Crystal structure of a soluble CD28-Fab complex.
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.
Evans
Edward J
EJ
Nuffield Department of Clinical Medicine, The University of Oxford, John Radcliffe Hospital, Headington, Oxford, OX3 9DU, UK.
Esnouf
Robert M
RM
Manso-Sancho
Raquel
R
Gilbert
Robert J C
RJ
James
John R
JR
Yu
Chao
C
Fennelly
Janet A
JA
Vowles
Cheryl
C
Hanke
Thomas
T
Walse
Björn
B
Hünig
Thomas
T
Sørensen
Poul
P
Stuart
David I
DI
Davis
Simon J
SJ
D000069594:Abatacept; D000595:Amino Acid Sequence; D000818:Animals; D018106:CD28 Antigens / Q000737:chemistry* / Q000235:genetics / Q000276:immunology; D003461:Crystallography; D018796:Immunoconjugates / Q000378:metabolism; D007140:Immunoglobulin Fab Fragments / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D008024:Ligands; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016415:Sequence Alignment
D018106:CD28 Antigens; D018796:Immunoconjugates; D007140:Immunoglobulin Fab Fragments; D008024:Ligands; D000069594:Abatacept