title: The purine salvage enzyme hypoxanthine guanine xanthine phosphoribosyl transferase is a major target antigen for cell-mediated immunity to malaria.
abstract: Although there is good evidence that immunity to the blood stages of malaria parasites can be mediated by different effector components of the adaptive immune system, target antigens for a principal component, effector CD4(+) T cells, have never been defined. We generated CD4(+) T cell lines to fractions of native antigens from the blood stages of the rodent parasite, Plasmodium yoelii, and identified fraction-specific T cells that had a Th1 phenotype (producing IL-2, IFN-gamma, and tumor necrosis factor-alpha, but not IL-4, after antigenic stimulation). These T cells could inhibit parasite growth in recipient severe combined immunodeficient mice. N-terminal sequencing of the fraction showed identity with hypoxanthine guanine xanthine phosphoribosyl transferase (HGXPRT). Recombinant HGXPRT from the human malaria parasite, Plasmodium falciparum, activated the T cells in vitro, and immunization of normal mice with recombinant HGXPRT reduced parasite growth rates in all mice after challenge.
authors.affiliation: Cooperative Research Centre for Vaccine Technology, Queensland Institute of Medical Research, PO Royal Brisbane Hospital, Brisbane 4029, Australia.
authors.forename: Morris O
authors.initials: MO
authors.lastname: Makobongo
authors.forename: George
authors.initials: G
authors.lastname: Riding
authors.forename: Huji
authors.initials: H
authors.lastname: Xu
authors.forename: Chakrit
authors.initials: C
authors.lastname: Hirunpetcharat
authors.forename: Dianne
authors.initials: D
authors.lastname: Keough
authors.forename: John
authors.initials: J
authors.lastname: de Jersey
authors.forename: Peter
authors.initials: P
authors.lastname: Willadsen
authors.forename: Michael F
authors.initials: MF
authors.lastname: Good
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002455:Cell Division; D016207:Cytokines / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes; D005434:Flow Cytometry; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D007525:Isoelectric Focusing; D008213:Lymphocyte Activation; D008288:Malaria / Q000276:immunology* / Q000469:parasitology / Q000517:prevention & control*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D016513:Mice, SCID; D008969:Molecular Sequence Data; D010430:Pentosyltransferases / Q000737:chemistry* / Q000235:genetics; D010641:Phenotype; D010967:Plasmodium yoelii / Q000378:metabolism; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D018417:Th1 Cells; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D016207:Cytokines; D000939:Epitopes; D007376:Interleukin-2; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; D007371:Interferon-gamma; D010430:Pentosyltransferases; C083867:hypoxanthine-guanine-xanthine phosphoribosyltransferase