title: 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.
authors.affiliation: Department of Virology and Immunology, Southwest Foundation for Biomedical Research, San Antonio, TX 78228.
authors.forename: R K
authors.initials: RK
authors.lastname: Bright
authors.forename: M H
authors.initials: MH
authors.lastname: Shearer
authors.forename: R C
authors.initials: RC
authors.lastname: Kennedy
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000276:immunology*; D015153:Blotting, Western; D002461:Cell Line, Transformed; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000276:immunology; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D030361:Papillomavirus Infections / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology; D013539:Simian virus 40 / Q000276:immunology*; D014412:Tumor Virus Infections / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000276:immunology*
chemical_list: D000952:Antigens, Polyomavirus Transforming; D000939:Epitopes; D010446:Peptide Fragments; D014614:Vaccines, Synthetic