title: Analysis of human T cell clones specific for conserved peptide sequences within malaria proteins. Paucity of clones responsive to intact parasites.
abstract: T cells are thought to be of central importance in malaria immunity. Peptides copying malaria protein sequences often stimulate human CD4+ T cells and it was thought that they represented T cell epitopes present in the parasite and may thus have particular relevance to malaria vaccine development. To verify whether synthetic peptides representing highly conserved regions of parasite Ags may contribute to a malaria vaccine, we searched the data bank for conserved regions of Plasmodium falciparum malaria proteins that were not homologous to known self (human) proteins. We synthesized 24 such peptides representing 11 of the cloned and sequenced malaria asexual stage Ags, which were predicted by algorithms to represent T cell epitopes, and 6 peptides not predicted to be T cell epitopes and used these to generate T cell clones from individuals with an extensive previous history of malaria exposure. The T cell clones responded vigorously to many peptides but only a single clone, specific for a peptide within merozoite surface protein-1, 20-39, VTHESYQELVKKLEALEDAV, and not previously defined to be a T cell epitope responded to malaria parasites by proliferation and secretion of IFN-gamma. This epitope was not revealed by studying parasite-induced T cell lines and is thus subdominant. The clone was able to significantly inhibit parasite growth in vitro. The final step in the inhibition of parasite growth appears to be nonspecific because other activated clones (not specific for malaria sequences) can inhibit parasite growth. Our data suggest that few conserved peptides within malaria parasites can be processed from the intact parasite. However, such peptides that can be processed from malaria parasites may be expected to stimulate parasite-specific T cells that could inhibit parasite growth and as such may be lead candidates for a vaccine aimed at inducing cellular immunity to malaria.
authors.affiliation: Malaria and Arbovirus Unit, Queensland Institute of Medical Research, Brisbane, Australia.
authors.forename: I A
authors.initials: IA
authors.lastname: Quakyi
authors.forename: J
authors.initials: J
authors.lastname: Currier
authors.forename: A
authors.initials: A
authors.lastname: Fell
authors.forename: D W
authors.initials: DW
authors.lastname: Taylor
authors.forename: T
authors.initials: T
authors.lastname: Roberts
authors.forename: R A
authors.initials: RA
authors.lastname: Houghten
authors.forename: R D
authors.initials: RD
authors.lastname: England
authors.forename: J A
authors.initials: JA
authors.lastname: Berzofsky
authors.forename: L H
authors.initials: LH
authors.lastname: Miller
authors.forename: M F
authors.initials: MF
authors.lastname: Good
mesh_terms: D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D000818:Animals; D000953:Antigens, Protozoan / Q000737:chemistry / Q000276:immunology*; D002999:Clone Cells; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000276:immunology; D010963:Plasmodium falciparum / Q000276:immunology*; D015800:Protozoan Proteins / Q000737:chemistry / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D000953:Antigens, Protozoan; D010455:Peptides; D015800:Protozoan Proteins; D007371:Interferon-gamma