IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v11y2020i1d10.1038_s41467-020-16755-y.html
   My bibliography  Save this article

Structural basis for oligoclonal T cell recognition of a shared p53 cancer neoantigen

Author

Listed:
  • Daichao Wu

    (University of Maryland Institute for Bioscience and Biotechnology Research
    University of South China
    University of Maryland)

  • D. Travis Gallagher

    (University of Maryland Institute for Bioscience and Biotechnology Research
    National Institute of Standards and Technology)

  • Ragul Gowthaman

    (University of Maryland Institute for Bioscience and Biotechnology Research
    University of Maryland)

  • Brian G. Pierce

    (University of Maryland Institute for Bioscience and Biotechnology Research
    University of Maryland)

  • Roy A. Mariuzza

    (University of Maryland Institute for Bioscience and Biotechnology Research
    University of Maryland)

Abstract

Adoptive cell therapy (ACT) with tumor-specific T cells can mediate cancer regression. The main target of tumor-specific T cells are neoantigens arising from mutations in self-proteins. Although the majority of cancer neoantigens are unique to each patient, and therefore not broadly useful for ACT, some are shared. We studied oligoclonal T-cell receptors (TCRs) that recognize a shared neoepitope arising from a driver mutation in the p53 oncogene (p53R175H) presented by HLA-A2. Here we report structures of wild-type and mutant p53–HLA-A2 ligands, as well as structures of three tumor-specific TCRs bound to p53R175H–HLA-A2. These structures reveal how a driver mutation in p53 rendered a self-peptide visible to T cells. The TCRs employ structurally distinct strategies that are highly focused on the mutation to discriminate between mutant and wild-type p53. The TCR–p53R175H–HLA-A2 complexes provide a framework for designing TCRs to improve potency for ACT without sacrificing specificity.

Suggested Citation

  • Daichao Wu & D. Travis Gallagher & Ragul Gowthaman & Brian G. Pierce & Roy A. Mariuzza, 2020. "Structural basis for oligoclonal T cell recognition of a shared p53 cancer neoantigen," Nature Communications, Nature, vol. 11(1), pages 1-12, December.
  • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-16755-y
    DOI: 10.1038/s41467-020-16755-y
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-020-16755-y
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-020-16755-y?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Andrew Poole & Vijaykumar Karuppiah & Annabelle Hartt & Jaafar N. Haidar & Sylvie Moureau & Tomasz Dobrzycki & Conor Hayes & Christopher Rowley & Jorge Dias & Stephen Harper & Keir Barnbrook & Miriam , 2022. "Therapeutic high affinity T cell receptor targeting a KRASG12D cancer neoantigen," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    2. Katharine M. Wright & Sarah R. DiNapoli & Michelle S. Miller & P. Aitana Azurmendi & Xiaowei Zhao & Zhiheng Yu & Mayukh Chakrabarti & WuXian Shi & Jacqueline Douglass & Michael S. Hwang & Emily Han-Ch, 2023. "Hydrophobic interactions dominate the recognition of a KRAS G12V neoantigen," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    3. Cecily Choy & Joseph Chen & Jiangyuan Li & D. Travis Gallagher & Jian Lu & Daichao Wu & Ainslee Zou & Humza Hemani & Beverly A. Baptiste & Emily Wichmann & Qian Yang & Jeffrey Ciffelo & Rui Yin & Juli, 2023. "SARS-CoV-2 infection establishes a stable and age-independent CD8+ T cell response against a dominant nucleocapsid epitope using restricted T cell receptors," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    4. 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.
    5. John P. Finnigan & Jenna H. Newman & Yury Patskovsky & Larysa Patskovska & Andrew S. Ishizuka & Geoffrey M. Lynn & Robert A. Seder & Michelle Krogsgaard & Nina Bhardwaj, 2024. "Structural basis for self-discrimination by neoantigen-specific TCRs," Nature Communications, Nature, vol. 15(1), pages 1-18, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-16755-y. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.