A ras-Mutated Peptide Targeted by CTL Infiltrating a Human Melanoma Lesion

摘要: Ags derived from commonly mutated oncogenic proteins seem ideally suited as targets for tumor immunotherapy. Nonetheless, only a few epitopes efficiently presented by human tumors have thus far been identified. We describe here an approach to identify such epitopes. This involves: 1) identifying expressing ras mutation and isolating the tumor-infiltrating lymphocytes (TIL); 2) transfecting COS cells induce expression of unknown peptides in context patient's HLA class I molecules; 3) screening epitope recognition using TIL mutation. By this approach, there appeared be N-ras (a glutamine-to-arginine exchange at residue 61 (Q61R)), detected melanoma lesion, which was recognized specifically autologous HLA-A*0101 context. The peptide 55-64(Q61R) these regularly Q61R-mutated HLA-A*0101(+) cell lines. its wild-type homolog (55-64(wt)) bound with similar affinities. However, could specific CTL expansion PBL. All clones peptide, failed recognize sequence on both cells. These data show that protein mutations can create shared tumor-specific epitopes, cells, oncogene-transfected (from containing mutations) is powerful identification