Crystal structure of a soluble CD28-Fab complex.

Journal article

Naive T cell activation requires signaling by the T cell receptor and by nonclonotypic cell surface receptors. The most important costimulatory protein is the monovalent homodimer CD28, which interacts with CD80 and CD86 expressed on antigen-presenting cells. Here we present the crystal structure of a soluble form of CD28 in complex with the Fab fragment of a mitogenic antibody. Structural comparisons redefine the evolutionary relationships of CD28-related proteins, antigen receptors and adhesion molecules and account for the distinct ligand-binding and stoichiometric properties of CD28 and the related, inhibitory homodimer CTLA-4. Cryo-electron microscopy-based comparisons of complexes of CD28 with mitogenic and nonmitogenic antibodies place new constraints on models of antibody-induced receptor triggering. This work completes the initial structural characterization of the CD28-CTLA-4-CD80-CD86 signaling system.

Authors: Evans, E; Esnouf, R; Manso-Sancho, R; Gilbert, R; James, JR

• Publication status: Published
• Journal: Nature immunology
• Volume: 6
• Issue: 3
• Pages: 271-279
• Publication date: 2005-03-01
• DOI: 10.1038/ni1170
• EISSN: 1529-2916
• ISSN: 1529-2908
• Language: English
• Keywords: Sequence Alignment; Immunoglobulin Fab Fragments; Animals; Crystallography; Amino Acid Sequence; Models, Molecular; Antigens, CD28; Molecular Sequence Data; Ligands; Immunoconjugates