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Divergent T-cell receptor recognition modes of a HLA-I restricted extended tumour-associated peptide.

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.

SUBMITTER: Chan KF

PROVIDER: S-EPMC5847591 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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Divergent T-cell receptor recognition modes of a HLA-I restricted extended tumour-associated peptide.

Chan Kok Fei KF Gully Benjamin S BS Gras Stephanie S Beringer Dennis X DX Kjer-Nielsen Lars L Cebon Jonathan J McCluskey James J Chen Weisan W Rossjohn Jamie J

Nature communications 20180312 1

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+</su ...[more]

PMID: 29531227

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Dataset Information

Divergent T-cell receptor recognition modes of a HLA-I restricted extended tumour-associated peptide.

Publications

Divergent T-cell receptor recognition modes of a HLA-I restricted extended tumour-associated peptide.

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