title: HLA-A*0201 restricted CD8+ T-lymphocyte responses to malaria: identification of new Plasmodium falciparum epitopes by IFN-gamma ELISPOT.
abstract: The role of antigen specific CD8+ T-lymphocytes in mediating protection against sporozoite-induced malaria has been well established in murine models. In humans, indirect evidence has accumulated suggesting a similar protective role for antigen-specific CD8+ T-lymphocytes. Nevertheless, the low frequency of circulating specific cells together with the lack of sensitive methods to quantify them has hampered the direct assessment of their function. Using a combination of short-term cell culture and IFN-gamma ELISPOT, we studied CD8+ T-lymphocyte responses to a panel of HLA-A*0201 binding peptides. In addition to confirming the response to already described epitopes, we also identified five new CD8+ T-lymphocyte epitopes. These epitopes are presented in pre-erythrocytic stages gene products of Plasmodium falciparum 7G8 strain and correspond to the following protein segments: circumsporozoite (CS) 64-72, 104-113, 299-308 and 403-411; liver stage antigen (LSA-1) repeat region; sporozoite surface protein 2 or thrombospondin related anonymous protein (SSP2/TRAP) 78-88 and 504-513. Four of these peptides are conserved amongst all published sequences of P. falciparum strains. We conclude that the modified IFN-gamma ELISPOT assay is a sensitive technique to monitor antigen-specific CD8+ T-lymphocyte responses in human malaria which may help in the improvement and assessment of the efficacy of malaria subunit vaccines.
authors.affiliation: Instituto de Inmunología del Valle, Universidad del Valle, Cali, Colombia.
authors.forename: J M
authors.initials: JM
authors.lastname: González
authors.forename: K
authors.initials: K
authors.lastname: Peter
authors.forename: F
authors.initials: F
authors.lastname: Esposito
authors.forename: I
authors.initials: I
authors.lastname: Nebié
authors.forename: J M
authors.initials: JM
authors.lastname: Tiercy
authors.forename: A
authors.initials: A
authors.lastname: Bonelo
authors.forename: M
authors.initials: M
authors.lastname: Arévalo-Herrera
authors.forename: D
authors.initials: D
authors.lastname: Valmori
authors.forename: P
authors.initials: P
authors.lastname: Romero
authors.forename: S
authors.initials: S
authors.lastname: Herrera
authors.forename: G
authors.initials: G
authors.lastname: Corradin
authors.forename: J A
authors.initials: JA
authors.lastname: López
mesh_terms: D000328:Adult; D000818:Animals; D000953:Antigens, Protozoan / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D018604:Epitope Mapping; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005260:Female; D015789:HLA-A2 Antigen / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology*; D016778:Malaria, Falciparum / Q000276:immunology*; D008297:Male; D010455:Peptides / Q000276:immunology; D010963:Plasmodium falciparum / Q000276:immunology
chemical_list: D000953:Antigens, Protozoan; D018984:Epitopes, T-Lymphocyte; D015789:HLA-A2 Antigen; D010455:Peptides; D007371:Interferon-gamma