Selective Antigen Presenting Activity of Cortical Thymic Epithelial Cells against CD4+T Cells Associated with both Lack of Costimulatory Molecules and Inefficient Presentation of MHC–Peptide Ligands

Selective activation among several effector functions of a T cell clone, DB14, specific for pigeon cytochromec43-58 (p43-58) and restricted to I-Ab/dwas induced by antigen (Ag) presentation with nonprofessional Ag-presenting cells (APC), cortical thymic epithelial cells (c-TEC) (B7-1−CD40−), whereas full activation of the DB14 was induced with another nonprofessional APC, I-AbL cell (B7-1+CD40+). In the present study, to elucidate the mechanism underlying the selective activation of DB14 cells by c-TEC, we established c-TEC transfected with human CD40 alone (huCD40-c-TEC) or both human CD40 and murine B7-1 (huCD40/mB7-1-c-TEC), and compared the APC functions with those of the original c-TEC and I-AbL cell. IFN-γ production but not the proliferative response of DB14 was elevated by Ag presentation with huCD40-c-TEC as compared with unmanipulated c-TEC. On the other hand, upon stimulation with Ag plus huCD40/mB7-1-c-TEC both a significant proliferative response and IFN-γ production were induced in DB14. However, the level of these responses did not reach that induced in the presence of I-AbL cell. A similar pattern of APC functions was demonstrated with the other B7-independent T cell clone, PAB3, or T cell hybridomas (DBhy22 and BD7-5) which are basically independent of costimulation for the activation. The present finding along with our previous report that several structural differences of I-Abmolecules are present between c-TEC and I-AbL cell suggests that the distinct APC activity of c-TEC is attributable not only to a lack of B7-1 and CD40 but also to inefficient presentation of MHC–peptide complex on the c-TEC.