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.
Delehanty
L L
LL
Department of Cell Physiology, Glaxo Research Institute, Glaxo Inc., Research Triangle Park, NC, USA.
Payne
J A
JA
Farrow
S N
SN
Brown
R
R
Champion
B R
BR
D000595:Amino Acid Sequence; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics / Q000276:immunology*; D003513:Cycloheximide / Q000494:pharmacology; D006801:Humans; D015458:Leukemia, T-Cell / Q000276:immunology*; D008969:Molecular Sequence Data; D009154:Mutation; D014411:Neoplastic Stem Cells / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D016559:Tacrolimus / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D019014:fas Receptor / Q000235:genetics / Q000276:immunology*
D011948:Receptors, Antigen, T-Cell; D019014:fas Receptor; D003513:Cycloheximide; D016559:Tacrolimus