ELICITATION OF SPECIFIC CYTOTOXIC T-CELLS BY IMMUNIZATION WITH MALARIA SOLUBLE SYNTHETIC POLYPEPTIDES

We have studied the immunogenicity of Plasmodium falciparum circumspor ozoite (CS) protein-derived synthetic polypeptides in mice. These synt hetic 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 domai n. BALB/c (H-2(d)) mice were immunized s.c. with 50 mu g soluble CS po lypeptides emulsified in IFA. After a single immunization, CS-specific helper and cytotoxic T lymphocytes (CTLs) could be obtained. The resu ltant CTLs obtained by in vitro restimulation of primed lymph node (LN ) cells recognized H-2K(d) target cells in the presence of short synth etic peptides defined in the present study. These epitopes are contain ed within the N- and C-terminal regions of the CS protein, and corresp ond to sequences 39-47 and 333-342. In addition, these CTLs can specif ically lyse H-2(d) target cells transfected with the CS gene. These re sults suggest that, by immunization of mice with large soluble CS synt hetic polypeptides in IFA, it is possible to obtain MHC class I-restri cted T cell responses specific for the CS protein. This approach might be advantageous in the formulation of efficient malaria subunit vacci nes.