T cell recognition of a point mutation in the P21 Ras protein

Point mutations of p21 Ras proteins correlate with many human malignancies. To determine whether the mutations of Ras proteins generate immunogenic determinants which can be recognized by T cells and possibly serve as targets for immunotherapy, we studied the murine T helper responses to synthetic Ras peptides corresponding to amino acids 1-23 of normal or mutant Ras protein. Immunization of C3H/He and B10.BR mice with Ras peptides containing a valine mutation at position 12 stimulated MHC class II-restricted T helper cells which recognised specifically the Ras mutation. Surprisingly C57BL/10 mice generated T helper responses not only against mutant but also against normal Ras peptides. Importantly, natural processing of Ras protein was found to generate the epitopes recognized by the peptide-induced T cells.