title: 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.
abstract: AMA-1 of Plasmodium falciparum is a promising candidate antigen in malaria vaccine development. In this study, we have mapped the immunodominant T-cell determinants in this antigen by using synthetic peptides. From the amphipathic scores, 17 putative T-cell determinants were identified. Nine of the 17 peptides complementary to the putative T-cell determinants induced proliferation of peripheral blood mononuclear cells (PBMC) from Kenyan residents who had lifelong exposure to malaria; none of these peptides induced proliferation of PBMC from donors who were not previously exposed to malaria. This indicates that AMA-1 peptides were stimulating T cells that were previously primed by prior exposure to P. falciparum. Many positive responders showed reactivity to more than one peptide, and some of the potent proliferative T epitopes were found to be localized in the highly conserved regions of AMA-1, suggesting that it may be possible to induce T-cell memory that can recognize different variant forms of the parasite. This information on the natural immune responses against the AMA-1 vaccine antigen in clinically immune adults will be helpful in the development of an AMA-1 antigen-based malaria vaccine and may also guide testing of AMA-1-based vaccine formulations.
authors.affiliation: Division of Parasitic Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Public Health Service, U. S. Department of Health and Human Services, Atlanta, Georgia 30341-3717, USA
authors.forename: A A
authors.initials: AA
authors.lastname: Lal
authors.forename: M A
authors.initials: MA
authors.lastname: Hughes
authors.forename: D A
authors.initials: DA
authors.lastname: Oliveira
authors.forename: C
authors.initials: C
authors.lastname: Nelson
authors.forename: P B
authors.initials: PB
authors.lastname: Bloland
authors.forename: A J
authors.initials: AJ
authors.lastname: Oloo
authors.forename: W E
authors.initials: WE
authors.lastname: Hawley
authors.forename: A W
authors.initials: AW
authors.lastname: Hightower
authors.forename: B L
authors.initials: BL
authors.lastname: Nahlen
authors.forename: V
authors.initials: V
authors.lastname: Udhayakumar
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D000953:Antigens, Protozoan / Q000276:immunology*; D000939:Epitopes; D006801:Humans; D007113:Immunity, Innate; D008213:Lymphocyte Activation; D008288:Malaria / Q000276:immunology*; D017780:Malaria Vaccines / Q000276:immunology; D008565:Membrane Proteins / Q000276:immunology*; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology; D010963:Plasmodium falciparum / Q000276:immunology*; D015800:Protozoan Proteins / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D000953:Antigens, Protozoan; D000939:Epitopes; D017780:Malaria Vaccines; D008565:Membrane Proteins; D010446:Peptide Fragments; D015800:Protozoan Proteins; C090077:apical membrane antigen I, Plasmodium