The selective induction of effector functions of a T-cell clone (DB14), specific to pigeon cytochrome c 43-58 (p 43-58) and restricted to I-A^b, was analyzed using a professional antigen-presenting cell, B hybridoma (Th 2.58), and various non-professional antigen-presenting cells (APC), L cells transfected with I-A^b (I-A^b L cells), a medullary thymic epithelial cell line (m-TEC) and a cortical thymic epithelial cell line (c-TEC). The m-TEC and c-TEC expressed I-A^b upon induction with interferon γ (IFN-γ). When stimulated with p 43-58 in the presence of I-A^b L cells as well as Th 2.58 cells, the DB14 cells showed marked proliferation and, after 18hr of culturing, exhibited significant cytotoxicity against the APC. By contrast, in the presence of m, c-TEC, the DB14 cells showed neither proliferation nor cytotoxicity against these TEC but exhibited considerable detachment activity towards them. Furthermore, DB14 cells became expressed activation markers (CD69 or CD44) following stimulation with p 43-58 plus m-TEC or c-TEC. The addition of rIL-2 to the culture of DB14 cells, p 43-58 and m-TEC or c-TEC, restored the proliferative responses. However, it was shown that anergy was not involved in the negligible proliferative responses of DB14 cells after stimulation with p 43-58 plus m, c-TEC. The present findings indicate that differences in APC functions are present among non-professional APC and suggest that the selective induction of T-cell functions can be achieved using the appropriate non-professional APC. The characteristic activation of T cells by TEC may be related to their functional roles in situ.