DIFFERENCES IN IMMUNOLOGICAL RESPONSE TO A TOXOPLASMA-GONDII PROTEIN (SAG1) DERIVED PEPTIDE BETWEEN 2 STRAINS OF MICE - EFFECT ON PROTECTION IN TOXOPLASMA-GONDII INFECTION

This study presents the analysis of the immunogenicity, antigenicity a nd protective effects of a peptide derived from the major surface anti gen of Toxoplasma gondii, SAG1. This synthetic peptide carrying three predicted H-2(k) 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 protectio n. Immunization of C57BL/6 mice yielded high antibody titres but had n o protective effect after oral challenge. Immunized CBA/J, mice which responded with a lower titre, showed a 35% reduction in cyst burden af ter oral challenge. Both strains yielded antibodies which recognized t he cognate SAG1 protein on immunoblot assay. Using the BIAcore, system , it was shown that at lower titres the CBA/J mouse sera recognized th e native SAG1 protein more effectively than the C57BL/6 mouse sera, yi elding much higher anti-peptide titres. Lymphoproliferation assays usi ng the peptide experimentally confirmed the predicted T-cell epitopes and showed that they were also recognized by cells of T. gondii infect ed mice. The anti-peptide subclass analysis suggested a Th1 orientatio n in CBA/J mice, whereas a Th2 orientation was observed in C57BL/6 mic e. Finally, fine analysis of sequences recognized under MHC class I in dicated the existence of a T-cell epitope in the H-2(k) haplotype (CBA /J mice) but not in the H-2(b) haplotype (C57BL/6 mice). This study pr ovides a structural basis to the understanding of the vaccination resp onse to one of the T. gondii antigens in different strains of mice. (C ) 1998 Elsevier Science Ltd. All rights reserved.