Journal article
Antigen Ligation Triggers a Conformational Change within the Constant Domain of the αβ T Cell Receptor
T Beddoe, Z Chen, CS Clements, LK Ely, SR Bushell, JP Vivian, L Kjer-Nielsen, SS Pang, MA Dunstone, YC Liu, WA Macdonald, MA Perugini, MCJ Wilce, SR Burrows, AW Purcell, T Tiganis, SP Bottomley, J McCluskey, J Rossjohn
Immunity | Published : 2009
Abstract
Ligation of the αβ T cell receptor (TCR) by a specific peptide-loaded major histocompatibility complex (pMHC) molecule initiates T cell signaling via the CD3 complex. However, the initial events that link antigen recognition to T cell signal transduction remain unclear. Here we show, via fluorescence-based experiments and structural analyses, that MHC-restricted antigen recognition by the αβ TCR results in a specific conformational change confined to the A-B loop within the α chain of the constant domain (Cα). The apparent affinity constant of this A-B loop movement mirrored that of αβ TCR-pMHC ligation and was observed in two αβ TCRs with distinct pMHC specificities. The Ag-induced A-B loop..
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Funding Acknowledgements
We thank N. La Gruta and R. Tweten for useful discussions and D. Garboczi for the generous provision of the A6 TCR plasmids. The Australian Research Council (ARC), the National Health and Medical Research Council of Australia (NHMRC), the Roche Organ Transplantation Research Fund, Monash University Strategic grant, and ANZ trustees supported this research. T.B. is an NHMRC CDA fellow; W.A.M. and M.A.D. are supported by NHMRC Peter Doherty Fellowships; L.K.E. is supported by a NHMRC CJ Martin Fellowship; M.C.J.W., S.R. Burrows, and S.P.B. are supported by a NHMRC Senior Research Fellowship; C.S.C. is supported by an ARC QEII fellowship; and J.R. is supported by an ARC Federation Fellowship.