Engagement of natural cytotoxicity programs regulates AP-1 expression in the NKL human NK cell line

NK cell cytotoxicity is a fast and efficient mechanism of target cell lysis , Using transcription analysis, such as multiples messenger assays, we show here that natural cytotoxicity exerted by the human NKL cell line correlat es with mRNA accumulation of very early activator protein (AP)-1 transcript ion factor genes such as JunB, FosB and c-Fos, In addition, DNA-binding act ivities of Jun-Fos heterodimers were observed by electrophoretic mobility s hift assays during the course of natural cytotoxicity. Interaction between immunoglobulin-like transcript-2/leukocyte Ig-like receptor I on NKL cells and HLA-B27 on target cells leads to an impairment of NKL natural cytotoxic ity, which correlates with an absence of JunB, FosB, end c-Fos transcriptio n, as well as an absence of their DNA-binding activity. Our studies thus in dicate that, despite the rapidity of NK cell-mediated lysis, AP-1 transcrip tion factor is activated during the early stage of Ir;I; cell cytolytic pro grams and that engagement of NK cell inhibitory receptors for MHC class I m olecules impairs the very early activation of AP-1.