Crystal structure of the human T cell receptor CD3εγ heterodimer complexed to the therapeutic mAb OKT3
2004; National Academy of Sciences; Volume: 101; Issue: 20 Linguagem: Inglês
10.1073/pnas.0402295101
ISSN1091-6490
AutoresLars Kjer‐Nielsen, Michelle A. Dunstone, Lyudmila Kostenko, Lauren K. Ely, Travis Beddoe, Nicole A. Mifsud, Anthony W. Purcell, Andrëw G. Brööks, James McCluskey, Jamie Rossjohn,
Tópico(s)CAR-T cell therapy research
ResumoThe CD3εγ heterodimer is essential for expression and function of the T cell receptor. The crystal structure of the human CD3εγ 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 CD3εγ 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 CD3εγ heterodimer. The structure of the OKT3/CD3εγ complex has implications for T cell signaling and therapeutic design.
Referência(s)