Journal article

Molecular architecture of the alpha beta T cell receptor-CD3 complex

Michael E Birnbaum, Richard Berry, Yu-Shan Hsiao, Zhenjun Chen, Miguel A Shingu-Vazquez, Xiaoling Yu, Deepa Waghray, Suzanne Fischer, James McCluskey, Jamie Rossjohn, Thomas Walz, K Christopher Garcia

Proceedings of the National Academy of Sciences of the United States of America | NATL ACAD SCIENCES | Published : 2014

Abstract

αβ T-cell receptor (TCR) activation plays a crucial role for T-cell function. However, the TCR itself does not possess signaling domains. Instead, the TCR is noncovalently coupled to a conserved multisubunit signaling apparatus, the CD3 complex, that comprises the CD3εγ, CD3εδ, and CD3ζζ dimers. How antigen ligation by the TCR triggers CD3 activation and what structural role the CD3 extracellular domains (ECDs) play in the assembled TCR-CD3 complex remain unclear. Here, we use two complementary structural approaches to gain insight into the overall organization of the TCR-CD3 complex. Small-angle X-ray scattering of the soluble TCR-CD3εδ complex reveals the CD3εδ ECDs to sit underneath the T..

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Grants

Awarded by National Health and Medical Research Council (NHMRC)


Awarded by NIH


Awarded by NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES


Funding Acknowledgements

We thank Ignacio Moraga, Michael Kuhns, and Mark Davis for helpful discussions; Dr. Eric Hanssen and the staff at the Australian synchrotron for assistance with data collection; and Lars Kjer-Nielsen for establishing a number of the systems underpinning this work. This work was supported by a Regina Casper Stanford Graduate Fellowship (to M.E.B.), a Gerald J. Lieberman Fellowship (to M.E.B.), a National Science Foundation Graduate Fellowship (to M.E.B.), National Health and Medical Research Council (NHMRC) Peter Doherty Fellowship GNT1035636 (to R.B.), an NHMRC Australia Fellowship (to J.R.), NIH Grant R01 AI03867 (to K.C.G.), and Howard Hughes Medical Institute (T.W. and K.C.G.), NHMRC (J.R. and J. M.), and Australian Research Council (J.R. and J.M.).