Article: article from journal or magazin.
Localization of HLA-A2.1-restricted T cell epitopes in the circumsporozoite protein of Plasmodium falciparum.
Journal of Immunology
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.
Amino Acid Sequence, Animals, Cytotoxicity, Immunologic, Epitope Mapping, Epitopes, HLA-A2 Antigen/immunology, Humans, Immunity, Cellular, Interferon-gamma/biosynthesis, Lymphocyte Activation, Malaria, Falciparum/immunology, Mice, Mice, Transgenic, Molecular Sequence Data, Peptides/chemistry, Peptides/immunology, Plasmodium falciparum/immunology, Protein Binding, Protozoan Proteins/immunology, T-Lymphocytes/immunology
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