The 3' portion of the gene for a Plasmodium yoelii merozoite surface antigen encodes the epitope recognized by a protective monoclonal antibody.
The 230-kDa merozoite antigen of the murine malarial parasite Plasmodium yoelii provides a potential model system for the development of a protective erythrocytic stage vaccine. To characterize this antigen at the molecular level, isolated P. yoelii 17XL DNA was used to construct a genomic library in the expression vector lambda gt11. A monoclonal antibody, mAb 302, which passively protected mice against P. yoelii challenge infection, was used to identify a lambda gt11 recombinant clone encoding a portion of the 230-kDa antigen of this parasite. Using this clone as a probe, we identified an mRNA of 7.6 kilobases by RNA blot analysis. Nucleic acid sequence analysis of the clone showed that the epitope recognized by the protective mAb 302 is encoded by the 3' portion of the gene for the 230-kDa antigen. The deduced amino acid sequence revealed that this antigen also contains the tandemly repeated tetrapeptide Gly-Ala-Val-Pro, a series of 10 cysteine residues located within the terminal 110 amino acids, and a potential membrane anchor of 18 hydrophobic residues. Comparison of this C-terminal sequence with the carboxyl segment of the 195-kDa merozoite antigen of Plasmodium falciparum revealed nucleic acid and amino acid sequence similarities ranging from 40% to 70%. The localization of a B-cell epitope recognized by the protective mAb 302 to this carboxyl region of the P. yoelii antigen, combined with the limited strain variability in this region of the homologous 195-kDa antigen of P. falciparum, has implications for the development of an effective erythrocytic stage malarial vaccine.
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal; D000953:Antigens, Protozoan / Q000235:genetics*; D000954:Antigens, Surface / Q000235:genetics*; D001483:Base Sequence; D003001:Cloning, Molecular; D004262:DNA Restriction Enzymes; D000939:Epitopes / Q000032:analysis / Q000235:genetics*; D005796:Genes; D008288:Malaria / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D010967:Plasmodium yoelii / Q000235:genetics*; D012689:Sequence Homology, Nucleic Acid
D000911:Antibodies, Monoclonal; D000953:Antigens, Protozoan; D000954:Antigens, Surface; D000939:Epitopes; D004262:DNA Restriction Enzymes