Alcover A, Mariuzza R A, Ermonval M, Acuto O
Département d'Immunologie, Institut Pasteur, Paris, France.
J Biol Chem. 1990 Mar 5;265(7):4131-5.
The T-cell antigen receptor (TcR) complex present on most T-cells is formed by a clone-specific disulfide-linked alpha/beta heterodimer noncovalently associated to the CD3 complex, the latter composed of five invariant polypeptides: gamma, delta, epsilon, zeta/zeta, or zeta/eta. The presence of conserved, oppositely charged, amino acids in the predicted transmembrane domains of all the subunits of the TcR.CD3 complex suggests that these residues may have a critical function in the assembly and/or stabilization of the complex. In order to analyze the role of the transmembrane-charged amino acids in the association and cell surface expression of the TcR.CD3 complex, we have carried out site-directed mutagenesis of Lys271 in the transmembrane domain of the TcR beta chain and analyzed the capacity of the altered chain to assemble in a TcR beta-negative T-cell line. Here we show that substitution of this positively charged residue by alanine or glutamine does not prevent cytoplasmic association of alpha and beta chains to form disulfide-linked heterodimers, but does abolish formation of an alpha/beta.CD3 complex and, consequently, its expression on the cell surface.
大多数T细胞上存在的T细胞抗原受体（TcR）复合物是由一个克隆特异性的二硫键连接的α/β异二聚体与CD3复合物非共价结合形成的，后者由五种不变多肽组成：γ、δ、ε、ζ/ζ或ζ/η。在TcR.CD3复合物所有亚基的预测跨膜结构域中存在保守的、带相反电荷的氨基酸，这表明这些残基可能在复合物的组装和/或稳定中起关键作用。为了分析跨膜带电荷氨基酸在TcR.CD3复合物的缔合和细胞表面表达中的作用，我们对TcRβ链跨膜结构域中的Lys271进行了定点诱变，并分析了改变后的链在TcRβ阴性T细胞系中组装的能力。我们在此表明，用丙氨酸或谷氨酰胺取代这个带正电荷的残基不会阻止α链和β链在细胞质中缔合形成二硫键连接的异二聚体，但确实会消除α/β.CD3复合物的形成，因此也会消除其在细胞表面的表达。
