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Many human tumor cells have been shown to express antigens that are recognized by autologous cytotoxic T lymphocytes (CTL) and the molecular nature of a number of melanoma antigens has been defined recently. Here we describe the characterization of an antigen recognized on a renal cell carcinoma by autologous CTL clones. This antigen is encoded by the HLA-A2 gene present in the tumor cells. The sequence of this gene differs from the HLA-A2 sequence found in autologous peripheral blood lymphocytes by a point mutation that results in an arginine to isoleucine exchange at residue 170, which is located on the alpha-helix of the alpha 2 domain. Transfection experiments with the normal and mutated HLA-A2 cDNA demonstrated that this amino acid replacement was responsible for the recognition of the HLA-A2 molecule expressed on the tumor cells. The mutant HLA-A2 gene was also detected in the original tumor tissue from the patient, excluding the possibility that the mutation had appeared in vitro. Thus, HLA class I molecules carrying a tumor-specific mutation can be involved in the recognition of tumor cells by autologous CTL.

Type

Journal article

Journal

J Exp Med

Publication Date

01/06/1996

Volume

183

Pages

2501 - 2508

Keywords

Aged, Amino Acid Sequence, Animals, Base Sequence, Carcinoma, Renal Cell, Cell Line, Cercopithecus aethiops, Cytotoxicity, Immunologic, DNA Primers, Gene Library, Genes, MHC Class I, HLA-A2 Antigen, Humans, Kidney Neoplasms, Models, Structural, Molecular Sequence Data, Point Mutation, Polymerase Chain Reaction, Protein Structure, Secondary, Recombinant Proteins, T-Lymphocytes, Cytotoxic, Transfection, Tumor Cells, Cultured, Tumor Necrosis Factor-alpha