T-lymphocyte activation consists of multiple intracellular signaling events, eventually leading to cellular proliferation by the control of cytokine gene expression and the acquisition of diverse effector function. To investigate the functional specificity of ITAM (Immunoreceptor Tyrosine-based Activation Motif), chimeric molecules CD8-ζ, CD8-Igα, CD8-Igβ, which contain the extracellular and transmembrane domains of the human CD8α molecule and the cytoplasmic tail of T-cell receptor (TcR) ζ chain, Igα or Igβ subunit of B-cell receptor, respectively, were stably expressed in a Jurkat cell line. Upon stimulation with anti-CD8 mAb OKT8, CD8-ζ and CD8-Igα chimeric proteins induced tyrosine phosphorylation of various cytoplasmic substrates as seen in TcR stimulation. They were also capable of stimulating IL-2 gene expression in a NF-AT dependent manner and inducing CD69 expression on the surface. However, stimulation of CD8-Igβ can induce activation of CD69 surface expression and IL-2 gene expression equivalent to the level by CD8-Igα and CD8-ζ without induction of the tyrosine phosphorylation of intracellular signaling molecules. These results suggested that some of signaling chains containing ITAM may utilize a signal pathway without substrate tyrosine phosphorylation during T-cell activation leading to the IL-2 secretion.
Number of pages|
Molecules and cells|
Published - 1998 Aug 31|
All Science Journal Classification (ASJC) codes