Cellular immune responses to recombinant <i>Plasmodium vivax</i> tryptophan‐rich antigen (PvTRAg) among individuals exposed to vivax malaria

Alam, Mohammad Tauqeer; Bora, Hema; Mittra, Pooja; Singh, Neeru; Sharma, Yagya D.

doi:10.1111/j.1365-3024.2008.01033.x

Cited by 13 publications

(7 citation statements)

References 30 publications

(41 reference statements)

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“…These Plasmodium vivax tryptophan-rich proteins are expressed during blood stages of the parasite [24]–[27], [29]. Some of them, e.g.…”

Section: Discussionmentioning

confidence: 99%

“…Expression and purification of some of these PvTRAgs have previously been described [24], [26], [28]–[30]. Remaining PvTRAgs were cloned and expressed using the methods described elsewhere [23].…”

Section: Methodsmentioning

confidence: 99%

“…These proteins have high percentage of tryptophan residues which are positionally conserved [23]. Many of them have been immunologically characterized where they induced significant cellular and humoral responses in human individuals, and showed very little genetic polymorphism in parasite population [24]–[30]. One of them has also been shown to bind to human erythrocytes [31].…”

Section: Introductionmentioning

confidence: 99%

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Erythrocyte Binding Activity Displayed by a Selective Group of Plasmodium vivax Tryptophan Rich Antigens Is Inhibited by Patients’ Antibodies

Tyagi

Sharma

2012

PLoS ONE

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Plasmodium vivax is a very common but non-cultivable malaria parasite affecting large human population in tropical world. To develop therapeutic reagents for this malaria, the parasite molecules involved in host-parasite interaction need to be investigated as they form effective vaccine or drug targets. We have investigated here the erythrocyte binding activity of a group of 15 different Plasmodium vivax tryptophan rich antigens (PvTRAgs). Only six of them, named PvTRAg, PvTRAg38, PvTRAg33.5, PvTRAg35.2 PvTRAg69.4 and PvATRAg74, showed binding to host erythrocytes. That the PvTRAgs binding to host erythrocytes was specific was evident from the competitive inhibition and saturation kinetics results. The erythrocyte receptors for these six PvTRAgs were resistant to trypsin and neuraminidase. These receptors were also chymotrypsin resistant except the receptors for PvTRAg38 and PvATRAg74 which were partially sensitive to this enzyme. The cross-competition studies showed that the chymotrypsin resistant RBC receptor for each of these two proteins was different. Altogether, there seems to be three RBC receptors for these six PvTRAgs and each PvTRAg has two RBC receptors. Both RBC receptors for PvTRAg, PvTRAg69.4, PvTRAg33.5, and PvTRAg35.2 were common to all these four proteins. These four PvTRAgs also shared one of their RBC receptors with PvTRAg38 as well as with PvATRAg74. The erythrocyte binding activity of these six PvTRAgs was inhibited by the respective rabbit polyclonal antibodies as well as by the natural antibodies produced by the P. vivax exposed individuals. It is concluded that only selective few PvTRAgs show erythrocyte binding activity involving different receptor molecules which can be blocked by the natural antibodies. Further studies on these receptor and ligands may lead to the development of therapeutic reagents for P. vivax malaria.

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“…These Plasmodium vivax tryptophan-rich proteins are expressed during blood stages of the parasite [24]–[27], [29]. Some of them, e.g.…”

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Erythrocyte Binding Activity Displayed by a Selective Group of Plasmodium vivax Tryptophan Rich Antigens Is Inhibited by Patients’ Antibodies

Tyagi

Sharma

2012

PLoS ONE

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“…Tryptophan‐rich proteins of P. vivax belong to ‘Pv‐fam‐a’ family and there is a stage‐specific expression of these proteins in the parasite, probably to perform different functions . Previously, we immunobiologically characterized large numbers of these proteins and hypothesized that some of them may be involved in red cell invasion . These proteins have exceptionally high tryptophan contents and the tryptophan residues are positionally conserved with a certain spatial pattern.…”

mentioning

confidence: 99%

Host–parasite interaction: multiple sites in the Plasmodium vivax tryptophan‐rich antigen PvTRAg38 interact with the erythrocyte receptor band 3

et al. 2016

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Tryptophan-rich antigens of malarial parasites interact with host molecules and play an important role in parasite survival. Merozoite expressed Plasmodium vivax tryptophan-rich antigen PvTRAg38 binds to human erythrocytes and facilitates parasite growth in a heterlologous Plasmodium falciparum culture system. Recently, we identified band 3 in human erythrocytes as one of its receptors, although the receptor-ligand binding mechanisms remain unknown. In the present study, using synthetic mutated peptides of PvTRAg38, we show that multiple amino acid residues of its 12 amino acid domain (KWVQWKNDKIRS) at position 197-208 interact with three different ectodomains of band 3 receptor on human erythrocytes. Our findings may help in the design of new therapeutic approaches for malaria.

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“…These proteins need to be characterized so as to develop them as the drug or vaccine targets. Recently, we have described immunological characterization of some of these P.vivax proteins and reported that they were highly immunogenic in humans [10], [11], [12], [13], [14]. The tryptophan-rich domains of all these proteins were also conserved in the parasite population.…”

Section: Introductionmentioning

confidence: 99%

Plasmodium vivax Tryptophan-Rich Antigen PvTRAg33.5 Contains Alpha Helical Structure and Multidomain Architecture

et al. 2011

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Tryptophan-rich proteins from several malarial parasites have been identified where they play an important role in host-parasite interaction. Structural characterization of these proteins is needed to develop them as therapeutic targets. Here, we describe a novel Plasmodium vivax tryptophan-rich protein named PvTRAg33.5. It is expressed by blood stage(s) of the parasite and its gene contains two exons. The exon 1 encodes for a 23 amino acids long putative signal peptide which is likely to be cleaved off whereas the exon 2 encodes for the mature protein of 252 amino acids. The mature protein contains B-cell epitopes which were recognized by the human immune system during P.vivax infection. The PvTRAg33.5 contains 24 (9.5%) tryptophan residues and six motifs whose patterns were similar among tryptophan-rich proteins. The modeled structure of the PvTRAg33.5 consists of a multidomain architecture which is stabilized by the presence of large number of tryptophan residues. The recombinant PvTRAg33.5 showed predominantly α helical structure and alpha helix to beta sheet transition at pH below 4.5. Protein acquires an irreversible non-native state at temperature more than 50°C at neutral pH. Its secondary and tertiary structures remain stable in the presence of 35% alcohol but these structures are destabilized at higher alcohol concentrations due to the disturbance of hydrophobic interactions between tryptophanyl residues. These structural changes in the protein might occur during its translocation to interact with other proteins at its final destination for biological function such as erythrocyte invasion.

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Cellular immune responses to recombinant Plasmodium vivax tryptophan‐rich antigen (PvTRAg) among individuals exposed to vivax malaria

Cited by 13 publications

References 30 publications

Erythrocyte Binding Activity Displayed by a Selective Group of Plasmodium vivax Tryptophan Rich Antigens Is Inhibited by Patients’ Antibodies

Erythrocyte Binding Activity Displayed by a Selective Group of Plasmodium vivax Tryptophan Rich Antigens Is Inhibited by Patients’ Antibodies

Host–parasite interaction: multiple sites in the Plasmodium vivax tryptophan‐rich antigen PvTRAg38 interact with the erythrocyte receptor band 3

Plasmodium vivax Tryptophan-Rich Antigen PvTRAg33.5 Contains Alpha Helical Structure and Multidomain Architecture

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