Lim J H, Kim S W, Song Y S, Lee S K
Department of Biotechnology, College of Engineering and Bioproducts Research Center, Yonsei University, Seoul, Korea.
Mol Cells. 1998 Aug 31;8(4):408-15.
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-zeta, CD8-Igalpha, CD8-Igbeta, which contain the extracellular and transmembrane domains of the human CD8alpha molecule and the cytoplasmic tail of T-cell receptor (TcR) chain, Igalpha or Igbeta subunit of B-cell receptor, respectively, were stably expressed in a Jurkat cell line. Upon stimulation with anti-CD8 mAb OKT8, CD8-zeta and CD8-Igalpha 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-Igbeta can induce activation of CD69 surface expression and IL-2 gene expression equivalent to the level by CD8-Igalpha and CD8-zeta 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.
T淋巴细胞激活由多个细胞内信号事件组成，最终通过控制细胞因子基因表达和获得多种效应功能来导致细胞增殖。为了研究免疫受体酪氨酸激活基序（ITAM）的功能特异性，分别包含人CD8α分子的胞外和跨膜结构域以及T细胞受体（TcR）链、B细胞受体的Igalpha或Igbeta亚基的胞质尾的嵌合分子CD8-zeta、CD8-Igalpha、CD8-Igbeta在Jurkat细胞系中稳定表达。用抗CD8单克隆抗体OKT8刺激后，CD8-zeta和CD8-Igalpha嵌合蛋白诱导了各种胞质底物的酪氨酸磷酸化，这与TcR刺激时所见相同。它们还能够以依赖于核因子活化T细胞（NF-AT）的方式刺激IL-2基因表达并诱导表面CD69表达。然而，CD8-Igbeta的刺激可以诱导CD69表面表达和IL-2基因表达的激活，其水平与CD8-Igalpha和CD8-zeta相当，但不会诱导细胞内信号分子的酪氨酸磷酸化。这些结果表明，一些含有ITAM的信号链在T细胞激活导致IL-2分泌的过程中可能利用一种不依赖底物酪氨酸磷酸化的信号通路。
