CYTOTOXIC CD4+ T-CELLS FROM A SPOROZOITE-IMMUNIZED VOLUNTEER RECOGNIZE THE PLASMODIUM-FALCIPARUM CS PROTEIN

The present data provide the first evidence that a protozoan parasite, Plasmodium falciparum, can induce CD4+ cytotoxic T cells in man. The CD4+ cytotoxic T lymphocytes (CTL) were derived from a sporozoite-immunized volunteer who was protected against challenge with P. falciparum sporozoites. These T cells recognize an epitope within the circumsporozoite (CS) protein, an immunodominant sporozoite surface antigen, present also in liver stages of the parasite, which has been investigated as a vaccine candidate. The class I restricted T cell clones specifically lyse autologous B cells pulsed with a synthetic peptide representing a C-terminal sequence of the P. falciparum CS protein. The same peptide, as well as recombinant or native CS protein, also stimulates proliferation and gamma-interferon production by the CD4+ CTL. The CTL epitope, KIQNSLSTEW, is recognized in the context of HLA-DR7 and overlaps both a highly conserved, as well as a polymorphic, region of the P. falciparum CS protein.