Differences in immunological response to a T. gondii protein (SAG1) derived peptide between two strains of mice: effect on protection in T. gondii infection.
This study presents the analysis of the immunogenicity, antigenicity and protective effects of a peptide derived from the major surface antigen of Toxoplasma gondii, SAG1. This synthetic peptide carrying three predicted H-2k restricted T cell epitopes was used to immunize mice. The protective effect of the peptide was evaluated in CBA/J and C57BL/6 mice using the decrease in brain cyst load as evidence of protection. Immunization of C57BL/6 mice yielded high antibody titres but had no protective effect after oral challenge. Immunized CBA/J, mice which responded with a lower titre, showed a 35% reduction in cyst burden after oral challenge. Both strains yielded antibodies which recognized the cognate SAG1 protein on immunoblot assay. Using the BIAcore, system, it was shown that at lower titres the CBA/J mouse sera recognized the native SAG1 protein more effectively than the C57BL/6 mouse sera, yielding much higher anti-peptide titres. Lymphoproliferation assays using the peptide experimentally confirmed the predicted T-cell epitopes and showed that they were also recognized by cells of T. gondii infected mice. The anti-peptide subclass analysis suggested a Th1 orientation in CBA/J mice, whereas a Th2 orientation was observed in C57BL/6 mice. Finally, fine analysis of sequences recognized under MHC class I indicated the existence of a T-cell epitope in the H-2k haplotype (CBA/J mice) but not in the H-2b haplotype (C57BL/6 mice). This study provides a structural basis to the understanding of the vaccination response to one of the T. gondii antigens in different strains of mice.
Velge-Roussel
F
F
CJF INSERM 93-09 Immunologie des Maladies Infectieuses, Equipe associée INRA d'Immunologie Parasitaire, UFR des Sciences Pharmaceutiques, Tours, France. velge@univ-tours.fr
Moretto
M
M
Buzoni-Gatel
D
D
Dimier-Poisson
I
I
Ferrer
M
M
Hoebeke
J
J
Bout
D
D
D000818:Animals; D000953:Antigens, Protozoan / Q000276:immunology*; D000954:Antigens, Surface / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D006239:Haplotypes; D051379:Mice; D008810:Mice, Inbred C57BL / Q000276:immunology*; D008808:Mice, Inbred CBA / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology; D015800:Protozoan Proteins / Q000737:chemistry / Q000276:immunology*; D014122:Toxoplasma / Q000276:immunology*; D014611:Vaccination
D000953:Antigens, Protozoan; D000954:Antigens, Surface; D018984:Epitopes, T-Lymphocyte; D010446:Peptide Fragments; D015800:Protozoan Proteins; C047168:SAG1 antigen, Toxoplasma