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A ras-Mutated Peptide Targeted by CTL Infiltrating a Human Melanoma Lesion 1

Abstract : Ags derived from commonly mutated oncogenic proteins seem ideally suited as targets for tumor immunotherapy. Nonetheless, only a few mutated epitopes efficiently presented by human tumors have thus far been identified. We describe here an approach to identify such epitopes. This approach involves: 1) identifying tumors expressing a ras mutation and isolating the tumor-infiltrating lymphocytes (TIL); 2) transfecting COS cells to induce expression of unknown mutated peptides in the context of a patient's HLA class I molecules; and 3) screening epitope recognition by using TIL from the tumors expressing a ras mutation. By using this approach, there appeared to be a N-ras mutation (a glutamine-to-arginine exchange at residue 61 (Q61R)), detected in a melanoma lesion, which was recognized specifically by the autologous TIL in the HLA-A*0101 context. The ras peptide 55-64 Q61R was the epitope of these TIL and was regularly presented by Q61R-mutated HLA-A*0101 ؉ melanoma cell lines. This peptide and its wild-type homolog (55-64 wt) bound to HLA-A*0101 with similar affinities. However, only the mutated peptide could induce specific CTL expansion from PBL. All the CTL clones specific to the mutated peptide, failed to recognize the wild-type sequence on both COS and melanoma cells. These data thus show that oncogenic protein mutations can create shared tumor-specific CTL epitopes, efficiently presented by tumor cells, and that screening for oncogene-transfected COS cell recognition by TIL (from tumors containing mutations) is a powerful approach for the identification of these epitopes.
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Contributor : Nathalie Labarriere <>
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Boris Linard, Stéphane Bézieau, Houssem Benlalam, Nathalie Labarrière, Yannick Guilloux, et al.. A ras-Mutated Peptide Targeted by CTL Infiltrating a Human Melanoma Lesion 1. Journal of Immunology, Publisher : Baltimore : Williams & Wilkins, c1950-. Latest Publisher : Bethesda, MD : American Association of Immunologists, 2002, 168 (9), pp.4802 - 4808. ⟨10.4049/jimmunol.168.9.4802⟩. ⟨inserm-02482150⟩

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