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.

Original publication

DOI

10.1038/ni1170

Type

Journal article

Journal

Nature immunology

Publication Date

03/2005

Volume

6

Pages

271 - 279

Addresses

Nuffield Department of Clinical Medicine, The University of Oxford, John Radcliffe Hospital, Headington, Oxford, OX3 9DU, UK.

Keywords

Animals, Antigens, CD28, Immunoconjugates, Ligands, Crystallography, Sequence Alignment, Amino Acid Sequence, Models, Molecular, Molecular Sequence Data, Immunoglobulin Fab Fragments