Journal article
Divergent T-cell receptor recognition modes of a HLA-I restricted extended tumour-associated peptide
KF Chan, BS Gully, S Gras, DX Beringer, L Kjer-Nielsen, J Cebon, J McCluskey, W Chen, J Rossjohn
Nature Communications | NATURE PUBLISHING GROUP | Published : 2018
Abstract
Human leukocyte antigen (HLA)-I molecules generally bind short peptides (8-10 amino acids), although extended HLA-I restricted peptides (>10 amino acids) can be presented to T cells. However, the function of such extended HLA-I epitopes in tumour immunity, and how they would be recognised by T-cell receptors (TCR) remains unclear. Here we show that the structures of two distinct TCRs (TRAV4+TRAJ21+-TRBV28+TRBJ2-3+ and TRAV4 + TRAJ8+-TRBV9+TRBJ2-1+), originating from a polyclonal T-cell repertoire, bind to HLA-B∗07:02, presenting a 13-amino-acid-long tumour-associated peptide, NY-ESO-160-72. Comparison of the structures reveals that the two TCRs differentially binds NY-ESO-160-72-HLA-B∗07:02 ..
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Funding Acknowledgements
We thank the Monash Macromolecular Crystallisation Facility staff for assistance with crystallisation, the staff at the Australian synchrotron for assistance with data collection and Hanim Halim, Kristy Campbell and Pascal Wilmann for technical assistance. This work was supported by the Australian Research Council, National Health and Medical Research Council, Ludwig Cancer Research and the Operational Infrastructure Support program of the Victorian State Government. S.G. is a Monash Senior Research Fellow. J.R. is supported by an ARC Laureate Fellowship.