IDENTIFICATION OF T-CELL DETERMINANTS IN NATURAL IMMUNE-RESPONSES TO THE PLASMODIUM-FALCIPARUM APICAL MEMBRANE ANTIGEN (AMA-1) IN AN ADULT-POPULATION EXPOSED TO MALARIA
Aa. Lal et al., IDENTIFICATION OF T-CELL DETERMINANTS IN NATURAL IMMUNE-RESPONSES TO THE PLASMODIUM-FALCIPARUM APICAL MEMBRANE ANTIGEN (AMA-1) IN AN ADULT-POPULATION EXPOSED TO MALARIA, Infection and immunity, 64(3), 1996, pp. 1054-1059
AMA-1 of Plasmodium falciparum is a promising candidate antigen in mal
aria vaccine development. In this study, we have mapped the immunodomi
nant T-cell determinants in this antigen by using synthetic peptides.
From the amphipathic scores. 17 putative T-cell determinants were iden
tified, Nine of the 17 peptides complementary to the putative T-cell d
eterminants induced proliferation of peripheral blood mononuclear cell
s (PBMC) from Kenyan residents who had lifelong exposure to malaria; n
one of these peptides induced proliferation of PBMC from donors who we
re not previously exposed to malaria, This indicates that AMA-1 peptid
es were stimulating T cells that were previously primed by prior expos
ure to P. falciparum. Many positive responders showed reactivity to mo
re than one peptide, and some of the potent proliferative T epitopes w
ere found to be localized in the highly conserved regions of AMA-1. su
ggesting that it may be possible to induce T-cell memory that can reco
gnize different variant forms of the parasite, This information on the
natural immune responses against the AMA-1 vaccine antigen in clinica
lly immune adults will be helpful in the development of an AMA-1 antig
en-based malaria vaccine and may also guide testing of AMA-1-based vac
cine formulations.