Cellular responses to Plasmodium falciparum erythrocyte membrane protein-1: use of relatively conserved synthetic peptide pools to determine CD4 T cell responses in malaria-exposed individuals in Benin, West Africa

Abstract

BackgroundPlasmodium falciparum erythrocyte membrane protein-1, a variant antigen of the malaria parasite, is potentially a target for the immune response. It would be important to determine whether there are CD4 T cells that recognise conserved regions. However, within the relatively conserved region, there is variation. It is not possible to test T cell responses from small field samples with all possible peptides.MethodsWe have aligned sequences that are relatively conserved between several PfEMP1 molecules, and chosen a representative sequence similar to most of the PfEMP1 variants. Using these peptides as pools representing CIDRα, CIDRβ and DBLβ-δ domains, DBLα domain, and EXON 2 domain of PfEMP1, we measured the CD4 T cell responses of malaria-exposed donors from Benin, West Africa by a FACS based assay.ResultsAll the three peptide pools elicited a CD4 T cell response in a proportion of malaria-exposed and non-exposed donors. CD4 T cell proliferation occurs at a relatively higher magnitude to peptide pools from the DBLα and EXON 2 in the malaria-exposed donors living in Benin than in the UK malaria-unexposed donors.ConclusionsThese findings suggest that an immunological recall response to conserved peptides of a variant antigen can be measured. Further testing of individual peptides in a positive pool will allow us to determine those conserved sequences recognised by many individuals. These types of assays may provide information on conserved peptides of PfEMP1 which could be useful for stimulating T cells to provide help to P. falciparum specific B cells.

Specific antibody responses against membrane proteins of erythrocytes infected by Plasmodium falciparum of individuals briefly exposed to malaria

“…Additionally, the passive transfer of IgG from highly exposed individuals (HEI) to non-immune patients could confer a protective effect to clinical symptoms of malaria [ 8 - 10 ]. Among proteins supposed to induce a protective immunity, the surface-expressed P. falciparum erythrocyte protein 1 (PfEMP-1) have been largely studied [ 11 - 13 ]. However, others erythrocytic parasite stage proteins were reported to elicit an immune response [ 14 - 17 ].…”

Prediction of B Cell and T Cell Epitopes of DBLα Domain in Plasmodium falciparum Malaria Vaccine Candidate Var Gene

“…It was suggested that the use of synthetic peptides representing conserved sequences of PfEMP1 might be of value in determining regions of the molecule recognised by T cells of a wide variety of donors exposed to different variants of PfEMP1 [9]. The synthetic peptide sequences overlapped in some extent to the sequences predicted by antigenic sites and B cell epitopes by us.…”

Plasmodium falciparum Variability and Immune Evasion Proceed from Antigenicity of Consensus Sequences from DBL6ε; Generalization to All DBL from VAR2CSA

“…The linear epitope carried by a synthetic peptide can induce antibodies that will protect mice against Semliki forest virus [55]. Some peptides have already been shown to be good immunogens [56], inducing strong T cell response. All these studies show that there is a real interest to design peptides as vaccine candidates.…”