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Title: Divergent T-cell receptor recognition modes of a HLA-I restricted extended tumour-associated peptide.
Austin Authors: Chan, Kok Fei;Gully, Benjamin S;Gras, Stephanie;Beringer, Dennis X;Kjer-Nielsen, Lars;Cebon, Jonathan S ;McCluskey, James;Chen, Weisan;Rossjohn, Jamie
Affiliation: Olivia Newton-John Cancer Research Institute, Heidelberg, Victoria, Australia
School of Cancer Medicine, La Trobe University, Melbourne, Victoria, Australia
Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Parkville, Victoria, Australia
Infection and Immunity Program and Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia
Department of Biochemistry & Genetics, La Trobe Institute of Molecular Science, La Trobe University, Bundoora, Victoria, Australia
Australian Research Council Centre of Excellence for Advanced Molecular Imaging, Monash University, Clayton, Victoria, Australia
Institute of Infection and Immunity, Cardiff University School of Medicine, Heath Park, Cardiff, UK
Issue Date: 2018
Date: 2018-03-12
Publication information: Nature Communications 2018; 9(1): 1026
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 complex, and induces differing extent of conformational change of the NY-ESO-160-72 epitope. Accordingly, polyclonal TCR usage towards an extended HLA-I restricted tumour epitope translates to differing TCR recognition modes, whereby extensive flexibility at the TCR-pHLA-I interface engenders recognition.
DOI: 10.1038/s41467-018-03321-w
ORCID: 0000-0001-7383-6544
Journal: Nature Communications
PubMed URL: 29531227
Type: Journal Article
Appears in Collections:Journal articles

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