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 II 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.
Moreno
A
A
Department of Medical and Molecular Parasitology, New York University School of Medicine, NY 10010.
Clavijo
P
P
Edelman
R
R
Davis
J
J
Sztein
M
M
Herrington
D
D
Nardin
E
E
D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002460:Cell Line / Q000276:immunology; D000939:Epitopes / Q000276:immunology*; D006801:Humans; D007114:Immunization; D016778:Malaria, Falciparum / Q000276:immunology; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis / Q000276:immunology; D010963:Plasmodium falciparum / Q000276:immunology*; D015800:Protozoan Proteins / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D000939:Epitopes; D010455:Peptides; D015800:Protozoan Proteins