Barz C, Nagel T, Truitt K E, Imboden J B
Department of Medicine, San Francisco General Hospital, CA 94110, USA.
J Immunol. 1998 Nov 15;161(10):5366-72.
The accessory molecule CD28 delivers a costimulus that acts in concert with TCR signals to promote T cell activation. Activation of Jun-N-terminal kinases (JNK) requires simultaneous stimulation of the TCR and CD28 and, therefore, likely plays an important role in signal integration during costimulation. We investigated the effects of mutations in the 41-amino acid cytoplasmic domain of murine CD28 on its ability to deliver costimuli for JNK activation and IL-2 production when expressed in Jurkat T cells. Our results indicate that the costimulus for JNK activation requires the membrane-proximal 24 amino acids of the CD28 cytoplasmic domain and is not mediated by the tyrosine-based recruitment of signaling molecules, including phosphatidylinositol 3-kinase. Deletion of the carboxyl-terminal 17 amino acids does not affect the ability of CD28 to augment JNK activation but impairs its ability to enhance TCR-mediated production of IL-2, demonstrating that optimal costimulation of IL-2 production requires CD28 signals in addition to the activation of JNK.
辅助分子CD28传递一种共刺激信号，该信号与T细胞受体（TCR）信号协同作用，以促进T细胞活化。Jun氨基末端激酶（JNK）的激活需要同时刺激TCR和CD28，因此，JNK可能在共刺激过程中的信号整合中发挥重要作用。我们研究了小鼠CD28的41个氨基酸的胞质结构域中的突变对其在Jurkat T细胞中表达时传递共刺激信号以激活JNK和产生白细胞介素-2（IL-2）能力的影响。我们的结果表明，激活JNK的共刺激信号需要CD28胞质结构域中靠近膜的24个氨基酸，且不是由包括磷脂酰肌醇3激酶在内的基于酪氨酸的信号分子募集介导的。羧基末端17个氨基酸的缺失不影响CD28增强JNK激活的能力，但损害其增强TCR介导的IL-2产生的能力，这表明IL-2产生的最佳共刺激除了JNK激活外还需要CD28信号。
