Modifications of an immunodominant peptide antigen induce different anti-polyoma tumor responses in two separate mouse strains.

Abstract

An immunodominant polyoma peptide antigen MT162-176 was modified with regard to amino acid (aa) composition in an attempt to analyze its immunogenicity in detail. Twelve modifications of peptide MT162-176, 3 overlapping peptides and 9 peptides with point mutations, were synthesized and used for immunizations of (A.CA x C57BL/6)F1 and CBA mice against the syngeneic polyoma tumors SECA and SEBA. All 3 overlapping peptides MT162-176, MT165-174 and MT170-176, were immunogenic in (A.CA x C57BL/6)F1 mice against SECA, indicating that possibly more than one immunogenic epitope may be recognized within the MT162-176 sequence. In CBA mice, the 2 peptides covering the C-terminal half were immunogenic against SEBA, while the N-terminal peptide was possibly somewhat less efficient. The peptides with aa point mutations induced different anti-tumor responses in the 2 mouse strains. In CBA mice, only one mutant, MT162-176.28, was immunogenic. For (A.CA x C57BI)F1 3 different mutants, MT162-176.29, MT162-176.35 and MT162-176.36 were immunogenic against SECA, while the remaining 6 had lost their activity. These results suggest that a different emphasis of recognition of peptide MT162-176 exists with regard to the 2 mouse strains examined. Furthermore, different immunization procedures were tested. We found that repeated immunizations with peptide without Freund's adjuvant was the most efficient.