IDEAS home Printed from https://ideas.repec.org/a/nat/nature/v410y2001i6828d10.1038_35069118.html
   My bibliography  Save this article

Crystal structure of the B7-1/CTLA-4 complex that inhibits human immune responses

Author

Listed:
  • Carin C. Stamper

    (Wyeth Research)

  • Yan Zhang

    (Wyeth Research
    Pfizer Cambridge Discovery Technology Center)

  • James F. Tobin

    (Wyeth Research)

  • David V. Erbe

    (Wyeth Research)

  • Shinji Ikemizu

    (The Henry Wellcome Building for Genomic Medicine, The University of Oxford)

  • Simon J. Davis

    (The University of Oxford, John Radcliffe Hospital)

  • Mark L. Stahl

    (Wyeth Research)

  • Jasbir Seehra

    (Wyeth Research)

  • William S. Somers

    (Wyeth Research)

  • Lidia Mosyak

    (Wyeth Research)

Abstract

Optimal immune responses require both an antigen-specific and a co-stimulatory signal. The shared ligands B7-1 and B7-2 on antigen-presenting cells deliver the co-stimulatory signal through CD28 and CTLA-4 on T cells. Signalling through CD28 augments the T-cell response, whereas CTLA-4 signalling attenuates it. Numerous animal studies1,2 and recent clinical trials3,4 indicate that manipulating these interactions holds considerable promise for immunotherapy. With the consequences of these signals well established, and details of the downstream signalling events emerging5,6,7, understanding the molecular nature of these extracellular interactions becomes crucial. Here we report the crystal structure of the human CTLA-4/B7-1 co-stimulatory complex at 3.0 Å resolution. In contrast to other interacting cell-surface molecules, the relatively small CTLA-4/B7-1 binding interface exhibits an unusually high degree of shape complementarity. CTLA-4 forms homodimers through a newly defined interface of highly conserved residues. In the crystal lattice, CTLA-4 and B7-1 pack in a strikingly periodic arrangement in which bivalent CTLA-4 homodimers bridge bivalent B7-1 homodimers. This zipper-like oligomerization provides the structural basis for forming unusually stable signalling complexes at the T-cell surface, underscoring the importance of potent inhibitory signalling in human immune responses.

Suggested Citation

  • Carin C. Stamper & Yan Zhang & James F. Tobin & David V. Erbe & Shinji Ikemizu & Simon J. Davis & Mark L. Stahl & Jasbir Seehra & William S. Somers & Lidia Mosyak, 2001. "Crystal structure of the B7-1/CTLA-4 complex that inhibits human immune responses," Nature, Nature, vol. 410(6828), pages 608-611, March.
  • Handle: RePEc:nat:nature:v:410:y:2001:i:6828:d:10.1038_35069118
    DOI: 10.1038/35069118
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/35069118
    File Function: Abstract
    Download Restriction: Access to the full text of the articles in this series is restricted.

    File URL: https://libkey.io/10.1038/35069118?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
    ---><---

    As the access to this document is restricted, you may want to search for a different version of it.

    Citations

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


    Cited by:

    1. Mark F. Maurer & Katherine E. Lewis & Joseph L. Kuijper & Dan Ardourel & Chelsea J. Gudgeon & Siddarth Chandrasekaran & Sherri L. Mudri & Kayla N. Kleist & Chris Navas & Martin F. Wolfson & Mark W. Ri, 2022. "The engineered CD80 variant fusion therapeutic davoceticept combines checkpoint antagonism with conditional CD28 costimulation for anti-tumor immunity," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    2. Jan Bláha & Tereza Skálová & Barbora Kalousková & Ondřej Skořepa & Denis Cmunt & Valéria Grobárová & Samuel Pazicky & Edita Poláchová & Celeste Abreu & Jan Stránský & Tomáš Kovaľ & Jarmila Dušková & Y, 2022. "Structure of the human NK cell NKR-P1:LLT1 receptor:ligand complex reveals clustering in the immune synapse," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    3. Shangyu Yang & Yong Wang & Feiyang Yu & Rao Cheng & Yiwei Zhang & Dan Zhou & Xuanxiu Ren & Zengqin Deng & Haiyan Zhao, 2023. "Structural and functional insights into the modulation of T cell costimulation by monkeypox virus protein M2," Nature Communications, Nature, vol. 14(1), pages 1-13, 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:nature:v:410:y:2001:i:6828:d:10.1038_35069118. 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.