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.
Original language | English |
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Pages (from-to) | 195-202 |
Number of pages | 8 |
Journal | Immunology Letters |
Volume | 116 |
Issue number | 2 |
DOIs | |
Publication status | Published - 15 Mar 2008 |
Keywords
- Activation
- Conformational change
- Signalling
- T cell antigen receptor
- TCR zeta chain
- TCR-CD3 complex
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology