SV40 large tumor antigen associated synthetic peptides define native antigenic determinants and induce protective tumor immunity in mice.

ABSTRACT

Synthetic peptides were utilized to define antigenic determinants on simian virus 40 (SV40) large tumor antigen (T-ag). Six synthetic peptides representing predicted B-cell epitopes on SV40 T-ag were used to immunize mice to compare the humoral immune responses and ascertain the ability of the peptide preparations to induce protective tumor immunity in vivo. Anti-peptide antibodies from BALB/c and C57BL/6 mice were examined for reactivity with SV40 T-ag by various immunologic assays. Antibodies from both strains to four of the peptides recognized recombinant SV40 T-ag by ELISA. However, T-ag recognition by anti-peptide antibodies differed when assessed by Western blot. Antibodies induced by the same four peptides in BALB/c mice recognized T-ag, whereas only three of the sex peptides induced antibodies in C57BL/6 mice capable of recognizing SV40 T-ag by Western blot. Flow cytometric analysis revealed that antibodies to peptides corresponding to T-ag amino acid residues 632-652 and 690-708 from BALB/c mice were able to recognize the surface of SV40 transformed cells, whereas five of the six peptides induced surface reactive antibodies in C57BL/6 mice. More important, peptides 632-652 and 690-708 elicited a protective immune response in BALB/c mice subsequently challenged with a lethal dose of syngeneic SV40 transformed cells. However, this tumor immunity was incomplete as only 50% of the mice survived the tumor challenge. These data indicate that antibodies induced by synthetic peptides corresponding to predicted B-cell epitopes on SV40 T-ag are capable of recognizing native and denatured determinants on T-ag. Furthermore, immune responses elicited by selected peptides partially protected BALB/c mice from a lethal tumor challenge.