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

Carin C. Stamper, Yan Zhang, James F. Tobin, David V. Erbe, Shinji Ikemizu, Simon J. Davis, Mark L. Stahl, Jasbir Seehra, William S. Somers () and Lidia Mosyak
Additional contact information
Carin C. Stamper: Wyeth Research
Yan Zhang: Wyeth Research
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

Nature, 2001, vol. 410, issue 6828, 608-611

Abstract: 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.

Date: 2001
References: Add references at CitEc
Citations: View citations in EconPapers (3)

Downloads: (external link)
https://www.nature.com/articles/35069118 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:410:y:2001:i:6828:d:10.1038_35069118

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/35069118

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().