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.
BACKGROUND
Plasmodium 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.


METHODS
We 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 CIDRalpha, CIDRbeta and DBLbeta-delta domains, DBLalpha 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.


RESULTS
All 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 DBLalpha and EXON 2 in the malaria-exposed donors living in Benin than in the UK malaria-unexposed donors.


CONCLUSIONS
These 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.
Sanni
Latifu A
LA
Division of Parasitology, National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK. lsanni@nimr.mrc.ac.uk
Allsopp
Catherine E M
CE
Reubsaet
Lieke
L
Sanni
Ambaliou
A
Newbold
Chris
C
Chauhan
Virander S
VS
Langhorne
Jean
J
D000293:Adolescent; D000328:Adult; D000349:Africa; D000818:Animals; D000953:Antigens, Protozoan / Q000276:immunology*; D001541:Benin; D015704:CD4 Antigens / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000502:physiology; D002455:Cell Division / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D017124:Conserved Sequence / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D005260:Female; D006801:Humans; D008297:Male; D010455:Peptides / Q000276:immunology; D010963:Plasmodium falciparum / Q000737:chemistry* / Q000276:immunology; D015800:Protozoan Proteins / Q000276:immunology*
D000953:Antigens, Protozoan; D015704:CD4 Antigens; D016207:Cytokines; D010455:Peptides; D015800:Protozoan Proteins; C085731:erythrocyte membrane protein 1, Plasmodium falciparum