A MUTATED HLA-A2 MOLECULE RECOGNIZED BY AUTOLOGOUS CYTOTOXIC T-LYMPHOCYTES ON A HUMAN RENAL-CELL CARCINOMA

Many human tumor cells have been shown to express antigens that are re cognized by autologous cytotoxic T lymphocytes (CTL) and the molecular nature of a number of melanoma antigens has been defined recently. He re we describe the characterization of an antigen recognized on a rena l 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 isoleuc ine exchange at residue 170, which is located on the alpha-helix of th e alpha 2 domain. Transfection experiments with the normal and mutated HLA-A2 cDNA demonstrated that this amino acid replacement was respons ible 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-sp ecific mutation can be involved in the recognition of tumor cells by a utologous CTL.