32][33][34][35][36][37][38] and TSSA-CL 48-62 , on the other hand, yielded negative results for every serum sample tested (Fig. 1C).…”

Section: Resultsmentioning

confidence: 99%

“…TSSA-CL [48][49][50][51][52][53][54][55][56][57][58][59][60][61][62] matched the sequence of p48-62 in the chip array, which was also recorded as negative for both IgG samples (see Table S3 in the supplemental material). In the case of TSSA-CL [24][25][26][27][28][29][30][31][32][33][34][35][36][37][38] , however, its matching peptide (p24-38) was recorded as positive for both IgG samples in our chip assay (see Table S3). Despite this discrepancy, which can be attributed to a higher sensitivity of the microarray, our data showed a close agreement between the two kinds of assays (peptide-chip arrays and GST-fusion protein-based ELISA).…”

Section: Resultsmentioning

confidence: 99%

“…The glutathione S-transferase (GST)-fusion protein bearing the repetitive domain of T. cruzi shed acute-phase antigen (SAPA) has been described (26,27). The GST fusion protein bearing the central region (from residues 24 to 61/62) of Sylvio X-10 TSSA (TSSASy ) and CL Brener TSSA (TSSA-CL 24-62 ) have also been described (11).…”

Section: Methodsmentioning

confidence: 99%

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Mapping Antigenic Motifs in the Trypomastigote Small Surface Antigen from Trypanosoma cruzi

Balouz

Camara

Canepa

et al. 2015

Clin. Vaccine Immunol.

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The trypomastigote small surface antigen (TSSA) is a mucin-like molecule from Trypanosoma cruzi, the etiological agent of Chagas disease, which displays amino acid polymorphisms in parasite isolates. TSSA expression is restricted to the surface of infective cell-derived trypomastigotes, where it functions as an adhesin and engages surface receptors on the host cell as a prerequisite for parasite internalization. Previous results have established TSSA-CL, the isoform encoded by the CL Brener clone, as an appealing candidate for use in serology-based diagnostics for Chagas disease. Here, we used a combination of peptide-and recombinant protein-based tools to map the antigenic structure of TSSA-CL at maximal resolution. Our results indicate the presence of different partially overlapping B-cell epitopes clustering in the central portion of TSSA-CL, which contains most of the polymorphisms found in parasite isolates. Based on these results, we assessed the serodiagnostic performance of a 21-amino-acidlong peptide that spans TSSA-CL major antigenic determinants, which was similar to the performance of the previously validated glutathione S-transferase (GST)-TSSA-CL fusion molecule. Furthermore, the tools developed for the antigenic characterization of the TSSA antigen were also used to explore other potential diagnostic applications of the anti-TSSA humoral response in Chagasic patients. Overall, our present results provide additional insights into the antigenic structure of TSSA-CL and support this molecule as an excellent target for molecular intervention in Chagas disease. Chagas disease is a major health and economic problem in Latin America, for which no vaccine or appropriate drugs for largescale public health interventions are yet available (1). It is caused by the protozoan Trypanosoma cruzi, found throughout the American continents in a variety of wild and domestic mammalian reservoirs, and it is transmitted by the bite of infected bloodsucking triatomine bugs. It is estimated that 8 to 10 million people are currently infected with T. cruzi and that up to 120 million individuals living in areas that are endemic for the parasite are at risk of infection (1). Increasing travel and immigration have also brought the risk of T. cruzi infection into countries that are not endemic for the parasite (2). Several efforts have successfully been undertaken to control transmission in Latin America, with a concomitant decrease in the actual numbers of acute vector-borne infections (3). However, humans can also become infected with T. cruzi through the ingestion of tainted food and fluids, receipt of contaminated blood transfusion or organ transplantation, and from mother-to-child during pregnancy/delivery (4).The diagnosis of Chagas disease is challenging because it is often asymptomatic in its acute phase and evolves into a chronic stage in which the disease course takes different clinical forms (1). In addition, and due to a major decline in parasitemia during the chronic phase, the detection of T. cruzi in blood sample...

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Mapping Antigenic Motifs in the Trypomastigote Small Surface Antigen from Trypanosoma cruzi

Balouz

Camara

Canepa

et al. 2015

Clin. Vaccine Immunol.

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“…We describe the use of a random peptide phage display library to identify immunogenic proteins from P. aeruginosa. The use of phage display for the identification of immunogenic proteins has been demonstrated to be useful for development of vaccines against human diseases such as cancer (17,38,39) and many diverse human pathogens, including Neisseria meningitides (28,22,27), Echinococcus granulosus (21), and Trypanosoma cruzi (2). However, the use of a random peptide phage display library rather than a recombinant library made with DNA from the pathogen of interest is a novel technique that has been used in N. meningitidis to identify mimotopes of nonpeptide antigens (28).…”

Section: Discussionmentioning

confidence: 99%

Use of Phage Display To Identify Potential Pseudomonas aeruginosa Gene Products Relevant to Early Cystic Fibrosis Airway Infections

et al. 2005

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Pseudomonas aeruginosa airway infections are a major cause of morbidity and mortality in patients with cystic fibrosis. Treatment of established infections is difficult, even with microbiologically active agents. Thus, prevention of infection is an important goal of management. Isolates from cystic fibrosis patients appear to originate from the environment but adapt to the milieu of the airway of the cystic fibrosis patient and evolve toward a common phenotype. Identification of the antigens expressed early in infection may lead to novel targets for vaccine development. Immunogenic peptides were identified in a J404 random nonapeptide phage display library with serum from cystic fibrosis patients obtained within the first year of P. aeruginosa infection. One hundred sixty-five reactive clones were verified by plaque lift assays, and their inserts were sequenced. The sequenced nonapeptides were compared with the published sequence of strain PAO1, identifying homologies to 76 genes encoding outer membrane and secreted proteins. The majority of these were proteins involved in small-molecule transport, membrane structural proteins, and secreted factors. An in silico analysis was performed that suggested that the occurrence of multiple matches to predominantly outer membrane and secreted proteins was not attributable to random chance. Finally, gene expression array data from early isolates of P. aeruginosa from cystic fibrosis patients was compared with the results from phage display analysis. Eleven outer membrane and secreted proteins were common between the two data sets. These included genes involved in iron acquisition, antibiotic efflux, fimbrial biogenesis, and pyocin synthesis. These results demonstrate the feasibility and validity of this novel approach and suggest potential targets for future development.

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“…Natural humoral responses to many T. cruzi antigens appear to be directed to epitopes encoded by these repeat units. It has been suggested that the immune response to parasite repetitive antigens does not protect the host because it masks the host's immune response to more critical epitopes on different molecules (1,2,6,10,14).…”

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confidence: 99%

Mapping of B-Cell Epitopes in a Trypanosoma cruzi Immunodominant Antigen Expressed in Natural Infections

Lesénéchal

Becquart

Lacoux

et al. 2005

Clin Vaccine Immunol

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Tc40 is an immunodominant antigen present in natural Trypanosoma cruzi infections. This immunogen was thoroughly mapped by using overlapping amino acid sequences identified by gene cloning and chemical peptide synthesis. To map continuous epitopes of the Tc40 antigen, an epitope expression library was constructed and screened with sera from human chagasic patients. A major, linear B-cell epitope spanning residues 403 to 426 (PAKAAAPPAA) was identified in the central domain of Tc40. A synthetic peptide spanning this region reacted strongly with 89.8% of the serum samples from T. cruzi-infected individuals. This indicates that the main antigenic site is defined by the linear sequence of the peptide rather than a conformation-dependent structure. The major B-cell epitope of Tc40 shares a high degree of sequence identity with T. cruzi ribosomal and RNA binding proteins, suggesting the existence of cross-reactivity among these molecules.

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Multiple Overlapping Epitopes in the Repetitive Unit of the Shed Acute-Phase Antigen from Trypanosoma cruzi Enhance Its Immunogenic Properties

Cited by 32 publications

References 22 publications

Mapping Antigenic Motifs in the Trypomastigote Small Surface Antigen from Trypanosoma cruzi

Mapping Antigenic Motifs in the Trypomastigote Small Surface Antigen from Trypanosoma cruzi

Use of Phage Display To Identify Potential Pseudomonas aeruginosa Gene Products Relevant to Early Cystic Fibrosis Airway Infections

Mapping of B-Cell Epitopes in a Trypanosoma cruzi Immunodominant Antigen Expressed in Natural Infections

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