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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.

Original publication

DOI

10.1002/(SICI)1521-4141(199906)29:06<1943::AID-IMMU1943>3.0.CO;2-1

Type

Journal article

Journal

Eur J Immunol

Publication Date

06/1999

Volume

29

Pages

1943 - 1954

Keywords

Adult, Amino Acid Sequence, Animals, Antigens, Protozoan, Female, Gambia, HLA-DR Antigens, HLA-DRB1 Chains, Humans, Immunodominant Epitopes, Interferon-gamma, Malaria, Falciparum, Male, Molecular Sequence Data, Plasmodium falciparum, Protozoan Proteins, T-Lymphocytes, Th2 Cells