CELLULAR IMMUNE-RESPONSE TO HUMAN RENAL-CELL CARCINOMAS - DEFINITION OF A COMMON ANTIGEN RECOGNIZED BY HLA-A2-RESTRICTED CYTOTOXIC T-LYMPHOCYTE (CTL) CLONES

Cytotoxic T lymphocyte (CTL) clones directed against autologous renal- cell carcinoma (RCC) cell lines were generated by mixed lymphocyte/tum or-cell culture (MLTC) using peripheral blood lymphocytes (PBL). A CD8 (+), CD4(-) CTL clone MZ1257-CTL 5/30 with high cytolytic activity for the autologous tumor cell line MZ1257-RCC was established. No lysis o f the autologous EBV-transformed B lymphocytes (EBV-B) or K562 cells w as observed. A panel of HLA-A2-matched allogeneic RCC lines was recogn ized by CTL 5/30. Further specificity analysis showed a cross-reactivi ty with HLA-A2-matched allogeneic tumor cells of various origins, espe cially melanoma CTL 5/30 was also cross-reactive with several HLA-A2-p ositive allogeneic normal kidney cells in culture. The restriction ele ment identified for CTL 5/30 was HLA-A2, as shown by blocking of cytot oxicity using an anti-HLA-A2: monoclonal antibody (MAb) and by resista nce of an HLA-A2-negative melanoma variant SK29-MEL. 1.22 against lysi s by CTL 5/30. In this report we demonstrate HLA-A2-restricted recogni tion of a T-cell-defined antigen on autologous renal-cancer cells. Thi s antigen is also expressed and recognized in association with HLA-A2 on normal kidney cells in culture and other HLA-A2-positive tumor cell s. It may therefore be a normal differentiation antigen to which toler ance is incomplete in the renal-cell cancer system investigated. (C) 1 994 Wiley-Liss, Inc.