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

Author

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  • Kok Fei Chan

    (La Trobe University
    The University of Melbourne
    Monash University
    La Trobe University)

  • Benjamin S. Gully

    (Monash University
    Monash University)

  • Stephanie Gras

    (Monash University
    Monash University)

  • Dennis X. Beringer

    (Monash University)

  • Lars Kjer-Nielsen

    (The University of Melbourne)

  • Jonathan Cebon

    (La Trobe University)

  • James McCluskey

    (The University of Melbourne)

  • Weisan Chen

    (La Trobe University
    La Trobe University)

  • Jamie Rossjohn

    (Monash University
    Monash University
    Cardiff University School of Medicine)

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.

Suggested Citation

  • Kok Fei Chan & Benjamin S. Gully & Stephanie Gras & Dennis X. Beringer & Lars Kjer-Nielsen & Jonathan Cebon & James McCluskey & Weisan Chen & Jamie Rossjohn, 2018. "Divergent T-cell receptor recognition modes of a HLA-I restricted extended tumour-associated peptide," Nature Communications, Nature, vol. 9(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-03321-w
    DOI: 10.1038/s41467-018-03321-w
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    Cited by:

    1. Catarina F. Almeida & Benjamin S. Gully & Claerwen M. Jones & Lukasz Kedzierski & Sachith D. Gunasinghe & Michael T. Rice & Richard Berry & Nicholas A. Gherardin & Trang T. Nguyen & Yee-Foong Mok & Jo, 2024. "Direct recognition of an intact foreign protein by an αβ T cell receptor," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    2. Tejas Menon & Patricia T. Illing & Priyanka Chaurasia & Hayley A. McQuilten & Chloe Shepherd & Louise C. Rowntree & Jan Petersen & Dene R. Littler & Grace Khuu & Ziyi Huang & Lilith F. Allen & Steve R, 2024. "CD8+ T-cell responses towards conserved influenza B virus epitopes across anatomical sites and age," Nature Communications, Nature, vol. 15(1), pages 1-21, December.
    3. Nishant K. Singh & Jesus A. Alonso & Jason R. Devlin & Grant L. J. Keller & George I. Gray & Adarsh K. Chiranjivi & Sara G. Foote & Lauren M. Landau & Alyssa G. Arbuiso & Laura I. Weiss & Aaron M. Ros, 2022. "A class-mismatched TCR bypasses MHC restriction via an unorthodox but fully functional binding geometry," Nature Communications, Nature, vol. 13(1), pages 1-14, December.

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