title: Cytotoxic T lymphocyte (CTL) low-responsiveness to the Plasmodium falciparum circumsporozoite protein in naturally-exposed endemic populations: analysis of human CTL response to most known variants.
abstract: Cytotoxic T lymphocytes (CTL) specific for epitope(s) within the circumsporozoite (CS) protein of malaria sporozoites have been shown to play an important role in protective immunity against malaria, at least in murine models. Their role in sporozoite immunity in the human host has, however, not yet been elucidated. Immunological non-responsiveness and antigenic diversity within T cell epitopes of the CS protein have been identified as potential problems in producing a sporozoite vaccine. These factors may contribute to the widespread lack of sporozoite immunity in endemic populations. In this study, 137 individuals with a history of natural endemic exposure to falciparum sporozoites (119 resident in north west Thailand and 18 resident in coastal Papua New Guinea) were tested for a CTL response to the Plasmodium falciparum CS protein. Fifty-four overlapping peptides, spanning the entire sequence of the CS protein of P. falciparum including most known variants, were studied. While most individuals had antibodies to the immunodominant B cell repeat, (NANP)n, and while CTL specific for an influenza virus matrix synthetic peptide could be generated from five of 23 Karen Thai individuals tested, no CS protein-specific CTL could be detected in these populations. Our data have important implications for vaccine programs.
authors.affiliation: Molecular Immunology Unit, Queensland Institute of Medical Research, Bancroft Centre, Brisbane, Australia.
authors.forename: D L
authors.initials: DL
authors.lastname: Doolan
authors.forename: C
authors.initials: C
authors.lastname: Khamboonruang
authors.forename: H P
authors.initials: HP
authors.lastname: Beck
authors.forename: R A
authors.initials: RA
authors.lastname: Houghten
authors.forename: M F
authors.initials: MF
authors.lastname: Good
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000595:Amino Acid Sequence; D000818:Animals; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000276:immunology; D005260:Female; D006801:Humans; D007108:Immune Tolerance; D007111:Immunity, Cellular; D066298:In Vitro Techniques; D008213:Lymphocyte Activation / Q000276:immunology; D008288:Malaria / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D010219:Papua New Guinea; D010446:Peptide Fragments / Q000276:immunology; D010963:Plasmodium falciparum / Q000276:immunology*; D015800:Protozoan Proteins / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D013785:Thailand
chemical_list: D000939:Epitopes; D010446:Peptide Fragments; D015800:Protozoan Proteins; C041595:circumsporozoite protein, Protozoan