title: Broadly distributed T cell reactivity, with no immunodominant loci, to the pre-erythrocytic antigen thrombospondin-related adhesive protein of Plasmodium falciparum in West Africans.
abstract: Protective immunity to malaria has been achieved in human volunteers utilizing the pre-erythrocytic Plasmodium falciparum antigen, the circumsporozoite protein (CS). However, T cell reactivity to CS is focused on several highly polymorphic T cell epitope regions, potentially limiting the efficacy of any vaccine to specific malaria strains. Another important pre-erythrocytic malaria antigen, the thrombospondin-related adhesive protein (TRAP), can induce protection in animal models of malaria, but knowledge of human T cell responses is limited to the identification of CD8 T cell epitopes, with no CD4 epitopes identified to date. This comprehensive study assessed reactivity to overlapping peptides spanning almost the whole of P. falciparum TRAP (PfTRAP), as well as peptides selected on the basis of HLA class II-binding motifs. A total of 50 naturally exposed Gambian adults were assessed to define 26 T cell epitopes in PfTRAP capable of inducing rapid IFN-gamma or IL-4 production, as assessed by enzyme-linked immunospot assays. In contrast to the CS protein, this reactivity was broadly distributed along the length of TRAP. Moreover, of the 26 epitopes identified, 10 were found to be conserved in West Africa.
authors.affiliation: Institute of Molecular Medicine, Nuffield Department of Medicine, John Radcliffe Hospital, Oxford, GB.
authors.forename: K L
authors.initials: KL
authors.lastname: Flanagan
authors.forename: M
authors.initials: M
authors.lastname: Plebanski
authors.forename: P
authors.initials: P
authors.lastname: Akinwunmi
authors.forename: E A
authors.initials: EA
authors.lastname: Lee
authors.forename: W H
authors.initials: WH
authors.lastname: Reece
authors.forename: K J
authors.initials: KJ
authors.lastname: Robson
authors.forename: A V
authors.initials: AV
authors.lastname: Hill
authors.forename: M
authors.initials: M
authors.lastname: Pinder
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D000953:Antigens, Protozoan / Q000235:genetics; D005260:Female; D005714:Gambia; D006684:HLA-DR Antigens / Q000378:metabolism; D059811:HLA-DRB1 Chains; D006801:Humans; D016056:Immunodominant Epitopes / Q000235:genetics; D007371:Interferon-gamma / Q000378:metabolism; D016778:Malaria, Falciparum / Q000276:immunology; D008297:Male; D008969:Molecular Sequence Data; D010963:Plasmodium falciparum / Q000235:genetics / Q000276:immunology*; D015800:Protozoan Proteins / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology
chemical_list: D000953:Antigens, Protozoan; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D016056:Immunodominant Epitopes; D015800:Protozoan Proteins; C069428:thrombospondin-related adhesive protein, protozoan; D007371:Interferon-gamma