CD8+ T-cell protective immunity induced by immunization with Plasmodium berghei CS protein-derived synthetic peptides: evidence that localization of peptide-specific CTLs is crucial for protection against malaria.
Immunization of BALB/c mice (H-2d) with a mixture of major histocompatibility complex (MHC) class I- and MHC class II-restricted synthetic peptides emulsified in incomplete Freund's adjuvant (IFA) induced a high level of specific cytotoxic T lymphocyte (CTL) activity. Peptides 249-260 or 252-260, derived from the circumsporozoite protein of Plasmodium berghei and representing a H-2Kd-restricted CTL epitope, were injected twice subcutaneously or intraperitoneally in BALB/c mice in combination with the tetanus toxin-derived universal T-helper peptide P30 in IFA. No protection was observed after exposure of immunized mice to infected mosquitoes. In contrast, when peptide 252-260-specific CTLs were expanded in vitro and adoptively transferred into naive recipient, mice were partially protected (64%) against a subsequent sporozoite challenge. Furthermore, direct transfer of lymph nodes or spleen cells from mice immunized with the peptide PbCS 252-260 also conferred protection to recipient mice. This protection was long-lasting and similar to that obtained with irradiated sporozoites.
Renggli
J
J
Institute of Biochemistry, University of Lausanne, Epalinges, Switzerland.
Valmori
D
D
Romero
J F
JF
Eberl
G
G
Romero
P
P
Betschart
B
B
Corradin
G
G
D000595:Amino Acid Sequence; D000818:Animals; D000939:Epitopes; D005260:Female; D007111:Immunity, Cellular; D008288:Malaria / Q000276:immunology / Q000517:prevention & control*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis / Q000276:immunology*; D010962:Plasmodium berghei / Q000276:immunology*; D015800:Protozoan Proteins / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D000939:Epitopes; D010455:Peptides; D015800:Protozoan Proteins; C041595:circumsporozoite protein, Protozoan