Somatic mutagenesis studies of NF-κB signaling in human T cells:: evidence for an essential role of IKKγ in NF-κB activation by T-cell costimulatory signals and HTLV-I Tax protein

NF-kappa B plays a pivotal role in normal T-cell activation and may also mediate human T-cell leukemia virus (HTLV)-induced T-cell transformation. Activation of NF-kappa B by both T-cell costimulatory signals and the HTLV Tax protein involves stimulation of I kappa B kinase (IKK), As a genetic approach to dissect the intermediate steps involved in NF-kappa B activation in human T cells, me performed somatic cell mutagenesis to isolate signaling-defective mutant Jurkat T-cell lines, One of the mutant cell lines was shown to have a specific blockade in the IKK signaling pathway but remained competent in the c-Jun N-terminal kinase and MAP kinase pathways. Interestingly, this mutant cell line lacks expression of IKK gamma, a non-catalytic component of the IKK complex, Expression of exogenous IKK gamma in the mutant cells restored NF-kappa B activation by both the T-cell costimulation agents and Tax. These findings provide genetic evidence for the requirement of IKK gamma in NF-kappa B signaling triggered by both T-cell costimulatory signals and HTLV-I Tax protein.