Molecular mechanisms in lymphocyte activation and growth

Transcription factor NF-kappaB is biochemically coupled to the T cell antig en receptor (TCR) and activated transiently during an adaptive immune respo nse. The author's laboratory is investigating the signal dependent regulati on of NF-kappaB, its downstream gene targets, and its function in lymphocyt e biology. Our studies have revealed novel enzymatic checkpoints in the NF- kappaB signaling pathway and constitutive repressors of NF-kappaB that migh t 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 I (HTLV1)binds to and persistently activates an inducib le protein kinase in the TCR/NF-kappaB axis. This viral/host interaction ap pears to trigger the inappropriate expression of NF-kappaH and the developm ent of HTLV I-associated disease.