T helper epitopes enhance the cytotoxic response of mice immunized with MHC class I-restricted malaria peptides.
We have previously derived MHC class I (H-2Kd) restricted cytotoxic T lymphocytes (CTL) from BALB/c mice immunized with irradiated sporozoites from Plasmodium (P.) berghei and P. yoelii. The CTL recognize synthetic peptides corresponding to a region of the circumsporozoite (CS) protein that is homologous in the two species. In the present study, we have attempted to induce CS-specific CTL by immunization with those peptides in incomplete Freund's adjuvant. Only a low level CTL response was detected in BALB/c mice immunized with synthetic peptides corresponding to the Pb or Py CTL epitopes. In contrast, CS-specific CTL responses could be readily detected in mice injected with mixtures of peptides that combined the P. berghei or P. yoelii CTL epitopes with previously defined T helper epitopes. Several different T helper epitopes were shown to enhance the response when injected as separate peptides in a mixture, or when covalently linked to a CTL epitope. These results may have general implications for the elicitation of CTL responses to defined CTL epitopes and for the design of peptide-based synthetic vaccines.
Widmann
C
C
Institute of Biochemistry, University of Lausanne, Epalinges, Switzerland.
Romero
P
P
Maryanski
J L
JL
Corradin
G
G
Valmori
D
D
D000595:Amino Acid Sequence; D000818:Animals; D000953:Antigens, Protozoan / Q000276:immunology*; D000939:Epitopes / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D007114:Immunization; D008288:Malaria / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis / Q000276:immunology; D010962:Plasmodium berghei / Q000276:immunology; D010967:Plasmodium yoelii / Q000276:immunology; D015800:Protozoan Proteins / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
D000953:Antigens, Protozoan; D000939:Epitopes; D015395:Histocompatibility Antigens Class I; D010455:Peptides; D015800:Protozoan Proteins; C041595:circumsporozoite protein, Protozoan