Crystal structure of the human T cell receptor CD3εγ heterodimer complexed to the therapeutic mAb OKT3

The CD3epsilongamma heterodimer is essential for expression and function of the T cell receptor. The crystal structure of the human CD3epsilongamma heterodimer is described to 2.1-Angstrom 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 CD3epsilongamma 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 CD3epsilon. OKT3 binds to an atypically small area of CD3epsilon and has a low affinity for the isolated CD3epsilongamma heterodimer. The structure of the OKT3/CD3epsilongamma complex has implications for T cell signaling and therapeutic design.