The short length of the extracellular domain of ζ is crucial for T cell antigen receptor function
- 作者：Susana Minguet ; Mahima Swamy ; Wolfgang W.A. Schamel
- 关键词：T cell antigen receptor ; TCR-CD3 complex ; TCR zeta chain ; Conformational change ; Signalling ; Activation
- 刊名：Immunology Letters
- 出版年：2008
- 期刊代码：115_01652478
- 类别：med
- 出版时间：15 March 2008
- 卷：116
- 期：2
- 页码：195-202
- 文件大小：733 K
摘要
The T cell antigen receptor (TCR-CD3) consists of the pMHC-binding TCR
β heterodimer and the signalling dimers CD3δ
, CD3γ and ζζ. The very short length of the extracellular domain (EC) of the ζ chain is preserved through evolution, however a rational explanation for this observation has not been elucidated. Here, we show that TCR-CD3 assembly is clearly defective when the murine ζ EC domain is artificially enlarged. Under these conditions, the TCR-CD3 complex is super-competent in transducing activation signals upon engagement. Furthermore, the TCR-CD3 complexes containing enlarged ζ EC domains underwent ligand-induced conformation changes with higher efficiency than TCR-CD3 complexes with an unmodified ζ EC domain. Together these data suggest that a short ζ EC domain is needed to correctly assemble the TCR-CD3 complex. When this domain is enlarged, the resulting TCR-CD3 complex is distorted leading to a hyperactive phenotype and enhanced T cell activation.
β heterodimer and the signalling dimers CD3δ, CD3γ and ζζ. The very short length of the extracellular domain (EC) of the ζ chain is preserved through evolution, however a rational explanation for this observation has not been elucidated. Here, we show that TCR-CD3 assembly is clearly defective when the murine ζ EC domain is artificially enlarged. Under these conditions, the TCR-CD3 complex is super-competent in transducing activation signals upon engagement. Furthermore, the TCR-CD3 complexes containing enlarged ζ EC domains underwent ligand-induced conformation changes with higher efficiency than TCR-CD3 complexes with an unmodified ζ EC domain. Together these data suggest that a short ζ EC domain is needed to correctly assemble the TCR-CD3 complex. When this domain is enlarged, the resulting TCR-CD3 complex is distorted leading to a hyperactive phenotype and enhanced T cell activation.