Crystal structure of the human T cell receptor CD3 epsilon gamma heterodimer complexed to the therapeutic mAb OKT3.
The CD3 epsilon gamma heterodimer is essential for expression and function of the T cell receptor. The crystal structure of the human CD3 epsilon gamma heterodimer is described to 2.1-A resolution complexed with OKT3, a therapeutic mAb that not only activates and tolerizes mature T cells but also induces regulatory T cells. The mode of CD3 epsilon gamma dimerization provides a general structural basis for CD3 assembly and maps candidate T cell antigen receptor docking sites, including a duplicated linear region rich in acidic residues that is unique to human CD3 epsilon. OKT3 binds to an atypically small area of CD3 epsilon and has a low affinity for the isolated CD3 epsilon gamma heterodimer. The structure of the OKT3/CD3 epsilon gamma complex has implications for T cell signaling and therapeutic design.
Kjer-Nielsen
Lars
L
Department of Microbiology and Immunology, University of Melbourne, Parkville, Victoria 3010, Australia.
Dunstone
Michelle A
MA
Kostenko
Lyudmila
L
Ely
Lauren K
LK
Beddoe
Travis
T
Mifsud
Nicole A
NA
Purcell
Anthony W
AW
Brooks
Andrew G
AG
McCluskey
James
J
Rossjohn
Jamie
J
D000595:Amino Acid Sequence; D000818:Animals; D017252:CD3 Complex / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism; D003460:Crystallization; D019281:Dimerization; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D016853:Muromonab-CD3 / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D020349:Surface Plasmon Resonance
D017252:CD3 Complex; D016853:Muromonab-CD3