Immunization In Vivo with the Oncogenic Protein

Many malignancies harbor mutated ras proto-oncogenes encoding 21 kDa proteins with single amino acid substitutions. Previous studies have shown that the aberrant p21 raJ proteins are potential tumor-specific antigens in that CD4'" class II major histocompatibIlity complex-restricted T cells spe· cific for the mutated segment of vanous oncogenic p21 raJ proteins can be elicited by immunization in vivo with synthetic peptides corresponding to the mutated segment. T·cell recognition of an antigenic peptide within a protein may be influenced substantially, either positively or negatively, by flanking amino acid sequences as well as by more distal immunogenic or toterogenic epitopes within the same protein. This study examined whether T cells specific for the mutated segment of an oncogenic p21 _aJ protein can be elicited by immunization in vivo with the protein. The results showed that p21raJ protein bearing the transforming single amino ac id substitution of leucine for glutamine at residue 61 could elicit T cells specifically reactive to the mutated region of the protein in C3HJHeN mice. Thus, an abnormal p21"JJ protein specifically associated with malignant transformation can be immunogenic in vivo. These results predict that in some circumstances. mutated pllraJ proteins expressed by malignancies might elicit detectable mutation-specific T-ceH responses.