Dendritic cells (DCs) have been used as professional antigen-presenting cells in vitro to prime T-cell responses. In this study, we generated both CD8+ and CD4+ renal cell carcinoma (RCC)-reactive T cells using a completely autologous system of DCs presenting engulfed whole-tumor cells. We compared DCs presenting RCC tumor cells in different preparations and found ultraviolet-irradiated apoptotic tumor cells to be more immunogenic than necrotic tumor cells or live untreated tumor cells in generating tumor-reactive T cells. In analyzing the T cells generated in this fashion, a CD8+ RCC-reactive T-cell clone generated from a patient recognized an epitope derived from fibroblast growth factor 5 in the context of human leukocyte antigen (HLA) B44*02. CD4+ T cells generated from another patient recognized multiple allogeneic RCC lines expressing HLA-DRbeta1*04, indicating a common shared tumor antigen presented by HLA-DRbeta1*04. The technique of using DCs to present whole-tumor cells can consistently generate both CD4+ and CD8+ RCC-reactive T cells for use in both antigen identification and therapeutic protocols.