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Elicitation of specific cytotoxic T cells by immunization with malaria soluble synthetic polypeptides.
Journal of Immunology
We have studied the immunogenicity of Plasmodium falciparum circumsporozoite (CS) protein-derived synthetic polypeptides in mice. These synthetic peptides correspond to the N- and the C-terminal domains 22-125 and 289-390, respectively of the P. falciparum 7G8 isolate CS protein expressed on the sporozoite surface. They comprise what is believed to be the mature protein, except for the central repetitive B cell domain. BALB/c (H-2d) mice were immunized s.c. with 50 micrograms soluble CS polypeptides emulsified in IFA. After a single immunization, CS-specific helper and cytotoxic T lymphocytes (CTLs) could be obtained. The resultant CTLs obtained by in vitro restimulation of primed lymph node (LN) cells recognized H-2Kd target cells in the presence of short synthetic peptides defined in the present study. These epitopes are contained within the N- and C-terminal regions of the CS protein, and correspond to sequences 39-47 and 333-342. In addition, these CTLs can specifically lyse H-2d target cells transfected with the CS gene. These results suggest that, by immunization of mice with large soluble CS synthetic polypeptides in IFA, it is possible to obtain MHC class I-restricted T cell responses specific for the CS protein. This approach might be advantageous in the formulation of efficient malaria subunit vaccines.
Amino Acid Sequence, Animals, H-2 Antigens/immunology, Malaria Vaccines/immunology, Mice, Mice, Inbred BALB C, Molecular Sequence Data, Peptide Fragments/biosynthesis, Peptide Fragments/immunology, Protozoan Proteins/biosynthesis, Protozoan Proteins/immunology, Recombinant Proteins/biosynthesis, T-Lymphocytes, Cytotoxic/immunology, Transfection
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