CD4 ⁺ T Cell Response Correlates with Naturally Acquired Antibodies against Plasmodium vivax Tryptophan-Rich Antigens

Abstract

Tryptophan-rich proteins play important biological functions for the Plasmodium parasite. Plasmodium vivax contains remarkably large numbers of such proteins belonging to the "Pv-fam-a" family that need to be characterized. Earlier, we reported the presence of memory T cells and naturally acquired antibodies against 15 of these proteins in P. vivax malaria-exposed individuals (M. Zeeshan, H. Bora, and Y. D. Sharma, J Infect Dis 207:175-185, 2013, http://dx.doi.org/10.1093/infdis/jis650). Here, we sought to characterize and ascertain the cross talk between effector responses of T and B cells in malarial patients against all Pvfam-a family proteins. Therefore, we expressed the remaining 21 of these proteins in Escherichia coli and studied the humoral and cellular immune responses based on the same parameters used in our previous study. Naturally acquired IgG antibodies were detected against all 21 antigens in P. vivax patient sera (37.7 to 94.4% seropositivity). These antigens were able to activate the lymphocytes of P. vivax-exposed individuals, and the activated CD4 ؉ T lymphocytes produced higher levels of Th1 (interleukin-2 [IL-2] and gamma interferon [IFN-␥]) and Th2 (IL-4 and IL-10) cytokines than the healthy controls, but the response was Th2 biased. The combined results of present and previous studies seem to suggest a striking link between induction of the CD4 ؉ T cell response and naturally acquired antibodies against all 36 proteins of the Pv-fam-a family, the majority of them having conserved sequences in the parasite population. Further work is required to utilize this information to develop immunotherapeutic treatments for this disease. Despite continued efforts to control malaria, it remains a major health problem in affected tropical countries. There is an urgent need to develop an effective malaria vaccine and newer antimalarial drugs to control this disease. This requires the identification and characterization of newer parasite molecules that play significant biological function for the survival of the parasite and could generate cellular and humoral immune responses in humans to provide protection against the disease. Previous studies have shown that humoral and T-cell-mediated immune responses are induced against malaria parasite, and these responses were found to be antigen and stage specific (1). Antibodies come to play their role as soon as the parasite enters the human body. These antibodies not only clear the parasite by opsonization but also block the invasion of host cells by the parasite. Therefore, the humoral immune response plays a critical role in controlling the parasite.A role for dendritic cells, monocyte/macrophages, B cells, and several groups of T cells has been proposed in the cellular immune response against malaria (1-4). Some specific cytokines are produced from peripheral blood mononuclear cells in response to parasite infection, which further activates the host's macrophages, neutrophils, T cells, and natural killer cells to react against the parasites (5). Monocytes/ma...

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

“…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.…”

Basigin Interacts with Plasmodium vivax Tryptophan-rich Antigen PvTRAg38 as a Second Erythrocyte Receptor to Promote Parasite Growth

“…This is expected as these peptides were interacting with the host molecules for biological function, and any variation in parasite ligand in this region could be detrimental for host-parasite interaction. Furthermore, PvTRAg38 has been established as a potent immunogen (16). The presence of memory T cell against PvTRAg38 points toward the importance of this protein as immunogen, which can generate fast and specific immune response during P. vivax infection (17).…”

“…This recombinant DNA was then used to transfect the HEK-293 cells that were cultured in RPMI 1640 media with 10% fetal calf serum, 4 mM glutamine, 1ϫ penicillin/streptomycin, pH 7.4, in a humidified 5% CO 2 incubator at 37°C as described earlier (16). The transfection was done with cationic lipid Lipofectamine 2000, following the manufacturer's protocol.…”

Plasmodium vivax Tryptophan Rich Antigen PvTRAg36.6 Interacts with PvETRAMP and PvTRAg56.6 Interacts with PvMSP7 during Erythrocytic Stages of the Parasite

“…falciparum that encodes only five members [ 2 ]. Our group has been working on functional characterization of many of these proteins and has characterized their antigenicity in patient sera [ 10 , 28 ]. We have also illustrated that some of these proteins bind RBC and proposed that these may have a vaccine potential.…”

“…Previous studies have shown that PvTRAgs can induce the humoral as well as cellular immune responses during P . vivax infection and most of them exhibit sequence conservation [ 10 , 15 ]. Some of these PvTRAgs are also known to exhibit human erythrocyte binding activity which may be associated with rosetting or red cell invasion phenomenon [ 16 , 17 ].…”