TY - JOUR
T1 - The short length of the extracellular domain of ζ is crucial for T cell antigen receptor function
AU - Minguet, Susana
AU - Swamy, Mahima
AU - Schamel, Wolfgang W.A.
PY - 2008/3/15
Y1 - 2008/3/15
N2 - 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.
AB - 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.
KW - Activation
KW - Conformational change
KW - Signalling
KW - T cell antigen receptor
KW - TCR zeta chain
KW - TCR-CD3 complex
UR - http://www.scopus.com/inward/record.url?scp=40149095444&partnerID=8YFLogxK
U2 - 10.1016/j.imlet.2007.11.020
DO - 10.1016/j.imlet.2007.11.020
M3 - Article
C2 - 18207249
AN - SCOPUS:40149095444
VL - 116
SP - 195
EP - 202
JO - Immunology Letters
JF - Immunology Letters
SN - 0165-2478
IS - 2
ER -