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

Abstract

The CD3εy heterodimer is essential for expression and function of the T cell receptor. The crystal structure of the human CD3εy heterodimer is described to 2.1-Å 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 CD3εy 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 CD3ε. OKT3 binds to an atypically small area of CD3ε and has a low affinity for the isolated CD3εy heterodimer. The structure of the OKT3/CD3εγ complex has implications fo..