Crystal structure of the human T cell receptor CD3   heterodimer complexed to the therapeutic mAb OKT3 Academic Article uri icon

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

  • Kjer-Nielsen, L
  • Dunstone, MA
  • Kostenko, L
  • Ely, LK
  • Beddoe, T
  • Mifsud, NA
  • Purcell, AW
  • Brooks, AG
  • McCluskey, J
  • Rossjohn, J

publication date

  • May 18, 2004