An Ovalbumin Peptide-Specific Cytotoxic T Cell Clone with Antigen Self-Presentation Capacity Uses Two Distinct Mechanisms to Kill Target Cells

Cloned 10BK.1 T cells with specificity for the ovalbumin peptide OVA257-264 are representative of a novel cell type within the CD8+ subset of T cells. In the presence and in the absence of added antigen presenting cells these T cells react toward antigen (Ag) by proliferation and lymphokine production. These data suggest self-presentation of the Ag by 10BK.1 cells. Here we present evidence that 10BK.1 cells exhibit cytotoxic activity that involves two different cytotoxic effector mechanisms. (i) One mechanism is fast killing activity, apparent within 4 hr. Constitutive mouse T cell-specific proteinase-1 (MTSP-1) activity, constitutive expression of MTSP-1 RNA, increased by Ag challenge, and Ag-inducible perforin RNA expression were observed. Electron microscopic dense granules of the CTL were oriented toward Ag-pulsed target cells. The fast form of cytotoxicity was triggered by Ag recognition and by contact with IL-2. (ii) The other mechanism is slow cytolytic activity, manifested within 2 days. This activity was contained in the supernatant of 10BK.1 cells after Ag activation. It was inhibited by monoclonal anti-TNF antibodies and therefore presumably represents TNFα/β. Cytotoxic T cells capable of antigen self-presentation may be responsible for tissue damage during bacterial and viral infections.