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

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.