title: Crystal structure of the human T cell receptor CD3 epsilon gamma heterodimer complexed to the therapeutic mAb OKT3.
abstract: 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.
authors.affiliation: Department of Microbiology and Immunology, University of Melbourne, Parkville, Victoria 3010, Australia.
authors.forename: Lars
authors.initials: L
authors.lastname: Kjer-Nielsen
authors.forename: Michelle A
authors.initials: MA
authors.lastname: Dunstone
authors.forename: Lyudmila
authors.initials: L
authors.lastname: Kostenko
authors.forename: Lauren K
authors.initials: LK
authors.lastname: Ely
authors.forename: Travis
authors.initials: T
authors.lastname: Beddoe
authors.forename: Nicole A
authors.initials: NA
authors.lastname: Mifsud
authors.forename: Anthony W
authors.initials: AW
authors.lastname: Purcell
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Brooks
authors.forename: James
authors.initials: J
authors.lastname: McCluskey
authors.forename: Jamie
authors.initials: J
authors.lastname: Rossjohn
mesh_terms: 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
chemical_list: D017252:CD3 Complex; D016853:Muromonab-CD3