RETROVIRAL TRANSDUCTION OF PROTEIN KINASE-C-GAMMA INTO CYTOTOXIC LYMPHOCYTE-T CLONES LEADS TO IMMORTALIZATION WITH RETENTION OF SPECIFIC FUNCTION

The molecular pathways that are responsible for delivering the proliferative signals from the cell surface to the nucleus in T lymphocytes are still unresolved, but recent data implicates protein kinase C (PKC) involvement in the TCR signaling pathway. To further address the role of PKC in T cell activation, the effects of high level expression of the PKC-gamma isoenzyme in murine CTL clones were examined. Unlike the parental cells that required periodic Ag stimulation for cell activation and growth, cells expressing a retrovirally transduced PKC-gamma gene propagated in culture independent of the need for Ag stimulation, although maintaining identical functional specificity to the parental CTL. Constituitive PKC-gamma expression may therefore mimic physiologic PKC activation, thereby abrogating the requirement for TCR-Ag interaction in T cell activation.