The molecular identification of antigens recognized by autologous cytotoxic T lymphocytes (CTL) on human tumors opens new possibilities of specific immunotherapy of cancer. Several antigens have recently been identified on human melanoma by a genetic approach. This project aims at identifying such antigens on renal cell carcinoma. A first requisite is the obtention of a CTL clone specifically directed against the autologous tumor line. To identify the antigen recognized by this CTL, a cDNA library from this tumor line will be transfered into COS cells, together with the cDNA encoding the presenting HLA molecule. Transfected COS cells will then be screened with the CTL by looking at their ability to induce TNF production by the CTL. This should allow the isolation of the cDNA encoding the antigen. This cDNA will then be sequenced and analysed by standard molecular biology techniques to define the pattern of expression of the tumor antigen and the nature of the antigenic peptide presented to the CTL.