The short length of the extracellular domain of zeta is crucial for T cell antigen receptor function

Immunology Letters
Susana MinguetWolfgang W A Schamel

Abstract

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.

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Citations

Mar 20, 2010·Cell Communication and Signaling : CCS·Mahima SwamyWolfgang Wa Schamel
Nov 26, 2014·Proceedings of the National Academy of Sciences of the United States of America·Michael E BirnbaumK Christopher Garcia
Oct 11, 2012·Immunological Reviews·Michael S Kuhns, Hemant B Badgandi
Jan 30, 2013·The Journal of Immunology : Official Journal of the American Association of Immunologists·Sumit DeswalWolfgang W A Schamel
Aug 14, 2019·Immunological Reviews·Wolfgang W SchamelSusana Minguet
Jul 31, 2013·Biochimica Et Biophysica Acta·Ariel Alcides PetrukUmberto Oreste
Jan 25, 2008·Immunology Letters·Susana MinguetWolfgang W A Schamel

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