Apoptosis but not other activation events is inhibited by a mutation in the transmembrane domain of T cell receptor beta that impairs CD3zeta association.

The Journal of Biological Chemistry
G Rodríguez-TarduchyR Bragado

Abstract

The transmembrane domain of T cell receptor (TCR) beta contains a conserved immunoreceptor tyrosine-based activation-like motif consisting of a duplicated YXXL sequence. The motif is also present in TCRgamma, the equivalent chain to TCRbeta in gammadelta T lymphocytes but is absent in TCRalpha and TCRdelta. To determine the putative role of this sequence in TCR.CD3 complex assembly and signal transduction, a TCRbeta chain cDNA was mutated in the C-terminal tyrosine of the motif, cloned in an expression vector, and transfected into TCRbeta-negative Jurkat cells. Transfectants of the mutated chain (MUT) expressed, on average, much less TCR.CD3 complex on the membrane than wild type TCRbeta transfectants. Radiolabeling experiments suggested that the mutation caused a loose association of the CD3zeta chain resulting in a defective assembly. However, stimulation of high TCR.CD3 expressing wild type and MUT clones with monoclonal antibodies and Staphylococcus aureus enterotoxin B resulted in similar levels of CD25 and CD69 expression, interleukin-2 secretion, and TCR.CD3 complex down-regulation. By contrast, MUT cells were clearly resistant to activation-induced cell death, and they did not express CD95-ligand upon activation. These ...Continue Reading

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Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis