T Cell Division and Death Are Segregated by Mutation of TCRβ Chain Constant Domains

AbstractWe have studied the role of the T cell receptor (TCR) β chain transmembrane and cytoplasmic domains (βTM/Cyto) in T cell signaling. Upon antigen stimulation, T lymphocytes expressing a TCR with mutant and βTM and Cyto domains accumulate in large numbers and are specifically defective in undergoing activation-induced cell death (AICD). The mutant TCR poorly recruits the protein adaptor Carma-1 and is subsequently impaired in activating NF-κB. This signaling defect leads to a reduced expression of Fas ligand (FasL) and to a reduction in AICD. These β chain domains are involved in discriminating cell division and apoptosis