The short length of the extracellular domain of zeta is crucial for T cell antigen receptor function.
The T cell antigen receptor (TCR-CD3) consists of the pMHC-binding TCRalphabeta heterodimer and the signalling dimers CD3deltaepsilon, CD3gammaepsilon and zetazeta. The very short length of the extracellular domain (EC) of the zeta 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 zeta 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 zeta EC domains underwent ligand-induced conformation changes with higher efficiency than TCR-CD3 complexes with an unmodified zeta EC domain. Together these data suggest that a short zeta 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.
Minguet
Susana
S
Max Planck Institute of Immunbiology and Faculty of Biology III, University of Freiburg, Stübeweg 51, 79108 Freiburg, Germany.
Swamy
Mahima
M
Schamel
Wolfgang W A
WW
D000595:Amino Acid Sequence; D000818:Animals; D017252:CD3 Complex / Q000737:chemistry* / Q000276:immunology*; D002460:Cell Line; D019281:Dimerization; D015870:Gene Expression; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000737:chemistry* / Q000276:immunology*; D011994:Recombinant Proteins; D016415:Sequence Alignment; D015398:Signal Transduction / Q000276:immunology
D017252:CD3 Complex; C121704:CD3 antigen, zeta chain; D017260:Receptor-CD3 Complex, Antigen, T-Cell; D011994:Recombinant Proteins