T lymphocyte apoptosis induced by CD8ε chimera

摘要

THE T cell repertoire is characterized by an extremely diverse population of different surface receptors (TCR) which participates in highly specific responses to a large number of different antigens and mediate antigen stimulation signals. Variable heterodimers of TCR α/β and γ/δ receptors are associated with invariable CD3γ, δ, ε and ξ proteins, thus forming the TCR/ CD3 complex. CD3ε plays an important role in the initiation of TCR resembling and signal transduction among the octopeptide chains. Stimulation by anti-CD3ε monoclonal antibody causes the cell death by apoptosis in immature thymocytes, but induces activation, proliferation or anergy in mature T cells. It has been known that the CD3ε activation signals are transferred throughan immune receptor tyrosine-based activation motif (ITAM) in the cytoplasmic region of CD3ε molecule. Ju et al. reported recently that some transformed T cells stimulated by anti-CD3ε monoclonal antibody could undergo apoptosis, termed as activation-induced cell death. However, the molecular mechanisms of apoptotic signal transduction mediated by CD3ε have not been reported. In the present study, a chimera (termed as CD8ε) that fused the extracellular and transmembrane domains of human CD8α to thecytoplasmic domain of CD3ε was constructed. And the chimera was stably expressed in human leukemia CD8α~-Jurkat cells after transfection. It was found that the chimera could transfer apoptotic signals and mediate cell death of the Jurkat cells stimulated by anti-CD8α monoclonal antibody, suggesting that there may be a death motif as well as an activation motif in the cytoplasmic domain of the CD3ε molecule.