Molecular mechanisms in lymphocyte activation and growth.

Transcription factor NF-kappaB is biochemically coupled to the T cell antigen receptor (TCR) and activated transiently during an adaptive immune response. The author's laboratory is investigating the signal-dependent regulation of NF-kappaB, its downstream gene targets, and its function in lymphocyte biology. Our studies have revealed novel enzymatic checkpoints in the NF-kappaB signaling pathway and constitutive repressors of NF-kappaB that might be clinically applicable for therapeutic control of the immune system. We have also found that the Tax transforming protein encoded by human T cell leukemia virus type 1 (HTLV1) binds to and persistently activates an inducible protein kinase in the TCR/NF-kappaB axis. This viral/host interaction appears to trigger the inappropriate expression of NF-kappaB and the development of HTLV1-associated disease.