Interaction between epithelial cells and T cells may initiate autoimmune tissue destruction. Renal tubular epitheliai cells may participate in such immune interactions since they:(1) can be induced to express surface molecules which facilitate engagement with T cells;(2) secrete and express membrane bound cytokines;(3) are exposed to peptides from blood and the glomerular filtrate and are capable of processing these potentially immunogenic peptides. We have recently established T cell clones captured from the interstitium of MRL-lpr mice with lupus nephritis. These T cell clones are unique and are regulated by the Ipr gene. They express the α/β T cell receptor, and β cell markers, but do not display CD4 or CD8 on their surface. These T cell clones proliferate to renal tubular cells but not lo cells from other tissues and secrete IFN-γ which induces class II and ICAM-1 on renal tubular epithelial cells. Expression of class II and ICAM-1 induced by IFN-γ renders these epithelial cells capable of triggering T cell hybridomas to proliferate and secrete IL-2. Therefore, renal tubular epithelial cells are capable of processing and presenting antigen. This review will focus on the dynamic interaction of renal epithelial cells and T cells and discuss its importance in the initiation of autoimmune renal injury.