Atomic structure of an αβ T cell receptor (TCR) heterodimer in complex with an anti-TCR Fab fragment derived from a mitogenic antibody

• Published in: The EMBO journal 1998-01, Vol.17 (1), p.10-26
• Main Authors: Wang, Jia-huai, Lim, Kap, Smolyar, Alex, Teng, Mai-kun, Liu, Jin-huan, Tse, Albert G.D., Liu, Ju, Hussey, Rebecca E., Chishti, Yasmin, Thomson, Cole T., Sweet, Robert M., Nathenson, Stanley G., Chang, Hsiu-Ching, Sacchettini, James C., Reinherz, Ellis L.
• Format: Article
• Language: English
• Subjects: crystallography; immune receptors; quaternary structure; signal transduction
• ISSN: 0261-4189; 1460-2075
• DOI: 10.1093/emboj/17.1.10

Each T cell receptor (TCR) recognizes a peptide antigen bound to a major histocompatibility complex (MHC) molecule via a clonotypic αβ heterodimeric structure (Ti) non‐covalently associated with the monomorphic CD3 signaling components. A crystal structure of an αβ TCR‐anti‐TCR Fab complex shows an Fab fragment derived from the H57 monoclonal antibody (mAb), interacting with the elongated FG loop of the Cβ domain, situated beneath the Vβ domain. This loop, along with the partially exposed ABED β sheet of Cβ, and glycans attached to both Cβ and Cα domains, forms a cavity of sufficient size to accommodate a single non‐glycosylated Ig domain such as the CD3ϵ ectodomain. That this asymmetrically localized site is embedded within the rigid constant domain module has implications for the mechanism of signal transduction in both TCR and pre‐TCR complexes. Furthermore, quaternary structures of TCRs vary significantly even when they bind the same MHC molecule, as manifested by a unique twisting of the V module relative to the C module.