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Free keywords:
T cell antigen receptor; TCR-CD3 complex; TCR zeta chain; Conformation change; Signalling; Activation
Abstract:
The T cell antigen receptor (TCR-CD3) consists of the pMHC-binding TCRαβ heterodimer and the signalling dimers CD3δε, CD3γε 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.
