T-CELL RECOGNITION OF A POINT MUTATION IN THE P21 RAS PROTEIN

Point mutations of p21 Ras proteins correlate with many human malignan cies. To determine whether the mutations of Ras proteins generate immu nogenic , determinants which can be recognized by T cells and possibly serve as targets for immunotherapy, we studied the murine T helper re sponses to synthetic Ras peptides corresponding to amino acids 1-23 of normal or mutant Ras protein. Immunization of C3H/He and BIO.BR mice with Ras peptides containing a valine mutation at position 12 stimulat ed MHC class II-restricted T helper cells which recognised specificall y the Ras mutation. Surprisingly C57BL/10 mice generated T helper resp onses not only against mutant but also against normal Ras peptides. Im portantly, natural processing of Ras protein was found to generate the epitopes recognized by the peptide-induced T cells.