title: Localization of HLA-A2.1-restricted T cell epitopes in the circumsporozoite protein of Plasmodium falciparum.
abstract: Localization of human MHC class I-restricted T cell epitopes in the circumsporozoite (CS) protein of the human parasite Plasmodium falciparum is an important objective in the development of antimalarial vaccines. To this purpose, we synthesized a series of overlapping synthetic 20-mer peptides, spanning the entire sequence of the 7G8 CS molecule except for the central repeat B cell domain. The P.f.CS peptides were first tested for their ability to bind to the human MHC class I HLA-A2.1 molecule on T2, a human cell line. Subsequently, the use of a series of shorter peptide analogues allowed us to determine the optimal A2.1 binding sequence present in several of the 20-mers. Binding P.f.CS peptides were further tested for their capacity to activate PBL from HLA-A2.1+ immune donors living in a malaria-endemic area. Specific IFN-gamma production was detected in the supernatant of cultures of PBL from exposed individuals. Cytotoxic T cell lines and clones were derived from the PBL of one responder, and their activity was shown to be HLA-A2.1-restricted and specific for the peptide 334-342 of the CS protein. In addition, double transgenic HLA-A2.1 x human beta 2-microglobulin mice were immunized with peptide 1-10 of the CS protein. T cells derived from immune lymph nodes displayed a peptide-specific HLA-A2.1-restricted cytolytic activity after one in vitro stimulation.
authors.affiliation: Institute of Biochemistry, University of Lausanne, Epalinges, Switzerland.
authors.forename: U
authors.initials: U
authors.lastname: Blum-Tirouvanziam
authors.forename: C
authors.initials: C
authors.lastname: Servis
authors.forename: A
authors.initials: A
authors.lastname: Habluetzel
authors.forename: D
authors.initials: D
authors.lastname: Valmori
authors.forename: Y
authors.initials: Y
authors.lastname: Men
authors.forename: F
authors.initials: F
authors.lastname: Esposito
authors.forename: L
authors.initials: L
authors.lastname: Del Nero
authors.forename: N
authors.initials: N
authors.lastname: Holmes
authors.forename: N
authors.initials: N
authors.lastname: Fasel
authors.forename: G
authors.initials: G
authors.lastname: Corradin
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D003602:Cytotoxicity, Immunologic; D018604:Epitope Mapping; D000939:Epitopes; D015789:HLA-A2 Antigen / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular; D007371:Interferon-gamma / Q000096:biosynthesis; D008213:Lymphocyte Activation; D016778:Malaria, Falciparum / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D010963:Plasmodium falciparum / Q000276:immunology*; D011485:Protein Binding; D015800:Protozoan Proteins / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D000939:Epitopes; D015789:HLA-A2 Antigen; D010455:Peptides; D015800:Protozoan Proteins; C041595:circumsporozoite protein, Protozoan; D007371:Interferon-gamma