Apoptosis in a Fas-resistant, T-cell receptor-sensitive human leukaemic T-cell clone.

The Fas (CD95) antigen plays a key role in regulating T-cell activation and survival. We have generated a Fas-resistant subclone of the human T-cell leukaemia line, H9, which is still able to undergo apoptosis in response to T-cell receptor ligation. Molecular analyses revealed that resistance to Fas-mediated apoptosis was due to a heterozygous mutation in the death domain of the Fas gene which generates a stop codon, and thus encodes a truncated Fas molecule. Fas ligation was able to induce apoptosis in the presence of cycloheximide, indicating that the mutant Fas molecule retained some signalling capability, which is death-domain independent. These cells will provide a useful tool for dissecting the complexities of Fas signalling pathways.