Merćep M, Bonifacino J S, Garcia-Morales P, Samelson L E, Klausner R D, Ashwell J D
Biological Response Modifiers Program, National Cancer Institute, Bethesda, MD 20892.
Science. 1988 Oct 28;242(4878):571-4. doi: 10.1126/science.2845582.
The T cell antigen receptor consists of an antigen-binding heterodimer that is noncovalently associated with at least five CD3 subunits (gamma, delta, epsilon, zeta, and eta). The CD3-zeta chains are either disulfide-linked homodimers (CD3-zeta 2) or disulfide-linked heterodimers with eta (CD3-zeta eta). Variants of a murine antigen-specific T cell hybridoma that express normal amounts of CD3-zeta 2 but decreased amounts of CD3-zeta eta were isolated. When activated, the parental cell line increased both phosphatidylinositol hydrolysis and serine-specific protein kinase activity to a much greater extent than the variants. In contrast, the activation of a tyrosine-specific kinase after stimulation with a cross-linking antibody to CD3 was similar among these cells. There was a positive linear relation between the expression of CD3-zeta eta and phosphoinositide hydrolysis stimulated by the TCR, suggesting a differential coupling of the T cell alpha beta heterodimer to signal transduction mechanisms due to alpha beta association with either CD3-zeta 2 or CD3-zeta eta.
T细胞抗原受体由一个抗原结合异二聚体组成，该异二聚体与至少五个CD3亚基（γ、δ、ε、ζ和η）非共价结合。CD3-ζ链要么是二硫键连接的同二聚体（CD3-ζ2），要么是与η形成的二硫键连接的异二聚体（CD3-ζη）。分离出了表达正常量的CD3-ζ2但CD3-ζη量减少的鼠源抗原特异性T细胞杂交瘤变体。激活时，亲代细胞系的磷脂酰肌醇水解和丝氨酸特异性蛋白激酶活性增加的程度比变体大得多。相反，在用抗CD3交联抗体刺激后，这些细胞中酪氨酸特异性激酶的激活情况相似。CD3-ζη的表达与TCR刺激的磷酸肌醇水解之间存在正线性关系，这表明由于αβ与CD3-ζ2或CD3-ζη的结合，T细胞αβ异二聚体与信号转导机制的偶联存在差异。
