T-cell surface glycoprotein CD3 (CD3 complex) (CD3)

The T-cell surface glycoprotein CD3 (CD3 complex) is a multisubunit signaling apparatus noncovalently associated with the T-cell receptor (TCR) on T-lymphocytes, consisting of three invariant dimers: CD3εγ, CD3εδ, and CD3ζζ, in 1:1:1:1 stoichiometry with the TCRαβ heterodimer. The TCR recognizes antigenic peptides bound to MHC (pMHC) on antigen-presenting cells, while CD3 chains transduce activation signals via immunoreceptor tyrosine-based activation motifs (ITAMs) in their cytoplasmic tails, which become phosphorylated by Lck kinase to initiate downstream cascades. Each CD3 subunit features an extracellular Ig-like domain, connecting peptide, transmembrane helix, and cytoplasmic tail (ζ chain has three ITAMs). Transmembrane helices form a compact 8-helix bundle stabilized by hydrophobic and ionic interactions. Upon pMHC ligation, conformational changes expose ITAMs from the membrane inner leaflet, enabling signaling. The complex assembles as an octameric structure with TCR at the core, critical for adaptive immunity and targeted in immunotherapies.

Other names

CD3 complexCD3εγCD3εδCD3ζζTCR-CD3 complex

ITAM phosphorylation upon TCR-pMHC binding, leading to downstream T-cell signaling cascade; antibody binding to CD3ε induces signaling or blockade