SV40 LARGE TUMOR-ANTIGEN ASSOCIATED SYNTHETIC PEPTIDES DEFINE NATIVE ANTIGENIC DETERMINANTS AND INDUCE PROTECTIVE TUMOR-IMMUNITY IN MICE

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 six 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.